Oxidative Medicine and Cellular Longevity

Oxidative Medicine and Cellular Longevity / 2019 / Article
Special Issue

Natural Products: Optimizing Cancer Treatment through Modulation of Redox Balance

View this Special Issue

Review Article | Open Access

Volume 2019 |Article ID 2075614 | https://doi.org/10.1155/2019/2075614

Paola Aiello, Maedeh Sharghi, Shabnam Malekpour Mansourkhani, Azam Pourabbasi Ardekan, Leila Jouybari, Nahid Daraei, Khadijeh Peiro, Sima Mohamadian, Mahdiyeh Rezaei, Mahdi Heidari, Ilaria Peluso, Fereshteh Ghorat, Anupam Bishayee, Wesam Kooti, "Medicinal Plants in the Prevention and Treatment of Colon Cancer", Oxidative Medicine and Cellular Longevity, vol. 2019, Article ID 2075614, 51 pages, 2019. https://doi.org/10.1155/2019/2075614

Medicinal Plants in the Prevention and Treatment of Colon Cancer

Guest Editor: Ana S. Fernandes
Received08 Mar 2019
Accepted03 Jul 2019
Published04 Dec 2019

Abstract

The standard treatment for cancer is generally based on using cytotoxic drugs, radiotherapy, chemotherapy, and surgery. However, the use of traditional treatments has received attention in recent years. The aim of the present work was to provide an overview of medicinal plants effective on colon cancer with special emphasis on bioactive components and underlying mechanisms of action. Various literature databases, including Web of Science, PubMed, and Scopus, were used and English language articles were considered. Based on literature search, 172 experimental studies and 71 clinical cases on 190 plants were included. The results indicate that grape, soybean, green tea, garlic, olive, and pomegranate are the most effective plants against colon cancer. In these studies, fruits, seeds, leaves, and plant roots were used for in vitro and in vivo models. Various anticolon cancer mechanisms of these medicinal plants include induction of superoxide dismutase, reduction of DNA oxidation, induction of apoptosis by inducing a cell cycle arrest in S phase, reducing the expression of PI3K, P-Akt protein, and MMP as well; reduction of antiapoptotic Bcl-2 and Bcl-xL proteins, and decrease of proliferating cell nuclear antigen (PCNA), cyclin A, cyclin D1, cyclin B1 and cyclin E. Plant compounds also increase both the expression of the cell cycle inhibitors p53, p21, and p27, and the BAD, Bax, caspase 3, caspase 7, caspase 8, and caspase 9 proteins levels. In fact, purification of herbal compounds and demonstration of their efficacy in appropriate in vivo models, as well as clinical studies, may lead to alternative and effective ways of controlling and treating colon cancer.

1. Introduction

An uncontrolled growth of the body’s cells can lead to cancer. Cancer of the large intestine (colon) is one of the main cause of death due to cancer. While the numbers for colon cancer are somewhat equal in women (47,820) and men (47,700), it will be diagnosed in (16,190) men (23,720) more than women. Multiple factors are involved in the development of colorectal cancer, such as lack of physical activity [1], excessive alcohol consumption [2], old age [3], family history [4], high-fat diets with no fiber and red meat, diabetes [5], and inflammatory bowel diseases, including ulcerative colitis and Crohn’s disease [6].

Prevention of colorectal cancer usually depends on screening methods to diagnose adenomatous polyps which are precursor lesions to colon cancer [7]. The standard treatment for cancer is generally based on using cytotoxic drugs, radiotherapy, chemotherapy, and surgery [8]. Apart from these treatments, antiangiogenic agents are also used for the treatment and control of cancer progression [9].

Colon cancer has several stages: 0, I, II, III, and IV. Treatment for stages 0 to III typically involves surgery, while for stage IV and the recurrent colon cancer both surgery and chemotherapy are the options [10]. Depending on the cancer stage and the patient characteristics, several chemotherapeutic drugs and diets have been recommended for the management of colorectal cancer. Drugs such as 5-fluorouracil (5-FU), at the base of the neoadjuvant therapies folfox and folfiri, are used together with bevacizumab, panitumumab, or cetuximab [7].

Chemotherapy works on active cells (live cells), such as cancerous ones, which grow and divide more rapidly than other cells. But some healthy cells are active too, including blood, gastrointestinal tract, and hair follicle ones. Side effects of chemotherapy occur when healthy cells are damaged. Among these side effects, fatigue, headache, muscle pain, stomach pain, diarrhea and vomiting, sore throat, blood abnormalities, constipation, damage to the nervous system, memory problems, loss of appetite, and hair loss can be mentioned [11].

Throughout the world, early diagnosis and treatment of cancer usually increase the individual’s chances of survival. But in developing countries, access to effective and modern diagnostic methods and facilities is usually limited for most people, especially in rural areas [12]. Accordingly, the World Health Organization (WHO) has estimated that about 80% of the world population use traditional treatments [13]. One of these treatments is phytotherapy, also known as phytomedicine, namely, the use of plants or a mixture of plant extracts for the treatment of diseases. The use of medicinal plants can restore the body’s ability to protect, regulate, and heal itself, promoting a physical, mental, and emotional well-being [1416]. Various studies have shown the therapeutic effects of plants on fertility and infertility [17], hormonal disorders, hyperlipidemia [18], liver diseases [19], anemia [20], renal diseases [21], and neurological and psychiatric diseases [22]. Therefore, due to all the positive effects showed by medicinal plants, their potential use in cancer prevention and therapy has been widely suggested [2325].

Since the current treatments usually have side effects, plants and their extracts can be useful in the treatment of colon cancer with fewer side effects. The aims of this review are to present and analyse the evidence of medicinal plants effective on colon cancer, to investigate and identify the most important compounds present in these plant extracts, and to decipher underlying molecular mechanisms of action.

2. Literature Search Methodology

This is a narrative review of all research (English full text or abstract) studies conducted on effective medicinal plants in the treatment or prevention of colon cancer throughout the world. Keywords, including colon cancer, extract, herbs, plant extracts, and plants, were searched separately or combined in various literature databases, such as Web of Science, PubMed, and Scopus. Only English language articles published until July 2018 were considered.

In the current narrative review, studies (published papers) were accepted on the basis of inclusion and exclusion criteria. The inclusion criterion was English language studies, which demonstrated an effective use of whole plants or herbal ingredients, as well as studies which included standard laboratory tests. In vivo and in vitro studies that were published as original articles or short communications were also included. The exclusion criteria included irrelevancy of the studies to the subject matter, not sufficient data in the study, studies on mushrooms or algae, and the lack of access to the full text. Reviews, case reports/case series, and letters to editors were also excluded but used to find appropriate primary literature.

The abstracts of the studies were reviewed independently by two reviewers (authors of this study) on the basis of the inclusion and exclusion criteria. In case of any inconsistency, both authors reviewed the results together and solved the discrepancy. Data extracted from various articles were included in the study and entered into a check list after the quality was confirmed. This check list included some information: authors’ name, year of publication, experimental model, type of extract and its concentration or dose, main components, and mechanisms of action (if reported).

3. Results

3.1. Medicinal Plants and Colon Cancer

Overall, 1,150 articles were collected in the first step and unrelated articles were excluded later on according to title and abstract evaluation. Moreover, articles that did not have complete data along with congress and conference proceedings were excluded. Accordingly, a total of 1,012 articles were excluded in this step. Finally, 190 articles fulfilled the criteria and were included in this review. These papers were published within 2000-2017. A total of 190 plants were included in this study. Based on literature search, 172 experimental studies and 71 clinical cases were included.

Overall, results indicate that grape, soybean, green tea, garlic, olive, and pomegranate are the most effective plants against colon cancer. In these studies, fruits, seeds, leaves, and plant roots were used for in vitro and in vivo studies.

3.1.1. In Vitro Studies

Out of 172 studies, 75 were carried out on HT-29, 60 on HCT116, and 24 on Caco-2 cells (Table 1). On HT-29 cells, both Allium sativum root extracts and Camellia sinensis leaf extracts induced cell apoptosis by two different mechanisms, respectively. In fact, the former showed inhibition of the PI3K/Akt pathway, upregulation of PTEN, and downregulation of Akt and p-Akt expression, while the latter was involved in attenuation of COX-2 expression and modulation of NFκB, AP-1, CREB, and/or NF-IL-6. Moreover, an antiproliferative activity has also been detected in Olea europaea fruit extracts, which increased caspase 3-like activity and were involved in the production of superoxide anions in mitochondria. An antiproliferative activity, by means of a blockage in the G2/M phase, has also been reported in Caco-2 cells by Vitis vinifera fruit extracts. Concerning HCT116 cells, several plants, such as American ginseng and Hibiscus cannabinus, induced cell cycle arrest in different checkpoints.


Scientific nameParts usedCell lineConc.Type of extractImportant compoundsCellular effectMechanismsReferences

Vitis viniferaFruitHCT116NMLyophilizedHydroxycinnamic acids, proanthocyanidins, stilbenoidsIncrease of dihydroceramides, sphingolipid mediators involved in cell cycle arrest, and reduction of the proliferation rate(i) Increase of p53 and p21 cell cycle gate keepers
(ii) Activation of the transcriptional factor Nrf2
[26, 27]
FruitCaco-2365 mg/gMethanolicCatechin, epicatechin, quercetin, gallic acidAntiproliferative activity and direct initiation of cell deathBlockage in the G2/M phase[28, 29]
SeedCaco-210–25 μg/mLAqueousProcyanidins(i) Increased crypt depth
(ii) Inhibited cell viability and decreased histological damage score
Reduced MPO (myeloperoxidase) activity[29]
SkinNM7.5, 30, 60 μg/mLMethanolic4-Geranyloxyferulic acidNMNM[30]
SeedColon cancer stem cells6.25, 12.5, 25 μg/mLNM(+)-catechin, (−)-epicatechinNM(i) Increment of p53, Bax/Bcl-2 ratio, and cleaved PARP
(ii) Inhibition of Wnt/β-catenin signaling
[31]

Allium sativumRootHT-2920, 50, 100 mg/mLEthanolicNMInduction of apoptosis and cell cycle arrest(i) Inhibition of the PI3K̸Akt pathway
(ii) Upregulation of PTEN and downregulation of Akt and p-Akt expression
[32]

Glycine maxSeedCaco-2, SW620, HT-2912.5 μg/mLAqueousAnthoxanthinCell death and significant reduction of cell densityEnhancement of Rab6 protein levels[33]
SeedHT-29240, 600 ppmCrudeSaponinSuppression of PKC activation and increase of alkaline phosphatase activity[33]
SeedHT-29NMCrudeSaponinNM(i) Suppression of the degradation of IκBα in PMA-stimulated cells
(ii) Downregulation of COX-2 and PKC expressions
[34]

Camellia sinensisLeafHT-290, 10, 30, 50 μMAqueousCatechin, epigallocatechin gallate1.9-fold increase in tumor cell apoptosis and a 3-fold increase in endothelial cell apoptosis(i) Suppression of ERK-1 and ERK-2 activation
(ii) Suppression of VEGF expression
[35]
LeafCaco-2, HT-29300 μMAqueousTheaflavins (TF-2T, F-3, TF-1)Human colon cancer cell apoptosis inductionModulation of NFκB, AP-1, CREB, and/or IL-6[36]
LeafHT-2968-80
0.73 μg/mL
Hot water extractFlavan-3-ol (catechin & tannin) & polyphenols (teadenol B)Inhibition of proliferation of HT-29 cellsIncreased expression levels of caspases 3/7, 8, and 9[35]

Olea europaeaFruitHT-29150, 55.5
200 and 74 μmol/L
Methanolic and chloroformMaslinic acid, oleanolic acidAntiproliferative activity(i) Increased caspase 3-like activity to 6-fold
(ii) Production of superoxide anions in the mitochondria
[37]
Fruit, leafSW480 and HT-29100–400 m/zMethanolic & hexaneOleic acid, linoleic acid, gamma-linolenic acid, lignans, flavonoids, secoiridoidsReduced cell growth in both cell lines(i) Limited G2M cell cycle
(ii) Depressed cyclooxygenase-2 expression in HT-29 cells
(iii) Suppression of β-catenin/TCF signaling in SW480 cells
(iv) Promotion of the entry into subG1 phase
[38]
FruitCaco-250 μMAqueousPhenolic compounds, authentic hydroxyl tyrosol (HT)Reduced proliferation of Caco-2 cellsReduction of the methylation levels of CNR1 promoter[39]
FruitHT11525 μg/mLHydroethanolicPhenolic compounds (p-hydroxyphenyl ethanol, pinoresinol & dihydroxyphenyl ethanol)NMInhibition by reduced expression of a range of α5 & β1[40]
Olive mill wastewaterHT-29, HCT116, CT26NMMethanolicHydroxytyrosol(i) Inhibited proliferation
(ii) Inhibited migration and invasion
(i) Reduced sprout formation
(ii) Inhibited VEGF and IL-8 levels
[41]
FruitCaco-20-2,000 μg/mLEthanolicTyrosol, hydroxytyrosol, oleuropein, rutin, quercetin and glucoside forms of luteolin and apigeninNM(i) Induction of the cell cycle arrest in S-phase[42]

Punica granatumJuiceHT-2950 mg/LAqueousEllagitannins, punicalaginInhibition of cancer cell proliferation(i) Suppressed TNFR-induced COX-2 protein expression
(ii) Reduced phosphorylation of the p65 subunit and binding to the NFκB response element
[43]
SeedLS17463.2 μg/mLSupercritical fluidPunicic acid, γ-tocopherol, α-tocopherolCytotoxic activity(i) Slightly decreased development of tubules from elongated cell bodies
(ii) Reduction of the number of cell connections
[44]

Glycyrrhiza glabraRootHT-2912.2 and 31 μg/mLEthanolicLicochalconeNMIncrease of the protein levels of proapoptotic Bax[37]

Opuntia ficus-indicaFruitCaco-2115 μMAqueousBetalain pigment indicaxanthinApoptosis of proliferating cells(i) Demethylation of the tumor suppressor p16INK4a gene promoter
(ii) Reactivation of the silenced mRNA expression and accumulation of p16INK4a
[38]
FruitHT-29 & Caco-2 & NIH 3 T3 (as control)Against HT-29 (4.9 μg/mL) against Caco-2 (8.2 μg/mL)Alkaline hydrolysis with NaOHIsorhamnetin glycosides (IG5 and IG6)-phenolCell death through apoptosis and necrosisIncreased activity of caspase 3/7[45]

Piper betleLeafHT-29 and HCT116200.0 μg/mLAqueousHydroxychavicolAntioxidant capacity and induction of a greater apoptotic effect(i) Scavenging activity
(ii) Formation of electrophilic metabolites
[41, 46]

Fragaria×ananassaFruitHT-290.025, 0.05, 0.25, 0.5%EthanolicAscorbate, ellagic acidDecreased proliferation of HT-29 cellsIncrease in the levels of 8OHA and decrease in the levels of 8OHG[40]

Sasa quelpaertensisLeafHT-29 HCT1160, 100, 200, 300 mg/LEthanolicp-Coumaric acid, tricinInhibited colony formationNonadherent sphere formation suppressed CD133+ & CD44+ population[41]

Salvia chinensisStemHCT116, COLO 20510, 20, 40,60, 80, 100 mg/LPolyphenolicTerpenoids, phenolic acid, flavonoids, dibenzylcyclooctadieneApoptosis & loss of mitochondrial membraneInduced G0/G1 cell cycle[42]

Rubus idaeus L.FruitHT-29, HT-115, Caco-23.125, 6.25, 12.5, 25, 50 mg/LAcetatePolyphenol, anthocyanin, ellagitanninNMDecreased population of cells in G1 phase[47]
LoVo50 μLAqueousNMInhibited proliferation of LoVoSuppression of the NFκB pathway[48]

Curcuma longaRootHT-29, HCT15, DLD1, HCT116(i) Short-term assay: four 10-fold dilutions (100 to 0.1 mg/L)
(ii) Long-term assay: 5, 10, 20 mg/L
EthanolicCurcumin (diferuloylmethane)Inhibited formation of HCT116 spheroidsNM[49]

Eleutherococcus senticosusRootHCT11612.5, 25, 50, 100MethanolicEleutherosides, triterpenoid saponins, glycansNMActivation of natural killer cells and thus enhancement of immune function[50]

Tabernaemontana divaricata L.LeafHT-29, HCT1510, 30, 100 mg/LEthyl acetate, chloroform, methanolicAlkaloidsNMInhibited the unwinding of supercoiled DNA[45]

Millingtonia hortensisRoot, flower, leafRKO50, 100, 200, 400, 800 mg/LAqueousPhenylethanoid glycoside, squalene, salidroside, 2-phenyl rutinosideApoptosis induction(i) Increase of fragmented DNA
(ii) Decrease of the expression of antiapoptotic proteins, Bcl-xL and p-BAD
[46]
PowderRKO200, 400, 800 μg/mLAqueousWater soluble compoundsAntiproliferative effectNM[51]

Thai purple riceSeedCaco-2, Cat. No. HTB-3716.11 μg/mLMethanol acidifiedCyanidin-3-glucoside and peonidin-3-glucoside, anthocyanins, phenolic compounds(i) Antioxidation of anthocyanins and phenols
(ii) Antiproliferation of colon cancer cells
NM[52]

Annona muricataLeafHCT116, HT-29 and EthanolicAlkaloids, acetogenins, essential oilsBlock of the migration and invasion of HT-29 and HCT116 cells(i) Cell cycle arrest at G1 phase
(ii) Disruption of MMP, cytochrome c leakage and activation
[53]
NMHT-29, HCT116<4, <20 μg/mLEtOAcAnnopentocin A, annopentocin B, annopentocin C, cis- and trans-annomuricin-D-ones, annomuricin ENMSuppression of ATP production and NADH oxidase in cancer cells[54]

Pistacia lentiscus L. var. chiaLeafHCT116NMEthanolicResin, known as Chios mastic gum (CMG)Causes several morphological changes typical of apoptosis in cell organelles(i) Induction of cell cycle arrest at G1 phase
(ii) Activation of pro-caspases 8, 9, 3
[55]
ResinHCT116100 μg/mLHexaneCaryophylleneInduction of the anoikis form of apoptosis in human colon cancer HCT116 cells(i) Induction of G1 phase arrest
(ii) Loss of adhesion to the substrate
[56]

American ginseng (Panax quinquefolius)Biological constituentsHCT1160-2.0 mg/mLAqueousGinseng (GE) or its ginsenoside (GF) and polysaccharide (PS)Proliferation was inhibited by GE, GF, and PS in wild-type and p21 cells(i) Cells arrest in G0/G1 phase and increment of p53 and p21 proteins
(ii) Increment of Bax and caspase 3 proteins expression
[57]

Purple-fleshed potatoesFruitColon cancer stem cells5.0 μg/mLEthanol, methanol, ethyl acetateAnthocyanin, β-catenin, cytochrome cCritical regulator of CSC proliferation and its downstream proteins (c-Myc and cyclin D1) and elevated Bax and cytochrome c(i) Cytochrome c levels were elevated regardless of p53 status
(ii) Mitochondria-mediated apoptotic pathway
(iii) Suppressed levels of cytoplasmic and nuclear β-catenin
[58]

Phaseolus vulgarisLeafHT-29NMEthanolicPolysaccharides, oligosaccharidesChanges in genes involved or linked to cell cycle arrest(i) Inactivation of the retinoblastoma phosphoprotein
(ii) Induction of G1 arrest
(iii) Suppression of NF-jB1
(iv) Increase in EGR1 expression
[59]

Opuntia spp.FruitHT-29, , ()HydroalcoholicBetacyanins, flavonoids (isorhamnetin derivatives) and phenolic acids (ferulic acid)NMInduced cell cycle arrest at different checkpoints—G1, G2/M, and S[60]

Suillus luteusNMHCT15400 μg/mLMethanolicProtocatechuic acid, cinnamic acid, α-tocopherol, β-tocopherol, mannitol, trehalose, polyunsaturated fatty acids, monounsaturated fatty acids, saturated fatty acids(i) Increase in the cellular levels of p-H2A.X, which is suggestive of DNA damage(i) Inhibition of cell proliferation in G1 phase
(ii) Increase in the cellular levels of p-H2A.X
[61]

Poncirus trifoliataLeafHT-290.63 μMAqueous (in acetone)β-Sitosterol, 2-hydroxy-1,2,3-propanetricarboxylic acid 2-methyl esterArrest of cell growth was observed with β-sitosterolNM[62]

Rosmarinus officinalis L.LeafSW 620, DLD-10-120 μg/mLMethanolicPolyphenolsAntiproliferative effect of 5-FUDownregulation of TYMS and TK1, enzymes related to 5-FU resistance[63]
LeafHT-29SC-RE 30 μg/mL and CA 12.5 μg/mLEthanolicPolyphenols (carnosic acid (CA) and carnosol)(i) Upregulation of VLDLR gene as the principal contributor to the observed cholesterol accumulation in SC-RE-treated cells
(ii) Downregulation of several genes involved in G1-S
Activation of Nrf2 transcription factor and common regulators, such as XBP1 (Xbp1) gene related to the unfolded protein response (UPR)[64]
NMHT-2910, 20, 30, 40, 50, 60, 70 μg/mLNMCarnosic acid, carnosol, rosmarinic acid, rosmanolNMNM[65]
LeafHGUE-C-1, HT-29, and SW48020–40 mg/mLCO2-supercritical fluid extractCarnosic acid, carnosol, and betulinic acidNM(i) Prooxidative capability by increasing the intracellular generation of ROS
(ii) Activation of Nrf2
[66]

Glehnia littoralisLeafHT-2950 mg/mLMethanolicBergapten, isoimpinellin, xanthotoxin, imperatorin, panaxydiol, falcarindiol, falcarinolInduced apoptosis by the decreased expression of the antiapoptotic Bcl-2 mRNA(i) Reduced expression of Bcl-2
(ii) Reduced expression levels of iNOS and COX-2
[67]

Verbena officinalisLeafHCT11620 mg/mLAqueousPhenylethanoid glycosides, diacetyl-O-isoverbascoside, diacetyl-O-betonyoside A, and diacetyl-O-betonyoside A(i) Substantial tumor cell growth inhibitory activity
(ii) Time-dependent cytotoxicity against both cell lines
(i) Increased lipophilicity of molecules seemed to be responsible for enhanced cytotoxicity
(ii) Antiproliferative activity is determined by the number of acetyl groups and also by their position in the aliphatic rings
[68]

Mentha spicataLeafRCM-112.5 μg/mLN-HexaneAcetic acid 3-methylthio propyl ester (AMTP), methyl thio propionic acid ethyl ester (MTPE)Exhibited antimutagenic activityAuraptene (7-geranyloxycoumarin) having a monoterpene moiety and β-cryptoxanthin (one of the tetraterpenes) increased antibody production[69]

Euphoria longana Lam.SeedSW 4800–100 μg/mLEthanolicCorilagin, gallic acid, ellagic acid(i) Antiangiogenetic properties
(ii) All fractions showed the anti-VEGF secretion activity
Release and expression of VEGF indicated that all fractions showed the anti-VEGF secretion activity[70]

Sutherlandia frutescensFlowerCaco-21/50 dilution of the ethanolic extractEthanolicAmino acids, including L-arginine and L-canavanine, pinitol, flavonoids, and triterpenoid saponins as well as hexadecanoic acid and γ-sitosterolDisruption of the key molecules in the PI3K pathway thereby inducing apoptosisDecrease in cell viability and increment in pyknosis as well as loss in cellular membrane integrity[71]

Melissa officinalisLeafHT-29, T84346, 120 μg/mLEthanolicPhenolic acids (rosmarinic acid, coumaric acid, caffeic acid, protocatechuic acid, ferulic acid, chlorogenic acid), flavonoids, sesquiterpenes, monoterpenes, triterpenes(i) Inhibited proliferation of colon carcinoma cells
(ii) Induced apoptosis through formation of ROS
(i) G2/M cell cycle arrest
(ii) Cleavage of caspases 3 and 7
(iii) Induced phosphatidylserine externalization in colon carcinoma cells
(iv) Induced formation of ROS in colon carcinoma cells
[72]

Sargassum cristaefoliumLeafHT-29500 mg/mLEthanolicFucoidans(i) Reduction of free radicals
(ii) DPPH radical scavenging
Accumulation of cells in G0/G1 phase[73]

Hedyotis diffusaNMHT-29400 mg/mLEthanolic and then DMSOOctadecyl (E)-p-coumarate, P-E-methoxy-cinnamic acid, ferulic acid, scopoletin, succinic acid, aurantiamide acetate, rubiadinSuppress tumor cell growth and induce the apoptosis of human CRC cells(i) Block G1/S progression
(ii) Induce the activation of caspases 9 and 3
(iii) Inhibit IL-6-mediated STAT3 activation
(iv) Downregulate the mRNA and protein expression levels of cyclin D1, CDK4, Bcl-1, and Bax
[74]

Zingiber officinale RoscoePeelLoVo100 mg/mLEthanolicLinoleic acid methyl ester, α-zingiberene, and zingiberoneInteresting antiproliferative activity against colorectal carcinomaNM[75]

Scutellaria barbataLeafLoVo413.3 mg/LMethanolicScutellarein, scutellarin, carthamidin, isocarthamidin, wogoninInduce cell death in the human colon cancer cell lineIncrease in the sub-G1 phase and inhibition of cell growth[76]

Pistacia atlantica, Pistacia lentiscusResinHCT116100 μg/mLHexane extractCaryophylleneInduce the anoikis form of apoptosis in human colon cancer HCT116 cells(i) Induce G1 phase arrest
(ii) Loss of adhesion to the substrate
[56]

Citrus reticulataPeelSNU-C4100 μg/mLMethanolicLimonene, geranial, neral, geranyl acetate, geraniol, β-caryophyllene, nerol, neryl acetateInduce the apoptosis on SNU-C4, human colon cancer cellsExpression of proapoptotic gene, Bax, and major apoptotic gene, caspase 3[77]

Echinacea pallida, Echinacea angustifolia, Echinacea purpureaRootCOLO320150 mg/mLHexanicCaffeic acid derivatives, alkylamides, polyacetylenes, polysaccharidesInduce apoptosis and promote nuclear DNA fragmentation(i) Induce apoptosis by increasing caspase 3/7 activity
(ii) Promote nuclear DNA fragmentation
[78]

Nasturtium officinaleLeafHT-2950 μL/mLMethanolicPhenethyl isothiocyanate, 7-methylsulfinylheptyl, 8-methylsulfinyl(i) Inhibition of initiation, proliferation, and metastasis(i) Inhibited DNA damage
(ii) Accumulation of cells in S phase of the cell cycle
[79]

PolysiphoniaNMSW480, HCT15, HCT116, DLD-120 and 40 μg/mLMethanolic2,5-Dibromo-3,4-dihydroxybenzyl n-propyl etherPotentially could be used as a chemopreventive agent against colon cancer(i) Inhibited Wnt/β-catenin pathway
(ii) Repressed CRT in colon cancer cells
(iii) Downregulated cyclin D1
(iv) Activated the NFκB pathway
[80]

Aristolochia debilis Sieb. et Zucc.StemHT-29200 μg/mLMethanolicAristolochic acid, nitrophenanthrene carboxylic acidsInhibition of proliferation and induction of apoptosis in HT-29 cells(i) Induction of sub-G1 cell cycle
(ii) Generation of ROS and decrease of the MMP
(iii) Bax overexpression and increase of Bax/Bcl-2 ratio
[81]

MyrtaceaeLeafHCT116100 μg/mL (in vitro), 200 and 100 μg/disc (in vivo)MethanolicPhenols, flavonoid, betulinic acidStrong inhibition of microvessel outgrowth(i) Inhibition of tube formation on Matrigel matrix
(ii) Inhibition of HUVECS migration (in vitro)
(iii) Decreased nutrient and oxygen supply
[82]

Spica prunellaeLeafHT-29200 mg/mL (in vitro), 600 mg/mL (in vivo)EthanolicRosmarinic acidInhibits CRC cell growth(i) Suppresses STAT3 phosphorylation
(ii) Regulates the expression of Bcl-2, Bax, cyclin D1, CDK4, VEGF-A, and VEGFR-2
[83]

Phytolacca americanaRootHCT1163200 μg/mLEthanolicJaligonic acids, kaempferol, quercetin, quercetin 3-glucoside, isoquercitrin, ferulic acidControl of growth and spread of cancer cellsReduction in the expressions of MYC, PLAU, and TEK[84]

Morus albaLeafHCT1513.8 μg/mLMethanolicEpicatechin, myricetin, quercetin hydrate, luteolin, kaempferol, ascorbic acid, gallic acid, pelargonidine, p-coumaric acidCytotoxic effect on human colon cancer cells (HCT15)(i) Apoptosis induction also involved in the downregulation of iNOS
(ii) Fragmentation of DNA
(iii) Upregulation of caspase 3 activity
[85]

Rhodiola imbricataLeafHT-29200 μg/mLAcetone and methanolicPhenols, tannins, and flavonoids(i) Antioxidant activity
(ii) Inhibited proliferation of HT-29 cells
(i) Scavenge free radicals
(ii) DPPH radical scavenging activity
(iii) Increased metal chelating activity
[86]

Asiasarum heterotropoides F.Dried A. radixHCT11620 mg/mLEthanolicAsarinin and xanthoxylolInhibition of the growth of HCT116 cells(i) Caspase-dependent apoptosis
(ii) Regulation of p53 expression at transcription level
[87]

Podocarpus elatusFruitHT-29500 mg/mLMethanolicPhenolic and anthocyaninReduction of proliferation of colon cancer cells(i) Cell cycle delay in S phase
(ii) 93% downregulation of telomerase activity and decrease in telomere length
(iii) Induced morphological alterations to HT-29 cells
[88]

Echinacea purpureaFlowerCaco-2, HCT1160–2,000 mg/mLHydroethanolicCichoric acid(i) Inhibition of proliferation
(ii) Decreased telomerase activity in HCT116 cells
(i) Decreased telomerase activity
(ii) Activation of caspase 9
(iii) Cleavage of PARP
(iv) Downregulation of β-catenin
[89]
RootCOLO320150 mg/mLHexanicCaffeic acid derivatives, alkylamides, polyacetylenes, polysaccharidesInduce apoptosis by increasing significantly caspase 3/7 activity and promote nuclear DNA fragmentation(i) Increase significantly caspase 3/7 activity
(ii) Promote nuclear DNA fragmentation
[78]

Hop (Humulus lupulus L.), Franseria artemisioidesLeafNM100 mg/kg b.w./dayAqueousCoumarin, lignans, quinones30% reduction of tumor-induced neovascularizationNM[90]
NMCaco-2NMEthanolicPhenolic compounds, flavonoid, diterpenesDigestive, gastroprotective, antiseptic, anti-inflammatory, and antiproliferative activityNM[91]
FruitNL-170, 50, 100, 150 μg/mLMethanolicα-Mangostin (xanthone)NM(i) Induction of caspase 3 and caspase 9 activation
(ii) Induced cell cycle arrest at G1/G0 phase
[92]
Stem, barkHT-2950 μg/mLChloroform-solubleβ-Mangostin, garcinone D, cratoxyxanthoneCytotoxic activity against HT-29 human colon cancerInhibition of p50 and p65 activation[93]

Annona squamosa LinnLeafHCT1168.98 μg/mLCrude, Aq ethyl acetateAcetogenins (annoreticuin & isoannoreticuin) and alkaloids dopamine, salsolinol, and coclaurineInhibition of growth and proliferation of tumor cells(i) Reactive oxygen species (ROS) formation, lactate dehydrogenase (LDH) release
(ii) Activation of caspases 3/7, 8, and 9
[94]

Derris scandensStemHT-295-15 μg/mLEthanolicBenzyls and isoflavones (genistein, coumarins, scandinone)Apoptosis and mitotic catastrophe of human colon cancer HT-29 cells(i) Inhibition of α-glucosidase activity
(ii) Scavenge free radicals
[95]

Eupatorium cannabinumAerial partsHT-2925 μg/mLEthanolicPyrrolizidine alkaloids (senecionine, senkirkine, monocrotaline, echimidine)Induced alteration of colony morphology(i) Upregulation of p21 and downregulation of NCL, FOS, and AURKA
(ii) Mitotic disruption and nonapoptotic cell death via upregulation of Bcl-xL, limited TUNEL labeling, and nuclear size increase
[96]

Sorghum bicolorThe dermal layer of stalkHCT116 & colon cancer stem cells>16 and 103 μg/mLPhenolic-rich ethanolic, acetoneApigeninidin & luteolinidinAntiproliferativeTarget p53-dependent and p53-independent pathways[97]
Dermal and seed headCCSCNMMethanolicApigeninidin, luteolinidin, malvidin 3-O-glucoside, apigenin, luteolin, naringenin, naringenin 7-O-glucoside, eriodictyol 5-glucoside, taxifolin, catechinsNM(i) Elevation of caspase 3/7 activity
(ii) Decrease in β-catenin, cyclin D1, c-Myc, and survivin protein levels
(iii) Suppression of Wnt/β-catenin signaling in a p53-dependent (dermal layer) and partial p53-dependent (seed head) manner
[98]

Hibiscus cannabinusSeedHCT116KSE (15.625 μg/mL to 1,000 μg/mL)EthanolicGallic acid, p-hydroxybenzoic acid, caffeic acid, vanillic acid, syringic acid, and p-coumaric and ferulic acidsCytotoxic activity against human colon cancer HCT116 cellsApoptosis via blockade of mid G1-late G1-S transition thereby causing G1 phase cell cycle arrest[99]

Salix aegyptiaca L.BarkHCT116 & HT-29300 μg/mLEthanolicCatechin, salicin, catechol and smaller amounts of gallic acid, epigallocatechin gallate (EGCG), quercetin, coumaric acid, rutin, syringic acid, and vanillinAnticarcinogenic effects in colon cancer cellsApoptosis via inhibition of phosphatidylinositol 3-kinase/protein kinase B and mitogen-activated protein kinase signaling pathways[100]

Rubus coreanumFruitHT-29400 μg/mLAqueousPolyphenols, gallic acid, sanguineInduction of apoptosis(i) Induced activity of caspases 3, 7, and 9
(ii) Cleavage of poly(adenosine diphosphate-ribose) polymerase
[101]

Codonopsis lanceolataRootHT-29200 μg/mLN-Butanol fractionTannins, saponins, polyphenolics, alkaloidsApoptosis in human colon tumor HT-29 cells(i) Induced G0/G1 arrest
(ii) Enhancement of expression of caspase 3 and p53 and of the Bax/Bcl-2 ratio
[102]

Gleditsia sinensisThornHCT116800 μg/mLAqueousFlavonoid, lupine acid, ellagic acid glycosides(i) Increase in p53 levels
(ii) Downregulation of the checkpoint proteins, cyclin B1, Cdc2, and Cdc25c
Inhibition of proliferation of colon cancer cells[90]
ThornHCT116600 μg/mLEthanolicNMInhibitory effect on proliferation of human colon cancer HCT116 cells(i) Caused cell cycle arrest at G2/M phase together with a decrease of cyclin B1 and Cdc2
(ii) Progression from G2/M phase
[91]

Ligustrum lucidumFruitDLD-150 μg/mLAqueousOleanolic acid, ursolic acidInhibited proliferation(i) Reduction of Tbx3 rescued the dysregulated P14ARF-P53 signaling[94]

Zingiber officinaleRhizomeHCT1165 μMEthanolic6-Paradol, 6- and 10-dehydrogingerdione, 6- and 10-gingerdione, 4-, 6-, 8-, and 10-gingerdiol, 6-methylgingerdiol, zingerone, 6-hydroxyshogaol, 6-, 8-, 10-dehydroshogaol, diarylheptanoidsInhibitory effects on the proliferation of human colon cancer cells(i) Arrest at G0/G1 phase
(ii) Reduced DNA synthesis
[103]

Grifola frondosaFruitHT-2910 ng/mLAqueousPhenolic compounds (pyrogallol, caffeic acid, myricetin, protocatechuic acid)Inhibition of TNBS-induced rat colitisInduced cell cycle progression in G0/G1 phase[104]

Cucumaria frondosaThe enzymatically hydrolyzed epithelium of the edibleHCT116<150 μg/mLHydroalcoholicMonosulphated triterpenoid glycoside frondoside A, the disulphated glycoside frondoside B, the trisulphated glycoside frondoside CInhibition of human colon cancer cell growth(i) Inhibition at S and G2-M phases with a decrease in Cdc25c and increase in p21WAF1/CIP
(ii) Apoptosis associated with H2AX phosphorylation and caspase 2
[105]

Rolandra fruticosaLeaf & twigsHT-2910 and 5 mg/kg/dayMethanolicSesquiterpene lactone (13-acetoxyrolandrolide)Antiproliferative effect against human colon cancer cellsInhibition of the NFκB pathway, NFκB subunit p65 (RelA), upstream mediators IKKβ and oncogenic K-ras[106]

Cydonia oblonga MillerLeaf & FruitCaco-2250–500 μg/mLMethanolicPhenolic compound (flavonol and flavone heterosides, 5-O-caffeoylquinic acid)Antiproliferative effect against human kidney and colon cancer cells(i) Suppression of factor activation, nuclear factor-kB (NFκB) activation, protein-1 (AP-1) transcription factor, mitogen protein kinases (MAPKs), protein kinases (PKs), namely, PKC, growth-factor receptor- (GFR-) mediated pathways and angiogenesis
(ii) Cell cycle arrest and induction of apoptosis, antioxidant, and anti-inflammatory effects
[107]

Morchella esculentaFruitsHT-29820 mg/mLMethylene chlorideSteroids (mainly ergosterol derivatives) & polysaccharides & galactomannanAntioxidant activity in HT-29 colon cancer cellsInhibition of NF-B activation in the NF-B assay[108]

Sedum kamtschaticumAerial partHT-290–0.5 mg/mLMethanolicBuddlejasaponin IVInduced apoptosis in HT-29 human colon cancer cellsInduction of apoptosis via mitochondrial pathway by downregulation of Bcl-2 protein levels, caspase 3 activation, and subsequent PARP cleavage[109]

Ginseng and Glycyrrhiza glabraLeafHT-29500 μLAqueousUracil, adenine, adenosine, Li-glycyrrhetinic acid, quiritinNMAntiproliferative effect determination of the protein levels of p21, cyclin D1, PCNA, and cdk-2, which are the key regulators for cell cycle progression[110]

Orostachys japonicusLeaf & stemHT-292 mg/mLAqueousFlavonoids, triterpenoids, 4-hydroxybenzoic acid, 3,4-dihydroxybenzoic acid, polysaccharideAntiproliferation in HT-29 colon cancer cellsInhibited proliferation at G2 point of the cell cycle and apoptosis via tumor suppressor protein p53[111]

Ginkgo bilobaFruit & leafHT-2920–320mg/LAqueousTerpene lactones and flavonoid glycosides(i) Inhibited progression of human colon cancer cells
(ii) Induced HT-29 cell apoptosis
Increase in caspase 3 activities and elevation in p53 MRN reduction in Bcl-2 mRNA[112]

Oryza sativaSeedHT-29, SW 480, HCEC100 μg/mLEthyl acetatePhenolic compound (tricin, ferulic acid, caffeic acid, and methoxycinnamic acid)Inhibition of the human colon cancer cell growth(i) Induced apoptosis by enhanced activation of caspases 8 and 3
(ii) Decrease of the number of viable SW480 and HCEC cells
(iii) Reduced colony-forming ability of these cells
[113]

Cnidium officinale MakinoRootHT-29305.024/mLEthanolicOsthole, auraptenol, imperatorinInhibited proliferation of human colon cancer cells (HT-29)Inhibition of the cellular proliferation via G0/G1 phase arrest of the cell cycle and induced apoptosis[114]

Cnidium officinale MakinoRootHT-290.1-5 mg/mLAqueousN-(3-(Aminomethyl)benzyl)acetamidineInhibited the invasiveness of cytokine-treated HT-29 cells through the Matrigel-coated membrane in a concentration-dependent manner(i) Reduction of HT-29 cell invasion through the Matrigel
(ii) Inhibited cytokine-mediated NO production, iNOS expression, and invasiveness of HT-29 cells
(iii) Inhibited MMP-2 activity
[115]

Long pepper (PLX)FruitHT-29 and HCT1160.10 mg/mLEthanolicPiperidine alkaloids, piperamides, piperlongumine(i) Induction of apoptosis, following DNA fragmentation in HT-29 colon cancer cells in a time-dependent manner
(ii) Induced caspase-independent apoptosis
Induced whole cell ROS production[116]

Achyranthes asperaRootCOLO 20550-100 and 150-200 μg/mLEthanolic (EAA) and aqueous (AAA) root extracts
Aqueous
Phenolic compounds(i) Enhanced growth inhibitory effects of AAA towards COLO 205 cells in contrast to EAA
(ii) Stimulatory role of AAA in the activation of cell cycle inhibitors
(i) Triggered mitochondrial apoptosis pathway and S phase cell cycle arrest
(ii) Increased levels of caspase 9, caspase 3, and caspase 3/7 activity
[117]

Thymus vulgarisLeafHCT1160.2, 0.4, 0.6, 0.8 mg/mLCarvacrol and thymolInhibited proliferation, adhesion, migration, and invasion of cancer cells[118]

Dictyopteris undulataNMSW48040 μg/mLEthanolicCyclozonarone benzoquinoneNMInduced apoptosis by reducing Bcl-2 levels, upregulating Bax, and disrupting the mitochondrial membrane potential, leading to the activation of caspases 3 and 9[119]

Dendrobium microspermaeNMHCT1160.25, 0.5, 1.0 mg/mLMethanolicNMNMUpregulation of Bax and caspases 9 and 3 and downregulation of Bcl-2 expression of genes[120]

Cannabis sativaDry flower & leafDLD-1 and HCT1160.3–5 μMMethanolicCannabidiol, phytocannabinoidsReduced cell proliferation in a CB1-sensitive(i) Reduced AOM-induced preneoplastic lesions and polyps
(ii) Inhibited colorectal cancer cell proliferation via CB1 and CB2 receptor activation
[121]

Phoenix dactylifera L.FruitCaco-20.2 mg/mLAqueousPhenolic acids (gallic, protocatechuic, hydroxybenzoic, vanillic, isovanillic, syringic, caffeic, ferulic, sinapic, p-coumaric, isoferulic), flavonoid glycosides (quercetin, luteolin, apigenin, and kaempferol), and anthocyanidinsIncreasing beneficial bacterial growth and inhibition of proliferation of colon cancer cellsNM[122]

Melia toosendanFruitSW480, CT260, 10, 20, 30, 40, 50 μg/mLEthanolicTriterpenoids, flavonoids, polysaccharide, limonoidsNM(i) Inhibited cell proliferation of SW480 and CT26 by promoting apoptosis as indicated by nuclear chromatin condensation and DNA fragmentation
(ii) Induced caspase 9 activity which further activated caspase 3 and poly(ADP-ribose) polymerase cleavage, leading the tumor cells to apoptosis
[123]

Crocus sativus L.FlowerHCT1160.25, 0.5, 1, 2, 4 μg/mLEthanolicCarotenoid, pigment, crocin, crocetinInduced DNA damage and apoptosis(i) Induction of a p53 pattern-dependent caspase 3 activation with a full G2/M stop
(ii) Induced remarkable delay in S/G2 phase transit with entry into mitosis
[124]
Tepals and leafCaco-20.42 mg/mLNMPolyphenols, glycosides of kaempferol, luteolin, and quercetinProliferation of Caco-2 cells was greatly inhibitedNM[125]

Luffa echinataFruitHT-2950, 100, and 200 μg/mLMethanolicAmariin, echinatin, saponins, hentriacontane, gypsogenin, cucurbitacin B, datiscacin, 2-O-β-D-glucopyranosyl cucurbitacin B, and 2-O-β-D-glucopyranosyl cucurbitacin SIncrease in the population of apoptotic cells(i) Inhibited the cellular proliferation of HT-29 cells via G2/M phase arrest of the cell cycle
(ii) Induced apoptotic cell death via ROS generation
(iii) Accumulation of caspase 3 transcripts of HT-29 cells
[126]

Vitis aestivalis hybridFruits (wine)CCD-18Co25, 50, 100 μg/mLNMPolyphenolicsNM(i) Decreased mRNA expression of lipopolysaccharide- (LPS-) induced inflammatory mediators NFκB, ICAM-1, VCAM-1, and PECAM-1
(ii) Enhanced expression of miR-126
(iii) Decreased gene expression and reduced activation of the NFκB transcription factor, NFκB-dependent
(iv) Decrease in ROS 113MAH
[127]

Xylopia aethiopicaDried fruitHCT1160, 5, 10, 15, 20, 25, 30 μg/mLEthanolicEnt-15-oxokaur-16-en-19-oic acid (EOKA)NM(i) Induced DNA damage, cell cycle arrest in G1 phase, and apoptotic cell death[128]

SorghumGrainER-β; nonmalignant young adult mouse colonocytes1, 5, 10, 100 μg/mLAqueousFlavones (luteolin and apigenin), 3-deoxyanthocyanins naringenin (eriodictyol and naringenin)Reduced cell growth via apoptosisIncreased caspase 3 activity[129]
NMHT-29, HCT1160.9-2.0 mg/mLHydroethanolicProcyanidin B1, delphinidin-3-O-glucoside, tannin, cyanidin-3-O glucoside(i) Significantly arrested HT-29 cells in G1
(ii) Highest growth inhibition
(iii) Increased percentage of apoptotic cells
(i) Downregulation of apoptotic proteins, such as cIAP-2, livin, survivin, and XIAP, was seen in HCT116 cells
(ii) Inhibition of tyrosine kinase
[130]

Panax notoginseng (Burk.) F.H. ChenRootLoVo and Caco-20, 100, 250, and 500 μg/mLAlcoholicSaponin, ginsenosideNMDelay in progression of the G0/G1, S, or G2/M cell cycle phases[131]

Brassica oleracea L. var. italicaBroccoli floretsHCT1160, 1, 2.5, 5, 10 μg/mLEthanolicGlucoiberin, 3 hydroxy,4(α-L-rhamnopyranosyloxy), benzyl glucosinolate 4-vinyl-3-pyrazolidinone 4-(methyl sulphinyl), butyl thiourea, β-thioglucoside N-hydroxysulphatesNMNM[132]

Cistanche deserticolaDried stemSW480In vivo: 0.4 g/kg/day
In vitro: 100 μg/mL
AqueousPolysaccharides, phenylethanoid glycosides(i) Decreased number of mucosal hyperplasia and intestinal helicobacter infection
(ii) Increased number of splenic macrophage, NK cells, and splenic macrophages
Decreased frequency of hyperplasia and Helicobacter hepaticus infection of the intestine[133]

Chaenomeles japonicaFruitCaco-2 and HT-2910, 25, 50, 75, 100, 125, 150 μM CENMProcyanidinsNMNM[134]

Prunus mumeFruitSW480, COLO, and WiDr150, 300, and 600 μg/mLHydrophobicTriterpenoid saponinsNM(i) Inhibited growth and lysed SW480, COLO, and WiDr
(ii) Induction of massive cytoplasmic vacuoles
[135]

Solanum lyratumNMCOLO 20550, 100, 200, 300, 400 μg/mLEtOHβ-LycotetraosylInduced S phase arrest and apoptosis(i) Induced DNA fragments
(ii) Increased the levels of p27, p53, cyclin B1, active-caspase 3, and Bax
(iii) Decreased the levels of Cdk1, pro-caspase 9, Bcl-2 and NF-ÎB, p65, and p50
[136]

Onopordum cynarocephalumAerial partsHCT116, HT-290, 0.04, 0.12, 0.2, 0.4, 1.2 mg/mL
0, 0.2, 0.4, 1.2, 2.0, 3.0 mg/mL
AqueousFlavonoids, lignans, and sesquiterpene lactonesNM(i) Increase in the expression of proapoptotic proteins such as p53, p21, and Bax
(ii) Inhibition of the antiapoptotic protein Bcl-2
(iii) Decrease in cyclin D1 protein
[137]

Eleutherine palmifoliaBulbsSW4802.5, 5, 10 μg/mLMeOHEleutherin, isoeleutherinNM(i) Inhibited the transcription of TCF/β-catenin
(ii) Decrease in the level of nuclear β-catenin protein
[138]

Asparagus officinalisSpearsHCT11676 μg/mLAcetoneSteroidal saponins (HTSA-1, HTSAP-2, HTSAP-12, HTSAP-6, HTSAP-8)NM(i) Inhibition of Akt, p70S6K, and ERK phosphorylation
(ii) Induction of caspase 3 activity, PARP-1 cleavage, DNA fragmentation, G0/G1 cell cycle arrest by reducing the expression of cyclins D, A, and E
[139]

Phyllanthus emblica L.Seed, pulpHCCSCs, HCT116200 μg/mLMethanolicTrigonelline, naringin, kaempferol, embinin, catechin, isorhamnetin, quercetin(i) Suppressed proliferation
(ii) Induced apoptosis independent from p53 stemness property (in HCCSCs)
(iii) Antiproliferative properties
(i) Suppressed cell proliferation and expression of c-Myc and cyclin D1
(ii) Induced intrinsic mitochondrial apoptotic signaling pathway
[140]

Red grapeNMHT-29, HCT1160.9-2.0 mg/mLHydroethanolicDelphinidin glycosides, quercetin derivatives, delphinidin-3-O-glucoside (high), cyanidin-3-O-glucoside(i) Highest growth inhibition
(ii) Increased the percentage of apoptotic cells
(i) Downregulation of apoptotic proteins, such as cIAP-2, livin, survivin, and XIAP
(ii) Inhibition of tyrosine kinase
[130]

Black lentilNMHT-29, HCT1160.9-2.0 mg/mLHydroethanolicDelphinidin glycosides, procyanidin B1, delphinidin-3-O-glucoside (high), cyanidin-3-O-glucoside(i) Significantly arrested HT-29 cells in G1
(ii) Highest growth inhibition
(iii) Increased percentage of apoptotic cells
(i) Downregulation of apoptotic proteins, such as cIAP-2, livin, survivin, and XIAP
(ii) Inhibition of tyrosine kinase
[130]

Graptopetalum paraguayenseLeafCaco-2, BV-20.2, 0.4, 0.6, 0.8, 1.0 mg/mLHydroethanolicOxalic acid, hydroxybutanedioic acid, gallic acid, quercetin, chlorogenic acid glucans with fucose, xylose, ribose (GW100) arabino-rhamnogalactans (GW100E)(i) Great potential in antiproliferation
(ii) Significant immunomodulatory activities on BV-2 cells and interleukin-6 (IL-6) (GW100)
(i) Scavenging α, α-diphenyl-β-picrylhydrazyl radicals (DPPH) (GW100E excelled in scavenging DPPH), 2,2-azino-bis [3-ethylbenzothiazoline-6-sulfonic acid] radicals (ABTS), superoxide anions (O2) (GW100)
(ii) Significant inhibition of tumor necrosis factor-a (TNF-a), scavenging ABTS and O2
[141]

Butea monospermaFlowerSW480200, 370 μg/mLFloraln-ButanolSignificant antiproliferative effect(i) Significantly downregulated the expression of Wnt signaling proteins such as β-catenin, APC, GSK-3β, cyclin D1, and c-Myc
(ii) Increased intracellular level of ROS
[142]

Rehmannia glutinosaNMCT265, 20, 80 μMNMCatalpolInhibited proliferation and growth invasion of colon cancer cells(i) Downregulated MMP-2 and MMP-9 protein expressions
(ii) Reduction in the angiogenic markers secretions
[143]

Telectadium dongnaienseBarkHCT1161.5, 2.0 μg/mLMeOH extract4-Dicaffeoylquinic acid, quercetin 3-rutinoside, periplocinNM(i) Inhibition of β-catenin/TCF transcriptional activity and effects on Wnt/β-catenin
(ii) Downregulation of the expression of Wnt target genes
[144]

Gloriosa superbaRootSW62030 ng/mLProtein hydrolysate extractProtein hydrolysateNM(i) Upregulation of p53
(ii) Downregulation of NFκB
[145]

Boswellia serrataResinHT-29100, 150 μgMethanolicBoswellic acidDecreased cell viability(i) Reduction in mPGES-1, VEGF, CXCR4, MMP-2, MMP-9, HIF-1, PGE2 expression
(ii) Increment in the caspase 3 activity
(iii) Inhibition of cell migration and vascular sprout formation
[146]

Typhonium flagelliformeLeafWiDr70 μg/mLEthyl acetateGlycoside flavonoid, isovitexin, alkaloidsNMInhibition of COX-2 expression[28]

Diospyros kakiFruitHT-292,000 μg/mLHydroacetone extractPolyphenolImpaired cell proliferation and invasionNM[147]

Carpobrotus edulisLeafHCT1161,000 mg/mLHydroethanolicGallic acid, quercetin, sinapic acid, ferulic acid, luteolin 7-o-glucoside, hyperoside, isoquercitrin, ellagic acid, isorhamnetin 3-O-rutinosideInhibited proliferation(i) Possession of high DPPH scavenging activity and effective capacity for iron binding
(ii) Inhibition of NO radical, linoleic acid peroxidation, protein glycation, and oxidative damage
[148]

Piper methysticumRootHT-2910, 20, 30, 40, 50 μg/mLAqueous11-Hydroxy-12-methoxydihydrokavain, 11-hydroxy-12-methoxydihydrokavain, prenyl caffeate, pinostrobin chalcone, 11-methoxytetrahydroyangonin, awaine, methysticin, dihydromethysticin, 5,6,7,8-tetrahydroyangonin, kavain, 7,8-dihydrokavain, yangonin, desmethoxyyangonin, flavokawain BInhibited the growthNM[26]

Salvia ballotifloraGround aerial partsCT266.76 μg/mLHexane-washed chloroform extract19-Deoxyicetexone, 7,20-dihydroanastomosine, icetexone, 19-deoxyisoicetexoneCytotoxic activityNM[149]

Tinospora cordifoliaStemHCT1161, 10, 30, 50 μMHydroalcoholicClerodane furano diterpene glycoside, cordifoliosides A and Β, sitosterol, ecdysterone, 2β,3β:15,16-diepoxy-4α, 6β-dihydroxy-13(16),14-clerodadiene-17,12:18,1-diolideInduced chromatin condensation and fragmentation of nuclei of few cells(i) Considerable loss of MMP
(ii) Decreased in mitochondria function
(iii) Increased cytochrome c in the cytosol
(iv) Induced ROS/oxidative stress
(v) Increased autophagy
[150]

Euterpe oleraceaFruitNM35 μg/mLHydroethanolicVanillic acid, orientin, isoorientinNM(i) Scavenging capacity towards ROO and HOCl
(ii) Inhibition of nitroso compound formation
[151]

Salvia miltiorrhizaNMHCT116, EthanolicDiterpene quinoneNMDecreased levels of pro-caspases 3 and 9[152]

CoffeaBeanHCT1161 mg/mLAqueousChlorogenic acid complex (CGA7)NM(i) DNA fragmentation, PARP-1 cleavage, caspase 9 activation, downregulation of Bcl-2 and upregulation of Bax[153]

Illicium verumFruitHCT11610 mg/mLEthanolicGallic acid quercetinInduction of apoptosis and inhibition of key steps of metastasisNM[154]

Garcinia propinqua CraibLeafHCT116NMCH2Cl2 extractBenzophenones, xanthones, and caged xanthonesPotent inhibitory cytotoxicitiesNM[155]
Stem, barkHCT11614.23, 23.95 μMMeOH, CH2Cl2, and EtOAc extractXerophenone A, doitunggarcinones A and B, sampsonione, 7β-H-11-benzoyl-5α-ydroxy-6, 10-tetramethyl-1-(3-methyl-2-butenyl)-tetracyclotetradecane-2,12,14-trione, hypersampsone M, assiguxanthone A (cudraxanthone Q), 40 10-O-methylmacluraxanthone (16), 41- and 5-O-methylxanthone V1NMNM[156]

Malus pumila Miller cv. AnnurcaFruitCaco-2400 mg/LMethanolicChlorogenic acid, (+)catechin, (–)epicatechin, isoquercetin, rutin, phloridzin, procyanidin B2, phloretin, quercetinWNT inhibitors and reduced WNT activity elicited by WNT5ANM[157]

Malus domestica cv. LimoncellaFruitCaco-2400 mg/LMethanolicChlorogenic acid, (+)catechin, (–)epicatechin, isoquercetin, rutin, phloridzin, procyanidin B2, phloretin, quercetinWNT inhibitors and reduced WNT activity elicited by WNT5ANM[157]

Coix lacryma-jobi var. ma-yuenLeafHCT1160.5, 1 mg/mLAqueousCoixspirolactam A, coixspirolactam B, coixspirolactam C, coixlactam, methyl dioxindole-3-acetateNMInhibited migration, invasion, and adhesion via repression of the ERK1/2 and Akt pathways under hypoxic conditions[158]

Mesua ferreaStem, barkHCT116, HT-293.3, 6.6, and 11.8 μg/mLNMFractions (α-amyrin, SF-3, n-Hex)Downregulation of multiple tumor promoterUpregulation of p53, Myc/Max, and TGF-β signaling pathways[159]

TaraxacumRootSGC7901, BGC8233 mg/mLAqueousNMNMProliferation and migration through targeting lncRNA-CCAT1[160]

Portulaca oleraceaLeafHT-29 CSCs2.25 μg/mLAlcoholicOxalic, malic acidNMInhibited expression of the Notch1 and β-catenin genes, regulatory and target genes that mediate the Notch signal transduction pathway[161]

Hordeum vulgare L.NMHT-29NMAqueous & juiceProtein, dietary fiber, the B vitamins, niacin, vitamin B6, manganese, phosphorus, carbohydrates(i) Inhibited proliferation of cancer cells
(ii) Cytotoxic activity
Free radical scavenging activity[162]

Paraconiothyrium sp.NMCOLO 205 and KM1212.5 μMMethyl ethyl ketone extractn-Hexane, CH2Cl2, EtOAc, and MeOH fractions (A−D)(i) Growth inhibitory activity
(ii) Antiproliferative effect
NM[163]

Mentha×piperitaLeafHCT1165, 10, 20, 30, 40, 50 μg/mLAqueousPolyphenolsNMInhibited replication of DNA and transcription of RNA which induce the ROS[164]

Mammea longifolia Planch. and TrianaFruitSW48025, 50, 100 μg/mLMethanolicNMNMMitochondria-related apoptosis and activation of p53[165]

Rollinia mucosa (Jacq.) Baill.NMHCT116, SW-480<4, <20 μg/mLEtOHRollitacin, jimenezin, membranacin, desacetyluvaricin, laherradurinCytotoxic activityNM[54]

Annona diversifolia Saff.NMSW-4800.5 μg/mLNMCherimolin-2Cytotoxic activityNM[54]

A. purpurea Moc. & Sessé ex DunalNMHT-291.47 μg/mLCHCl3-MeOHPurpurediolin, purpurenin, annoglaucin, annonacin ACytotoxic activityNM[54]

Viguiera decurrens (A.Gray) A. GrayNMNM3.6 μg/mLHex; EtOAc; MeOHβ-Sitosterol-3-O-β-D-glucopyranoside; β-D-glucopyranosyl oleanolate; β-sitosterol-3-O-β-D-glucopyranoside, and oleanolic acid-3-O-methyl-β-D-glucuronopyranoside ronoateCytotoxic activityNM[54]

Helianthella quinquenervis (Hook.) A. GrayNMHT-292-10 μg/mLNMDemethylencecalinCytotoxic activityNM[54]

Smallanthus maculatus (Cav.) H. Rob.NMHCT15<20 μg/mLAcetoneFraction F-4, fraction F-5, ursolic acidCytotoxic activityNM[54]

Bursera fagaroides (Kunth) Engl.NMHF61.8×10-4 to 2.80 μg/mLHydroalcoholicPodophyllotoxin, β-peltatin-A methyl ether, 5-desmethoxy-β-peltatin-A methyl ether, desmethoxy-yatein, deoxypodophyllotoxin, burseranin, acetyl podophyllotoxinNM(i) Inhibitor of microtubules
(ii) Ability to arrest cell cycle in metaphase
[54]

Viburnum jucundum C.V. MortonNMHCT15<20 μg/mLAcetoneUrsolic acidCytotoxic activityNM[54]

Hemiangium excelsum (Kunth) A.C.Sm.NMHCT15<10 (μg/mL)MeOHPE, EtOAc, MeOHCytotoxic activityNM[54]

Hyptis pectinata (L.) Poit.NMCol2<4, <20 μg/mLNMPectinolide A, pectinolide B, pectinolide C, α-pyrone, boronolide, deacetylepiol-guineCytotoxic activityNM[54]

H. verticillata Jacq.NMCol2<4,<20 μg/mLNMDehydro-β-peltatin, methyl ether dibenzylbutyrolactone, (-)-yatein, 4-demethyl-deoxypodophyllotoxinNonspecific cytotoxic activityNM[54]

H. suaveolens (L.)NMHF62.8-12 μg/mLChloroform and butanolβ-ApopicropodophyllinNonspecific cytotoxic activityNM[54]

Salvia leucantha Cav.Leaf, root, stemHF6, HT-29, HCT1514.9, 12.7, 9.9 μg/mLCHCl3NMCytotoxic activityNM[54]

Vitex trifolia L.NMHCT153.5 to <1 (μg/mL)Hexane and dichloromethaneSalvileucalin B, Hex: leaf, Hex: stem, DCM: leaf, DCM: stemCytotoxic activityNM[54]

Persea americana Mill.NMHT-29<4 μg/mL and <20 μg/mLEthanolic1,2,4-trihydroxynonadecan, 1,2,4-trihydroxyheptadec-16-ene, 1,2,4-trihydroxyheptadec-16-yneCytotoxic activityNM[54]

Linum scabrellumRoots, aerial partsHF60.2, 0.5, 2.3 μg/mLChloroform and butanolDCM: MeOH, 6MPTOXPTOXNM(i) Induction of cell cycle arrest in G2/M
(ii) Inhibition of tubulin polymerization
[54]

Phoradendron reichenbachianum (Seem.) Oliv.NMHCT153.6, 3.9, and 4.3 μg/mLNMMoronic acidCytotoxic activityNM[54]

Cuphea aequipetala Cav.NMHCT1518.70 μg/mLAcetoneNMCytotoxic inactivityNM[54]

Galphimia glauca Cav.NMHCT150.63, 0.50, 1.99 μg/mLEtOH, MeOH, aqueousNMCytotoxic activityNM[54]

Mimulus glabratus KunthNMHF612.64 μg/mLMeOHNMCytotoxic activityNM[54]

Picramnia antidesma Sw.NMHCT150.6 to 4.5 μMNM10-Epi-uveoside, uveoside, picramnioside E, picramnioside DCytotoxic activityNM[54]

Penstemon barbatus (Cav.) RothNMHF615.19 μg/mLMeOHNMCytotoxic activityNM[54]

P. campanulatus (Cav.) Willd.NMHF66.74 μg/mLMeOHNMCytotoxic activityNM[54]

Veronica americana Schwein. ex Benth.NMHF60.169 and 1.46 μg/mLMeOHNMCytotoxic activityNM[54]

Zea mays L.NMHCT116, SW-480, SW-620NMNM13-Hydroxy-10-oxo-trans-11-octadecenoic acidCytotoxic activityNM[54]

Colubrina macrocarpa (Cav.) G. DonNMHCT1510, 2.1, 9.1 μg/mLPE, EtOAc, MeOHNMCytotoxic activityNM[54]

Coix lacryma-jobiSeed, endosperm, and hullHT-290.1–1,000 μg/mLMethanolic, hexanePhytosterols (campesterol, stigmasterol, and β-sitosterol), gamma-linolenic acid (GLA), arachidonic acid (AA), eicosapentaenoicacid (EPA) and docosahexaenoic acid (DHA), linoleic acidNM(i) Influence of signal transduction pathways that involve the membrane phospholipids
(ii) Enhancement of ROS generation and decrease of cell antioxidant capacity
[166]

Abutilon indicumLeafHT-29210 μg/mLAqueousFlavonoids (4H-pyran-4-one, 2,3-dihydro-3,5-dihydroxy-6-methyl, 2-ethoxy-4-vinylphenol, N,N-dimethylglycine, lup-20(29)-en-3-one, linolenin, 1-mono-, 9-hexadecanoic acid methyl ester, linolenic acid methyl ester), phenolic (amino acids, terpenoids, fatty acids, methyl palmitoleate)NM(i) Increase in the levels of reactive oxygen species and simultaneous reduction in cellular antioxidant, mitochondrial membrane loss, DNA damage, and G1/S phase cell cycle arrest[167]

Galla rhoisNMHCT116, HT-2912.5, 25, 50, 100, 200 μg/mLAqueous with steaming processGallotanninsIncreased contents of gallic acid and ellagic acid(i) Induced apoptosis through the activation of caspases 3, 8, 9
(ii) Modulated activation of mitogen and protein kinases, p38, and c-Jun NH2-terminal kinase
[168]

Artemisia annua LinnéPowderHCT11620, 30, 40, 60, 80, 100 μg/mLEthanolicPhenolic compoundsInhibited cell viability and increased LDH release(i) PTEN/p53/PDK1/Akt signal pathways through PTEN/p53 induce apoptosis
(ii) Increased apoptotic bodies, caspase 3 and 7 activation
(iii) Regulated cytochrome c translocation to the cytoplasm and Bax translocation to the mitochondrial membrane
[169]

Nelumbo nucifera stamenPowderHCT116100, 200, 400 μg/mLEthanolic crudeNMNM(i) Increased the sub-G1 population, mRNA levels of caspases 3 and 8, levels of IκBα and caspase 9
(ii) Modulated the Bcl-2 family mRNA expression
(iii) Reduced the mRNA levels of NFκB
[170]

Corn silkNMLoVo, HCT1161.25, 2.5, 5, 10, 20 μg/mLAqueousProteins, polysaccharides, flavonoid, vitamins, tannins, alkaloids, mineral salts, steroidsNM(i) Increase in the Bax, cytochrome c, caspases 3 and 9 levels[171]

Lycium barbarum L.PowderHT-291, 2, 3, 4, 5 μg/mLNMNeoxanthin, all-trans-β-cryptoxanthin, polysaccharides, carotenoids, flavonoidsNM(i) Upregulation of p53 and p21 expression
(ii) Downregulation of the CDK2, CDK1, cyclin A, and cyclin B expression
(iii) Arrest in the G2/M phase of cell cycle
[172]

Chrysobalanus icaco L.Freeze-dried fruitHT-291, 2.5, 5, 10, 20 μg/mLCrude ethyl acetateDelphinidin, cyanidin, petunidin, and peonidinNM(i) Increased intracellular ROS production
(ii) Decreased TNF-α, IL-1β, IL-6, and NFκB1 expressions
[173]

Zanthoxylum piperitum De CandolleFruitCaco-2, DLD-1200 μg/mLAqueousNMNM(i) Increased the phosphorylation of c-Jun N-terminal kinase (JNK)[174]

Celtis aetnensis (Tornab.) Strobl (Ulmaceae)TwigsCaco-25, 50, 100, 250, or 500 μg/mLMethanolicFlavonoid and triterpenic compoundsNM(i) Increase in the levels of ROS
(ii) Decrease in RSH levels and expression of HO-1
[175]

Rosa caninaPeel and pulpCaco-262.5, 125, 250, 500 μg/mLTotal extract (fraction 1), vitamin C (fraction 2), neutral polyphenols (fraction 3), and acidic polyphenols (fraction 4)PolyphenolsDecreased production of reactive oxygen species (ROS)NM[176]

Rhazya strictaLeafHCT11647, 63, 79, and 95 μg/cm2Crude alkaloidAlkaloidsNM(i) Downregulated DNA-binding and transcriptional activities of NFκB and AP-1 proteins
(ii) Increase in Bax, caspases 3/7 and 9, p53, p21 and Nrf-2 levels
(iii) Decrease in expression of ERK MAPK, Bcl-2, cyclin D1, CDK-4, survivin, and VEGF
[177]

Green coffeeNMCaco-210-1,000 μg/mLNM5-Caffeoylquinic acid (5-CQA), 3,5-dicaffeoylquinic acid (3,5-DCQA), ferulic acid (FA), caffeic acid (CA), dihydrocaffeic acid (DHCA), dihydroferulic acid (DHFA)Reduced viability of cancer cellsNM[178]

Flourensia microphyllaLeafHT-29NMEthanolic and acetonePhenolic compoundsNM(i) Inhibition of IL-8
(ii) Activation of apoptosis by the increment of the Bax/Bcl-2 ratio and expression of TNF family
[179]

NM: not mentioned.
3.1.2. Studies in Animal Models

The most used animal model is the murine one (Tables 2(a) and 2(b)). In particular, studies were carried out above all on HT-29 and HCT116 cells. The effects of the different medicinal plants and their extracts are essentially the same detected in in vitro studies. In particular, plant extracts were able to induce apoptosis and inhibit proliferation and tumor angiogenesis by regulating p53 levels and checkpoint proteins with consequent cell cycle arrest and antiproliferative and antiapoptotic effects on cancerous cells.

(a) Efficacy of medicinal plants on colon cancer in in vivo models

Scientific nameParts usedModelDoseType of extractImportant compoundsCellular effectMechanismsReferences

Vitis viniferaSeedIn vivo (murine)Caco-2In vivo: 400–1,000 mg/kg
In vitro: 10–25 μg/mL
AqueousProcyanidins(i) Increased crypt depth and growth-inhibitory effects
(ii) Inhibited cell viability
(iii) Significantly decreased the histological damage score
Reduced MPO (myeloperoxidase) activity[180]
SeedIn vivoHT-29, SW4805 mg/kgAqueousNMNMDecreased VEGF, TNF, MMP-1, MMP-3, MMP-7, MMP-8, MMP-9, and MMP-13 protein expression[181]
SkinIn vivoNM7.5, 30, 60 μg/mLMethanolic4-Geranyloxyferulic acidNMNM[30]
SeedIn vivo (murine)NM0.12% NMCatechin, epicatechinNM(i) Suppressed proliferation, sphere formation, nuclear translocation of β-catenin and Wnt/β-catenin signaling
(ii) Elevated p53, Bax/Bcl-2 ratio, and cleaved PARP and mitochondrial-mediated apoptosis
[31]

Camellia sinensisLeafIn vivo (murine)HT-29In vitro: 0, 10, 30, 50 μM
In vivo: 1.5 mg per day
AqueousCatechin, epigallocatechin gallate1.9-fold increase in tumor endothelial cell apoptosisInhibited the ERK-1 and ERK-2 activation, VEGF expression, and VEGF promoter[182]
In vivo (murine)HCT1160.5%NMNMReduced basement membraneInhibition of MMP-9 and VEGF secretion[183]
In vivo (murine)Caco-2, HT-29300 μMAqueousTheaflavins (TF-2, TF-3, TF-1)Induced apoptosis of human colon cancer cellsInhibition of edema formation correlated to attenuation of COX-2 expression and promoter analysis revealed modulation of NFκB, AP-1, CREB, and/or NF-Il-6 (C/EBP)[36]
In vivo (murine)HT11525 μg/mLHydroethanolicPhenolic compounds (p-hydroxyphenyl ethanol, pinoresinol & dihydroxyphenyl ethanol)NMInhibition via reduced expression of a range of α5 & β1[184]

Sasa quelpaertensisLeafIn vivoHT-29, HCT1160, 100, 200, 300 mg/LEthanolicp-Coumaric acid, tricinInhibition of colony formation(i) Nonadherent sphere formation suppressed CD133+ & CD44+ population
(ii) Downregulated expression of cancer stem cell markers
[41]

AnoectochilusNMIn vivoCT26Oral dose of 50 & 10 mg/mouse per dayAqueousKinsenosideStimulated proliferation of lymphoid tissuesActivation of phagocytosis of peritoneal macrophages[185]

Purple-fleshed potatoesFruitIn vivoColon cancer stem cells5.0 μg/mLEthanol, methanol, ethyl acetateAnthocyanin, β-catenin, cytochrome cReduction in colon CSCs number and tumor incidence(i) Increase in cytochrome c levels from p53 status and maybe mitochondria-mediated apoptosis
(ii) Suppressed levels of cytoplasmic and nuclear β-catenin
[58]

Phaseolus vulgarisLeafIn vivoHT-29NmEthanolicPolysaccharides, oligosaccharidesInduction of apoptosis and inhibit proliferation(i) Inactivation of the retinoblastoma phosphoprotein
(ii) Induced G1 arrest
(iii) Suppression of NF-jb1
(iv) Increase in EGR1 expression
[59]

Rosmarinus officinalis L.LeafIn vivoHT-29SC-RE 30 μg/mL and CA 12.5 μg/mLEthanolicPolyphenols (carnosic acid (CA) and carnosol)(i) Activation of Nrf2 transcription factor
(ii) Activated common regulators, such as XBP1 (Xbp1) gene, SREBF1/SREBF2 (Srebp1/2), CEBPA and NR1I2 (Pxr) genes
LeafIn vivo (rat)NMNMEthanolicRosmanol and its isomers, carnosol, rosmadial, carnosic acid, and 12-methoxycarnosic acid, carnosic acid, carnosolInteractions with the gut microbiota and by a direct effect on colonocytes with respect to the onset of cancer or its progressionNM

Wasabia japonicaRhizomesIn vivoCOLO 2055 mg/mLMethanolic6-(Methylsulfinyl)hexyl isothiocyanateAnticolon cancer properties through the induction of apoptosis and autophagy(i) Activation of TNF-α, Fas-L, caspases
(ii) Truncated Bid and cytochrome c
(iii) Decreased phosphorylation of Akt and Mtor
(iv) Promoted expression of microtubule-associated protein 1 light chain 3-II and AVO formation
[186]

ZingiberaceaeRhizomeHT-29HT-295 g/kgDichloromethanicTurmeroneSuppressed the proliferation of HT-29 colon cancer cells(i) LDH release
(ii) ROS generation
(iii) Collapse in mitochondrial membrane potential
(iv) Cytochrome c leakage
(v) Activation of caspase 9 and caspase 3
[187]

Panax quinquefoliusRootIn vivo (murine)NM30 mg/kgEthanolicGinsenosides (protopanaxadiol or protopanaxatriol)Attenuated azoxymethane/DSS-induced colon carcinogenesis by reducing the colon tumor number and tumor load(i) Reduced experimental colitis
(ii) Attenuated on AOM/DSS-induced colon carcinogenesis
(iii) Proinflammatory cytokines activation
(iv) Suppressed DSS
(v) Downregulated inflammatory cytokine gene expression
[188]

MyrtaceaeLeafIn vivo (murine)HCT116100 μg/mL (in vitro) 200 and 100 μg/disc (in vivo)MethanolicPhenolics, flavonoids, betulinic acidInhibition of tumor angiogenesis(i) Inhibition of angiogenesis of tube formation on Matrigel matrix and HUVECS migration (in vitro)
(ii) Decreased nutrient and oxygen supply and consequently tumor growth and tumor size (in vivo)
(iii) Increased extent of tumor necrosis
[82]

Spica prunellaeLeafIn vivoHT-29200 mg/mL (in vitro), 600 mg/mL (in vivo)EthanolicRosmarinic acidInduction of apoptosis and inhibition of cell proliferation and tumor angiogenesis(i) Induced apoptosis
(ii) Inhibited cancer cell proliferation and angiogenesis STAT3 phosphorylation
(iii) Regulated expression of Bcl-2, Bax, cyclin D1, CDK4, VEGF-A, and VEGFR-2 (in vivo)
[83]

Gymnaster koraiensisAerial partIn vivo (murine)NM500 μmol/kgEthanolicGymnasterkoreaynes B, C, E, 2,9,16-heptadecatrien-4,6-dyne-8-olAnti-inflammatory and cancer preventive activities(i) Significant decrease in expression of COX-2
(ii) Increase in serum IL-6
[189]

Allium fistulosumEdible portionsIn vivo (murine)CT2650 mg/kg b.w.Hot waterp-Coumaric acid, ferulic acid, sinapic acid, quercitrin, isoquercitrin, quercetol, kaempferolSuppression of tumor growth and enhanced survival rate of test mice(i) Decreased expression of inflammatory molecular markers
(ii) Downregulated expression of MMP-9 and ICAM
(iii) Metabolite profiling and candidate active phytochemical components
[190]

Annona squamosa LinnLeafIn vivo (animal)HCT1168.98 μg/mLCrude ethyl acetateAcetogenins (annoreticuin & isoannoreticuin) and alkaloids dopamine, salsolinol, and coclaurine(i) Inhibited growth and proliferation of tumor cellsReactive oxygen species (ROS) formation, lactate dehydrogenase (LDH) release, and caspases 3/7, 8, 9 activation[191]

Eupatorium cannabinumAerial partsIn vivo (murine)HT-2925 μg/mLEthanolicPyrrolizidine alkaloids (senecionine, senkirkine, monocrotaline, echimidine)Cytotoxicity against colon cancer cells(i) Upregulation of p21 and downregulation of NCL, FOS, and AURKA, indicating reduced proliferation capacity
(ii) Mitotic disruption and nonapoptotic cell death via upregulation of Bcl-xL
[96]

Flacourtia indicaAerial partsIn vivo (murine)HCT116500 μg/mLMethanolicPhenolic glucoside (flacourticin, 4-benzoylpoliothrysoside)Antiproliferative and proapoptotic effects in HCT116 cellsApoptosis via generation of ROS and activation of caspases (PARP)[192]

Sorghum bicolorThe dermal layer of stalkIn vivo (murine)HCT116 & colon cancer stem cells>16 and 103 μg/mLPhenolic, acetoneApigeninidin & luteolinidinAntiproliferative effect(i) Target p53-dependent and p53-independent pathways[97]

Gleditsia sinensisThornIn vivo (murine)HCT116800 μg/mLAqueousFlavonoid, lupine acid, ellagic acid glycosidesInhibited proliferation of colon cancer(i) Increased p53 levels
(ii) Downregulation of the checkpoint proteins, cyclin B1, Cdc2, and Cdc25c
[90]
ThornIn vivo (murine)HCT116600 μg/mLEthanolicNMInhibitory effect on the proliferation of human colon cancer HCT116 cells(i) Caused G2/M phase cell cycle arrest[91]

Zingiber officinaleRhizomeIn vitro/in vivo (murine)HCT1165 μMEthanolic6-Paradol, 6- and 10-dehydrogingerdione, 6- and 10-gingerdione, 4-, 6-, 8-, and 10-gingerdiol, 6-methylgingerdiol, zingerone, 6-hydroxyshogaol, 6-, 8-, 10-dehydroshogaol, diarylheptanoidsInhibitory effects on the proliferation of human colon cancer cells(i) Arrest of G0/G1 phase
(ii) Reduced DNA synthesis
(iii) Induced apoptosis
[103]

Cucumaria frondosaThe enzymatically hydrolyzed epithelium of the edibleIn vivo (murine)HCT116<150 μg/mLHydroalcoholicMonosulphated triterpenoid glycoside frondoside A, the disulphated glycoside frondoside B, the trisulphated glycoside frondoside C(i) Inhibition at S and G2-M phase with a decrease in Cdc25c
(ii) Increase in p21WAF1/CIP
(i) Inhibition the growth of human colon
(ii) Apoptosis associated with H2AX phosphorylation and caspase 2
[105]

Rolandra fruticosaLeaf & twigsIn vivo (murine)HT-2910 and 5 mg/kg/dayMethanolicSesquiterpene lactone (13-acetoxyrolandrolide)Antiproliferative effect against human colon cancer cells(i) Inhibition of the NFκB pathway, subunit p65 (RelA) and upstream mediators IKKβ and oncogenic K-ras[106]

Cydonia oblonga MillerLeaf & fruitIn vivo (murine)Caco-2250–500 μg/mLMethanolicPhenolic compound (flavonol and flavone heterosides, 5-O-caffeoylquinic acid)Antiproliferative effect against human kidney and colon cancer cells(i) Suppression of NFκB activation, activator (AP-1), mitogen-activated protein kinases, namely, PKC, (GFR)-mediated pathways
(ii) Cell cycle arrest
(iii) Induction of apoptosis, antioxidant, and anti-inflammatory effects
[107]

Sedum kamtschaticumAerial partIn vivo (murine)HT-290–0.5 mg/mLMethanolicBuddlejasaponin IVInduced apoptosis in HT-29 human colon cancer cells(i) Induced apoptosis via mitochondrial-dependent pathway triggered by downregulation of Bcl-2 protein levels, caspase 3 activation, and subsequent PARP cleavage[109]

Ganoderma lucidumCaps & stalksIn vivo (murine)HT-290-0.1 mg/mLTriterpene extract (hot water) extractPolysaccharides (mainly glucans & glycoproteins), triterpenes (ganoderic acids, ganoderic alcohols, and their derivatives)Cytokine expression inhibited during early inflammation in colorectal carcinomaInduced autophagy through inhibition of p38 mitogen-activated kinase and activation of farnesyl protein transferase (FPT)[193]

Ginkgo bilobaFruit & leafIn vivo (murine)HT-2920–320 mg/LAqueousTerpene lactones and flavonoid glycosidesInhibited progression of human colon cancer cells induced HT-29 cell apoptosis(i) Activation in caspase 3, reduction in Bcl-2 expression, and elevation in p53 expression[112]

Rubus occidentalisFruitIn vivo (murine)JB6 Cl 4125 μg/mLMethanolicβ-Carotene, α-carotene, ellagic acid, ferulic acid, coumaric acidInhibited tumor development(i) Impaired signal transduction pathways leading to activation of AP-1 and NFB RU-ME fraction[194]

Oryza sativaSeedIn vivo (murine)HT-29, SW 480, HCEC100 μg/mLEthyl acetate extractPhenolic compound (tricin, ferulic acid, caffeic acid, and methoxycinnamic acid)Inhibited growth of human colon cancer cells(i) Induction of apoptosis by enhanced activation of caspases 8 and 3
(ii) Decreased the number of viable SW480 and HCEC cells
[113]

Cistanche deserticolaDried stemIn vivo (murine)SW480In vivo: 0.4 g/kg/day
In vitro: 100 mg/mL
AqueousPolysaccharides, phenylethanoid glycosidesDecreased mucosal hyperplasia and helicobacter infection(i) Increased number of splenic macrophages and NK cells
(ii) Decreased frequency of hyperplasia and H. hepaticus infection of the intestine
[133]

Rehmannia glutinosaNMIn vivo (male C57BL6 mice and Sprague-Dawley rats)CT2628 mg/kgNMCatalpol(i) Inhibited proliferation, growth, and expression of angiogenic markers(i) VEGF, VEGFR2, HIF-1α, bFGF inhibited the expressions of inflammatory factors such as IL-1β, IL-6, and IL-8[143]

Olea europaeaOlive mill wastewaterIn vivo (murine)NMNMMethanolicHydroxytyrosolInterferes with tumor cell growthNM[195]
LeafIn vivo (xenograft model) (murine)HCT116, HCT80, 5, 10, 20, 30, 50, and 70 μg/mLPhenolicOleuropein and hydroxytyrosolNM(i) Activation of caspases 3, 7, and 9
(ii) Decrease of mitochondrial membrane potential and cytochrome c release
(iii) Increase in intracellular Ca2+ concentration
[196]

Ginkgo biloba L.LeafIn vivo (rat)NM0.675 and 1.35 g/kgMethanolicFlavonoid glycosides, terpene lactones, and ginkgolic acids(i) Suppressed tumor cell proliferation, promoted apoptosis, and mitigated inflammationNM[197]

Rhus trilobata Nutt.NMIn vivo (hamster)NM400 mg/kg, 100 mg/kgAqueousTannic acid, gallic acidCytotoxic activityNM[54]

Annona diversifolia Saff.NMIn vivo (mice)SW-4801.5, 7.5 mg/kg/dayNMLaherradurinCytotoxic activityNM[54]

A. muricata L.NMIn vivo (rat)NM250/500 mg/kgEtOAcA, B, and C, and cis- and trans-annomuricin-D-onesCytotoxic activityNM[54]

Plumeria acutifolia Poir.NMIn vivo (hamster)NM400 mg/kg/dayAqueousNMCytotoxic activityNM[54]

Lasianthaea podocephala (A. Gray) K. M. BeckerNMIn vivo (hamster)NM200 mg/kg/dayAqueousNMCytotoxic activityNM[54]

Flourensia cernua DC.NMIn vivo (hamster)NM350 mg/kg/dayAqueousFlavonoids, sesquiterpenoids, monoterpenoids, acetylenes, p-acetophenones, benzopyrans, benzofuransCytotoxic activityNM[54]

Ambrosia ambrosioides (Cav.) W. W. PayneNMIn vivo (hamster)NM400 mg/kg/dayAqueousNMCytotoxic activityNM[54]

Alnus jorullensis KunthNMIn vivo (hamster)NM175 mg/kg/dayAqueousNMCytotoxic activityNM[54]

Dimorphocarpa wislizeni (Engelm.) RollinsNMIn vivo (hamster)NM100 mg/kg/dayAqueousNMCytotoxic activityNM[54]

Euphorbia pulcherrima Willd. ex KlotzschNMIn vivo (hamster)NM200 mg/kg/dayAqueousNMCytotoxic activityNM[54]

Acalypha monostachya Cav.NMIn vivo (hamster)NM400 mg/kg/dayAqueousNMCytotoxic activityNM[54]

Crotalaria longirostrata Hook. & Arn.NMIn vivo (hamster)NM400 mg/kg/day, 350 mg/kg/dayEtOH-CHCl3NMCytotoxic activityNM[54]

Asterohyptis stellulata (Benth.) EplingNMIn vivo (hamster)NM50 mg/kg/dayAqueousNMCytotoxic activityNM[54]

Acacia constricta A. GrayNMIn vivo (hamster)NM400 mg/kg/dayAqueousNMCytotoxic activityNM[54]

Holodiscus dumosus A. HellerNMIn vivo (hamster)NM350 mg/kg/dayAqueousNMCytotoxic activityNM[54]

Butea monospermaFlowerIn vivo (rat)HT-29150 mg/kgn-Butanol extractIsocoreopsin, butrin, and isobutrinFree radical scavenging and anticancer activitiesNM[198]

Taraxacum spp.RootIn vivo (xenograft murine model)HT-29, HCT11640 mg/kg/dayAqueousα-Amyrin, β-amyrin, lupeol, and taraxasterolInduced programmed cell deathNM[199]

NM: not mentioned.
(b) Other effects of medicinal plants in in vivo models

Scientific nameParts usedModelDoseType of extractImportant compoundsCellular effectMechanismsReferences

Allium sativumRootIn vivo (murine)NM2.4 mL of dailyEthanolicAllicin, S-allylmercaptocysteineSignificantly suppressed both the size and number of colon adenomasEnhancement of detoxifying enzymes: SAC and GST activity[200]

Olea europaeaFruitIn vivoCaco-250 μMAqueousPhenolic compounds, authentic hydroxyl tyrosol (HT)(i) Effect of OPE and HT on CB1 associated with reduced proliferation of Caco-2 cells
(ii) Increase in CB1 expression in the colon of rats receiving dietary EVOO
Increase in Cnr1 gene expression, CB1 protein levels[201]
In vivo (murine)HT11525 μg/mLHydroethanolicPhenolic compounds (p-hydroxyphenyl ethanol, pinoresinol & dihydroxyphenyl ethanol)NMInhibition via reduced expression of a range of α5 & β1[184]

Origanum vulgare L.LeafIn vivo (murine)NM20, 40, 60 mg·kg−1AqueousRosmarinic acid, caffeic acid, flavonoidsAntioxidant status(i) Increased LPO products and activity of SOD and CAT enzymes and GST and GPx activity
(ii) Antioxidant and anticarcinogenic effect
[202]

HazelnutSkinIn vivoNMThe flow rate 0.21 mL/min and injection volume 9.4 μLAqueousFlavan-3-ols, in monomeric and polymeric forms, and phenolic acids(i) Decreased circulating levels of free fatty acids and triglycerides
(ii) Higher excretion of bile acid
Increase of the total antioxidant capacity of plasma[203]

Apples and apple juiceFruitIn vivoNM90 mg/LAqueousPhenolic acids, flavonoids, tannins, stilbenes, curcuminoidsNMNM[204]

Grifola frondosaFruitIn vivo (murine)HT-2910 ng/mLAqueousPhenolic compounds (pyrogallol, caffeic acid, myricetin, protocatechuic acid, etc.)Inhibition of TNBS-induced rat colitis(i) Induced cell cycle progression in G0/G1 phase and apoptotic death[104]

Ruta chalepensisLeafIn vivo (human)NM250 μg/mLEthanolicRutin, gallic acid, catechin hydrate, naringinOxidative profile in patients with colon cancerNM[205]

Cannabis sativaDry flower & leafIn vivo (murine)DLD-1 and HCT1160.3–5 μMMethanolicCannabidiol, phytocannabinoidsNM(i) Reduced cell proliferation in a CB1-sensitive and AOM-induced preneoplastic lesions and polyps
(ii) Inhibition of colorectal cancer cell proliferation via CB1and CB2 receptor activation
[121]

Melia toosendanFruitIn vivo (murine)SW480, CT260, 10, 20, 30, 40, 50 μg/mLEthanolicTriterpenoids, flavonoids, polysaccharide, limonoidsNM(i) Inhibited cell proliferation of SW480 and CT26 by promoting apoptosis as indicated by nuclear chromatin condensation and DNA fragmentation
(ii) Induced caspase 9 activity which further activated caspase 3 and poly(ADP-ribose) polymerase cleavage, leading the tumor cells to apoptosis
[123]

Smallanthus sonchifoliusRootIn vivo (murine)NM73.90, 150.74, 147.65, and 123.26 mg/kgAqueousFructansNMReduction incidence of colon tumors expressing altered β-catenin[206]

Punica granatumPeelIn vivo (adult male Wistar rats)NM4.5 g/kgMethanolicGallic acid, protocatechuic acid, cateachin, rutin, ellagic acid, punicalaginNM(i) Reduction in TGF-β, Bcl-2, EGF, CEA, CCSA-4, MMP-7 and in COX-2, cyclin D1, survivin content
(ii) Downregulated expression of β-catenin, K-ras, c-Myc genes
[207]

Linum usitatissimumSeedIn vivo (male Sprague-Dawley rats)NM500 mg/kgAlkalineSecoisolariciresinol diglucoside, carbohydrates, proteins, and tanninsReduced the serum fasting glucose levelsSignificantly reduced the HbA1c, insulin levels, and proinflammatory cytokines[208]

Diospyros kakiFruitIn vivo (male CD-1 mice)NM15 mg/kgHydroacetonePolyphenol(i) Decreased attenuation of colon length in diarrhea severity
(ii) Reduced mortality rate
(iii) Reduction of the extent of visible injury (ulcer formation) and of mucosal hemorrhage
Decreased expression of COX-2 and iNOS in the colonic tissue[147]

Muntingia calaburaLeafIn vivo (rat)NM50, 250, 500 mg/kgMethanolicRutin, gallic acid, ferulic acid, and pinocembrinReduction of the colonic oxidative stress, increasing the antioxidants levels possibly via the synergistic action of several flavonoidsNM[209]

Portulaca oleraceaNMIn vivo (murine)HT-29 CSCs2.25 μg/mLAlcoholicNMRegulatory and target genes that mediate the Notch signal transduction pathwayInhibition of expression of the Notch1 and β-catenin genes[161]

Aloe veraGelIn vivo (murine)NM400 mg/kg/dayGelPolysaccharidesNM(i) Via inhibition of the cell cycle progression
(ii) Induction of cellular factors, such as extracellular signal-regulated kinases 1/2, cyclin-dependent kinase 4, and cyclin D1; on the other hand, PAG increased the expression of caudal-related homeobox transcription factor 2
[210]

Artemisia annua LinnéPowderIn vivo (xenograft murine model)HCT11620, 40 mg/kg/dayEthanolicPhenolic compoundsNM(i) Induced apoptosis via PTEN/p53/PDK1/Akt signal pathways through PTEN/p53
(ii) Inhibited cell viability and increased LDH release and apoptotic bodies, caspase 3 and 7 activation, and reduced mitochondria membrane potential
(iii) Regulated cytochrome c translocation to the cytoplasm and Bax translocation to the mitochondrial membrane
(iv) Regulation of proteins
[169]

Hordeum vulgarePowderIn vivo (xenograft murine model)HT-292 g/kg and 1 g/kgAqueous (fermented)β-Glucan, protein, amino acids, phenolic compoundsNM(i) Promoted tumor apoptosis by upregulating the mRNA expression of Bax and caspase 3 and downregulating the mRNA expression of Bcl-2 and cyclin D1
(ii) Decreased mRNA expression of Bcl-2 and cyclin D1
(iii) Upregulated expressions levels of Bax and caspase 3
[211]

Dendrophthoe pentandraLeafIn vivo (murine)NM125, 250, 500 mg/kgEthanolicQuercetin-3-rhamnoseNM(i) Decreased the levels of IL-22, MPO levels, proliferation of epithelial cells
(ii) Inhibited S phase of the cell cycle
(iii) Upregulated p53 wild-type gene expression
[212]

Aquilaria crassnaStem, barkIn vivo (murine)HCT1162,000 mg/kg/day
100, 200 mg/kg
NMResin and essential oilsNMNM[213]

Berberis integerrimaNMIn vivo (murine)NM50 and 100 mg/kgHydroalcoholicNMNMNM[214]

Salix aegyptiacaBarkIn vivo (murine)NM100 and 400 mg/kgEthanolicCatechin, catechol, and salicinNMDecreased level of EGFR, nuclear β-catenin, and COX-2[215]

The main mechanisms of action of medicinal plants are summarized in Figure 1.

In in vitro studies, it has been found that grapes, which contain substantial amounts of flavonoids and procyanidins, play a role in reducing the proliferation of cancer cells by increasing dihydroceramides and p53 and p21 (cell cycle gate keeper) protein levels. Additionally, grape extracts triggered antioxidant response by activating the transcriptional factor nuclear factor erythroid 2-related factor 2 (Nrf2) [27].

Grape seeds contain polyphenolic and procyanidin compounds, and their reducing effects on the activity of myeloperoxidase have been shown in in vitro and in vivo studies. It has been suggested that grape seeds could inhibit the growth of colon cancer cells by altering the cell cycle, which would lead eventually to exert the caspase-dependent apoptosis [180].

Another plant that attracted researchers’ attention was soybean, which contain saponins. After 72 h of exposure of colon cancer cells to the soy extract, it was found that this extract inhibited the activity and expression of protein kinase C and cyclooxygenase-2 (COX-2) [34]. The density of the cancer cells being exposed to the soy extract significantly decreased. Soybeans can also reduce the number of cancer cells and increase their mortality, which may be due to increased levels of Rab6 protein [216].

Green tea leaves have also attracted the researchers’ attention in these studies. Green tea leaves, with high levels of catechins, increased apoptosis in colon cancer cells and reduced the expression of the vascular endothelial growth factor (VEGF) and its promoter activity in in vitro and in vivo studies. The extract increased apoptosis (programmed cell death) by 1.9 times in tumor cells and 3 times in endothelial cells compared to the control group [182]. In another in vitro study, the results showed that green tea leaves can be effective in the inhibition of matrix metalloproteinase 9 (MMP-9) and in inhibiting the secretion of VEGF [183].

Garlic was another effective plant in this study. Its roots have allicin and organosulfur compounds. In an in vitro study, they inhibited cancer cell growth and induced apoptosis through the inhibition of the phosphoinositide 3-kinase/Akt pathway. They can also increase the expression of phosphatase and tensin homolog (PTEN) and reduce the expression of Akt and p-Akt [32]. Garlic roots contain S-allylcysteine and S-allylmercaptocysteine, which are known to exhibit anticancer properties. The results of a clinical trial on 51 patients, whose illness was diagnosed as colon cancer through colonoscopy, and who ranged in age from 40 to 79 years, suggest that the garlic extract has an inhibitory effect on the size and number of cancer cells. Possible mechanisms suggested for the anticancer effects of the garlic extract are both the increase of detoxifying enzyme soluble adenylyl cyclase (SAC) and an increased activity of glutathione S-transferase (GST). The results suggest that the garlic extract stimulates mouse spleen cells, causes the secretion of cytokines, such as interleukin-2 (IL2), tumor necrosis factor-α (TNF-α), and interferon-γ, and increases the activity of natural killer (NK) cells and phagocytic peritoneal macrophages [200].

The results of in vitro studies on olive fruit showed that it can increase peroxide anions in the mitochondria of HT-29 cancer cells due to the presence of 73.25% of maslinic acid and 25.75% of oleanolic acid. It also increases caspase 3-like activity up to 6 times and induces programmed cell death through the internal pathway [217]. Furthermore, the olive extract induces the production of reactive oxygen species (ROS) and causes a quick release of cytochrome c from mitochondria to cytosol.

The pomegranate fruit contains numerous phytochemicals, such as punicalagins, ellagitannins, ellagic acid, and other flavonoids, including quercetin, kaempferol, and luteolin glycosides. The results of an in vitro study indicate the anticancer activity of this extract through reduction of phosphorylation of the p65 subunit and subsequent inhibition of nuclear factor-κB (NFκB). It also inhibits the activity of TNF receptor induced by Akt, which is needed for the activity of NFκB. The fruit juice can considerably inhibit the expression of TNF-α-inducing proteins (Tipα) in the COX-2 pathway in cancer cells [43]. The effective and important compounds in pomegranate identified in these 104 studies are flavonoids, polyphenol compounds, such as caffeic acid, catechins, saponins, polysaccharides, triterpenoids, alkaloids, glycosides, and phenols, such as quercetin and luteolin, and kaempferol and luteolin glycosides.

In a systematic review of the plants being studied, some mechanisms were mainly common, including the induction of apoptosis by means of an increase of expression and levels of caspase 2, caspase 3, caspase 7, caspase 8, and caspase 9 in cancer cells, increasing the expression of the proapoptotic protein Bax and decreasing the expression of the antiapoptotic proteins.

Many herbal extracts block specific phase of the cell cycle. For instance, the extract prepared from the leaves of Annona muricata inhibits the proliferation of colon cancer cells and induces apoptosis by arresting cells in the G1 phase [53]. They can also prevent the progress of the G1/S phase in cancer cells [74]. In general, the herbal extracts reported here have been able to stop cancer cells at various stages, such as G2/M, G1/S, S phase, G0/G1, and G1 phase, and could prevent their proliferation and growth.

Other important anticancer mechanisms are the increase of both p53 protein levels and transcription of its gene. Even the increase of p21 expression is not without effect [137]. In an in vitro study on the Garcinia mangostana roots, the results were indicative of the inhibitory effect of the extract of this plant on p50 and P65 activation [93]. Moreover, reduction of cyclin D1 levels and increase of p21 levels are among these mechanisms [137], as well as inhibition of NFκB and reduction of the transcription of its genes, which contribute to reduce the number of cancerous cells [127]. Other important anticancer mechanisms are the inhibition of COX-2, as well as the reduction of the protein levels in this pathway [34]. In addition to this, in some cases, the inhibition of MMP-9 can be mentioned as the significant mechanism of some herbal extracts to kill cancer cells [183].

4. Conclusion and Perspectives

The findings of this review indicate that medicinal plants containing various phytochemicals, such as flavonoids, polyphenol compounds, such as caffeic acid, catechins, saponins, polysaccharides, triterpenoids, alkaloids, glycosides, and phenols, such as quercetin and luteolin, and kaempferol and luteolin glycosides, can inhibit tumor cell proliferation and also intduce apoptosis.

Plants and their main compounds affect transcription and cell cycle via different mechanisms. Among these pathways, we can point to induction of superoxide dismutase to eliminate free radicals, reduction of DNA oxidation, induction of apoptosis by inducing a cell cycle arrest in S phase, reduction of PI3K, P-Akt protein, and MMP expression, reduction of antiapoptotic Bcl-2, Bcl-xL proteins, and decrease of proliferating cell nuclear antigen (PCNA), cyclin A, cyclin D1, cyclin B1, and cyclin E. Plant compounds also increase the expression of both cell cycle inhibitors, such as p53, p21, and p27, and BAD, Bax, caspase 3, caspase 7, caspase 8, and caspase 9 proteins levels. In general, this study showed that medicinal plants are potentially able to inhibit growth and proliferation of colon cancer cells. But the clinical usage of these results requires more studies on these compounds in in vivo models. Despite many studies’ in vivo models, rarely clinical trials were observed among the studies. In fact, purification of herbal compounds and demonstration of their efficacy in appropriate in vivo models, as well as clinical studies, may lead to alternative and effective ways of controlling and treating colon cancer.

Conflicts of Interest

There is no conflict of interest regarding the publication of this paper.

Authors’ Contributions

Dr. Paola Aiello and Maedeh Sharghi contributed equally to this work. Shabnam Malekpour Mansourkhani and Azam Pourabbasi Ardekan contributed equally to this work.

Acknowledgments

The authors appreciate and thank Dr. Moahammad Firouzbakht for his cooperation in draft editing.

References

  1. A. J. M. Watson and P. D. Collins, “Colon cancer: a civilization disorder,” Digestive Diseases, vol. 29, no. 2, pp. 222–228, 2011. View at: Publisher Site | Google Scholar
  2. R. R. Huxley, A. Ansary-Moghaddam, P. Clifton, S. Czernichow, C. L. Parr, and M. Woodward, “The impact of dietary and lifestyle risk factors on risk of colorectal cancer: a quantitative overview of the epidemiological evidence,” International Journal of Cancer, vol. 125, no. 1, pp. 171–180, 2009. View at: Publisher Site | Google Scholar
  3. D. J. Schultz, N. S. Wickramasinghe, M. M. Ivanova et al., “Anacardic acid inhibits estrogen receptor α–DNA binding and reduces target gene transcription and breast cancer cell proliferation,” Molecular Cancer Therapeutics, vol. 9, no. 3, pp. 594–605, 2010. View at: Publisher Site | Google Scholar
  4. L. E. Johns and R. S. Houlston, “A systematic review and meta-analysis of familial colorectal cancer risk,” The American Journal of Gastroenterology, vol. 96, no. 10, pp. 2992–3003, 2001. View at: Publisher Site | Google Scholar
  5. J. A. Meyerhardt, P. J. Catalano, D. G. Haller et al., “Impact of diabetes mellitus on outcomes in patients with colon cancer,” Journal of Clinical Oncology, vol. 21, no. 3, pp. 433–440, 2003. View at: Publisher Site | Google Scholar
  6. J. Terzić, S. Grivennikov, E. Karin, and M. Karin, “Inflammation and colon cancer,” Gastroenterology, vol. 138, no. 6, pp. 2101–2114.e5, 2010. View at: Publisher Site | Google Scholar
  7. H. J. Schmoll, E. van Cutsem, A. Stein et al., “ESMO consensus guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making,” Annals of Oncology, vol. 23, no. 10, pp. 2479–2516, 2012. View at: Publisher Site | Google Scholar
  8. M. S. O'Reilly, T. Boehm, Y. Shing et al., “Endostatin: an endogenous inhibitor of angiogenesis and tumor growth,” Cell, vol. 88, no. 2, pp. 277–285, 1997. View at: Publisher Site | Google Scholar
  9. E. Pasquier, M. Carré, B. Pourroy et al., “Antiangiogenic activity of paclitaxel is associated with its cytostatic effect, mediated by the initiation but not completion of a mitochondrial apoptotic signaling pathway,” Molecular Cancer Therapeutics, vol. 3, no. 10, pp. 1301–1310, 2004. View at: Google Scholar
  10. Board PDQATE, Colon Cancer Treatment (PDQ(R)): Health Professional Version. PDQ Cancer Information Summaries, National Cancer Institute (US), Bethesda, MD, USA, 2002.
  11. http://www.cancer.net/navigating-cancer-care/how-cancer-treated/chemotherapy/side-effects-chemotherapy.
  12. A. D. Edgar, R. Levin, C. E. Constantinou, and L. Denis, “A critical review of the pharmacology of the plant extract of Pygeum africanum in the treatment of LUTS,” Neurourology and Urodynamics, vol. 26, no. 4, pp. 458–463, 2007. View at: Publisher Site | Google Scholar
  13. J. W. Holaday and B. A. Berkowitz, “Antiangiogenic drugs: insights into drug development from endostatin, avastin and thalidomide,” Molecular Interventions, vol. 9, no. 4, pp. 157–166, 2009. View at: Publisher Site | Google Scholar
  14. W. Kooti and N. Daraei, “A review of the antioxidant activity of celery (Apium graveolens L),” Journal of Evidence-Based Complementary & Alternative Medicine, vol. 22, no. 4, pp. 1029–1034, 2017. View at: Publisher Site | Google Scholar
  15. H. Z. Marzouni, N. Daraei, N. Sharafi-Ahvazi, N. Kalani, and W. Kooti, “The effect of aqueous extract of celery leaves (Apium graveolens) on fertility in female rats,” World Journal of Pharmacy and Pharmaceutical Sciences, vol. 5, no. 5, pp. 1710–1714, 2016. View at: Google Scholar
  16. R. Sharma and S. Jain, “Cancer tretment: an overview of herbal medicines,” World Journal of Pharmacy and Pharmaceutical Sciences, vol. 3, no. 8, pp. 222–230, 2014. View at: Google Scholar
  17. M. Ghasemiboron, E. Mansori, M. Asadi-Samani et al., “Effect of ointment with cabbage, pomegranate peel, and common plantain on wound healing in male rat,” Journal of Shahrekord Uuniversity of Medical Sciences, vol. 15, no. 6, pp. 92–100, 2014. View at: Google Scholar
  18. W. Kooti, M. Ghasemiboroon, M. Asadi-Samani et al., “The effects of hydro-alcoholic extract of celery on lipid profile of rats fed a high fat diet,” Advances in Environmental Biology, vol. 8, no. 9, pp. 325–330, 2014. View at: Google Scholar
  19. A. L. Zahoor, L. Yaqoob, S. K. Shaukat, A. W. Aijaz, and I. R. Mohd, “Hepatoprotective medicinal plants used by the Gond and Bhill tribals of District Raisen Madhya Pradesh, India,” Journal of Medicinal Plants Research, vol. 9, no. 12, pp. 400–406, 2015. View at: Publisher Site | Google Scholar
  20. E. Mansouri, W. Kooti, M. Bazvand et al., “The effect of hydro-alcoholic extract of Foeniculum vulgare Mill on leukocytes and hematological tests in male rats,” Jundishapur Journal of Natural Pharmaceutical Products, vol. 10, no. 1, article e18396, 2015. View at: Publisher Site | Google Scholar
  21. S.-Y. Wu, J.-L. Shen, K.-M. Man et al., “An emerging translational model to screen potential medicinal plants for nephrolithiasis, an independent risk factor for chronic kidney disease,” Evidence-Based Complementary and Alternative Medicine, vol. 2014, Article ID 972958, 7 pages, 2014. View at: Publisher Site | Google Scholar
  22. K. Saki, M. Bahmani, M. Rafieian-Kopaei et al., “The most common native medicinal plants used for psychiatric and neurological disorders in Urmia city, northwest of Iran,” Asian Pacific Journal of Tropical Disease, vol. 4, pp. S895–S901, 2014. View at: Publisher Site | Google Scholar
  23. M. Asadi-Samani, W. Kooti, E. Aslani, and H. Shirzad, “A systematic review of Iran’s medicinal plants with anticancer effects,” Journal of Evidence-Based Complementary & Alternative Medicine, vol. 21, no. 2, pp. 143–153, 2016. View at: Publisher Site | Google Scholar
  24. A. Bishayee and G. Sethi, “Bioactive natural products in cancer prevention and therapy: progress and promise,” Seminars in Cancer Biology, vol. 40-41, pp. 1–3, 2016. View at: Publisher Site | Google Scholar
  25. K. I. Block, C. Gyllenhaal, L. Lowe et al., “Designing a broad-spectrum integrative approach for cancer prevention and treatment,” Seminars in Cancer Biology, vol. 35, pp. S276–S304, 2015. View at: Publisher Site | Google Scholar
  26. L. S. Einbond, A. Negrin, D. M. Kulakowski et al., “Traditional preparations of kava (Piper methysticum) inhibit the growth of human colon cancer cells in vitro,” Phytomedicine, vol. 24, pp. 1–13, 2017. View at: Publisher Site | Google Scholar
  27. P. Signorelli, C. Fabiani, A. Brizzolari et al., “Natural grape extracts regulate colon cancer cells malignancy,” Nutrition and Cancer, vol. 67, no. 3, pp. 494–503, 2015. View at: Publisher Site | Google Scholar
  28. A. Setiawati, H. Immanuel, and M. T. Utami, “The inhibition of Typhonium flagelliforme Lodd. Blume leaf extract on COX-2 expression of WiDr colon cancer cells,” Asian Pacific Journal of Tropical Biomedicine, vol. 6, no. 3, pp. 251–255, 2016. View at: Publisher Site | Google Scholar
  29. M. J. Jara-Palacios, D. Hernanz, T. Cifuentes-Gomez, M. L. Escudero-Gilete, F. J. Heredia, and J. P. E. Spencer, “Assessment of white grape pomace from winemaking as source of bioactive compounds, and its antiproliferative activity,” Food Chemistry, vol. 183, pp. 78–82, 2015. View at: Publisher Site | Google Scholar
  30. S. Genovese, F. Epifano, G. Carlucci, M. C. Marcotullio, M. Curini, and M. Locatelli, “Quantification of 4-geranyloxyferulic acid, a new natural colon cancer chemopreventive agent, by HPLC-DAD in grapefruit skin extract,” Journal of Pharmaceutical and Biomedical Analysis, vol. 53, no. 2, pp. 212–214, 2010. View at: Publisher Site | Google Scholar
  31. L. Reddivari, V. Charepalli, S. Radhakrishnan et al., “Grape compounds suppress colon cancer stem cells in vitro and in a rodent model of colon carcinogenesis,” BMC Complementary and Alternative Medicine, vol. 16, no. 1, p. 278, 2016. View at: Publisher Site | Google Scholar
  32. M. Dong, G. Yang, H. Liu et al., “Aged black garlic extract inhibits HT29 colon cancer cell growth via the PI3K/Akt signaling pathway,” Biomedical Reports, vol. 2, no. 2, pp. 250–254, 2014. View at: Publisher Site | Google Scholar
  33. Y. J. Oh and M. K. Sung, “Soybean saponins inhibit cell proliferation by suppressing PKC activation and induce differentiation of HT-29 human colon adenocarcinoma cells,” Nutrition and Cancer, vol. 39, no. 1, pp. 132–138, 2001. View at: Publisher Site | Google Scholar
  34. H.-Y. Kim, R. Yu, J.-S. Kim, Y.-K. Kim, and M.-K. Sung, “Antiproliferative crude soy saponin extract modulates the expression of IκBα, protein kinase C, and cyclooxygenase-2 in human colon cancer cells,” Cancer Letters, vol. 210, no. 1, pp. 1–6, 2004. View at: Publisher Site | Google Scholar
  35. F. Hajiaghaalipour, M. S. Kanthimathi, J. Sanusi, and J. Rajarajeswaran, “White tea (Camellia sinensis) inhibits proliferation of the colon cancer cell line, HT-29, activates caspases and protects DNA of normal cells against oxidative damage,” Food Chemistry, vol. 169, pp. 401–410, 2015. View at: Publisher Site | Google Scholar
  36. A. Gosslau, D. L. En Jao, M.-T. Huang et al., “Effects of the black tea polyphenol theaflavin-2 on apoptotic and inflammatory pathways in vitro and in vivo,” Molecular Nutrition & Food Research, vol. 55, no. 2, pp. 198–208, 2011. View at: Publisher Site | Google Scholar
  37. S. Y. Park, E. J. Kim, H. J. Choi et al., “Anti-carcinogenic effects of non-polar components containing licochalcone A in roasted licorice root,” Nutrition Research and Practice, vol. 8, no. 3, pp. 257–266, 2014. View at: Publisher Site | Google Scholar
  38. F. Naselli, L. Tesoriere, F. Caradonna et al., “Anti-proliferative and pro-apoptotic activity of whole extract and isolated indicaxanthin from Opuntia ficus-indica associated with re-activation of the onco-suppressor p16INK4a gene in human colorectal carcinoma (Caco-2) cells,” Biochemical and Biophysical Research Communications, vol. 450, no. 1, pp. 652–658, 2014. View at: Publisher Site | Google Scholar
  39. P. L. Ng, N. F. Rajab, S. M. Then et al., “Piper betle leaf extract enhances the cytotoxicity effect of 5-fluorouracil in inhibiting the growth of HT29 and HCT116 colon cancer cells,” Journal of Zhejiang University-SCIENCE B, vol. 15, no. 8, pp. 692–700, 2014. View at: Publisher Site | Google Scholar
  40. M. E. Olsson, C. S. Andersson, S. Oredsson, R. H. Berglund, and K. E. Gustavsson, “Antioxidant levels and inhibition of cancer cell proliferation in vitro by extracts from organically and conventionally cultivated strawberries,” Journal of Agricultural and Food Chemistry, vol. 54, no. 4, pp. 1248–1255, 2006. View at: Publisher Site | Google Scholar
  41. S. J. Min, J. Y. Lim, H. R. Kim, S. J. Kim, and Y. Kim, “Sasa quelpaertensis leaf extract inhibits colon cancer by regulating cancer cell stemness in vitro and in vivo,” International Journal of Molecular Sciences, vol. 16, no. 12, pp. 9976–9997, 2015. View at: Publisher Site | Google Scholar
  42. Q. Zhao, X. C. Huo, F. D. Sun, and R. Q. Dong, “Polyphenol-rich extract of Salvia chinensis exhibits anticancer activity in different cancer cell lines, and induces cell cycle arrest at the G0/G1-phase, apoptosis and loss of mitochondrial membrane potential in pancreatic cancer cells,” Molecular Medicine Reports, vol. 12, no. 4, pp. 4843–4850, 2015. View at: Publisher Site | Google Scholar
  43. L. S. Adams, N. P. Seeram, B. B. Aggarwal, Y. Takada, D. Sand, and D. Heber, “Pomegranate juice, total pomegranate ellagitannins, and punicalagin suppress inflammatory cell signaling in colon cancer cells,” Journal of Agricultural and Food Chemistry, vol. 54, no. 3, pp. 980–985, 2006. View at: Publisher Site | Google Scholar
  44. S. Đurđević, K. Šavikin, J. Živković et al., “Antioxidant and cytotoxic activity of fatty oil isolated by supercritical fluid extraction from microwave pretreated seeds of wild growing Punica granatum L.,” The Journal of Supercritical Fluids, vol. 133, no. 1, pp. 225–232, 2018. View at: Publisher Site | Google Scholar
  45. T. S. Thind, S. K. Agrawal, A. K. Saxena, and S. Arora, “Studies on cytotoxic, hydroxyl radical scavenging and topoisomerase inhibitory activities of extracts of Tabernaemontana divaricata (L.) R.Br. ex Roem. and Schult,” Food and Chemical Toxicology, vol. 46, no. 8, pp. 2922–2927, 2008. View at: Publisher Site | Google Scholar
  46. S. Tansuwanwong, H. Yamamoto, K. Imai, and U. Vinitketkumnuen, “Antiproliferation and apoptosis on RKO colon cancer by Millingtonia hortensis,” Plant Foods for Human Nutrition, vol. 64, no. 1, pp. 11–17, 2009. View at: Publisher Site | Google Scholar
  47. E. M. Coates, G. Popa, C. I. R. Gill et al., “Colon-available raspberry polyphenols exhibit anti-cancer effects on in vitro models of colon cancer,” Journal of Carcinogenesis, vol. 6, no. 1, p. 4, 2007. View at: Publisher Site | Google Scholar
  48. J. God, P. L. Tate, and L. L. Larcom, “Red raspberries have antioxidant effects that play a minor role in the killing of stomach and colon cancer cells,” Nutrition Research, vol. 30, no. 11, pp. 777–782, 2010. View at: Publisher Site | Google Scholar
  49. K. Dimas, C. Tsimplouli, C. Houchen et al., “An ethanol extract of Hawaiian turmeric: extensive in vitro anticancer activity against human colon cancer cells,” Alternative Therapies in Health and Medicine, vol. 21, Supplement 2, pp. 46–54, 2015. View at: Google Scholar
  50. S. A. Cichello, Q. Yao, A. Dowell, B. Leury, and X. Q. He, “Proliferative and inhibitory activity of Siberian ginseng (Eleutherococcus senticosus) extract on cancer cell lines; A-549, XWLC-05, HCT-116, CNE and Beas-2b,” Asian Pacific Journal of Cancer Prevention, vol. 16, no. 11, pp. 4781–4786, 2015. View at: Publisher Site | Google Scholar
  51. S. Tansuwanwong, Y. Hiroyuki, I. Kohzoh, and U. Vinitketkumnuen, “Induction of apoptosis in RKO colon cancer cell line by an aqueous extract of Millingtonia hortensis,” Asian Pacific Journal of Cancer Prevention, vol. 7, no. 4, pp. 641–644, 2006. View at: Google Scholar
  52. R. Chatthongpisut, S. J. Schwartz, and J. Yongsawatdigul, “Antioxidant activities and antiproliferative activity of Thai purple rice cooked by various methods on human colon cancer cells,” Food Chemistry, vol. 188, pp. 99–105, 2015. View at: Publisher Site | Google Scholar
  53. S. Z. Moghadamtousi, H. Karimian, E. Rouhollahi, M. Paydar, M. Fadaeinasab, and H. Abdul Kadir, “Annona muricata leaves induce G1 cell cycle arrest and apoptosis through mitochondria-mediated pathway in human HCT-116 and HT-29 colon cancer cells,” Journal of Ethnopharmacology, vol. 156, pp. 277–289, 2014. View at: Publisher Site | Google Scholar
  54. N. J. Jacobo-Herrera, F. E. Jacobo-Herrera, A. Zentella-Dehesa, A. Andrade-Cetto, M. Heinrich, and C. Perez-Plasencia, “Medicinal plants used in Mexican traditional medicine for the treatment of colorectal cancer,” Journal of Ethnopharmacology, vol. 179, pp. 391–402, 2016. View at: Publisher Site | Google Scholar
  55. K. V. Balan, J. Prince, Z. Han et al., “Antiproliferative activity and induction of apoptosis in human colon cancer cells treated in vitro with constituents of a product derived from Pistacia lentiscus L. var. chia,” Phytomedicine, vol. 14, no. 4, pp. 263–272, 2007. View at: Publisher Site | Google Scholar
  56. K. V. Balan, C. Demetzos, J. Prince et al., “Induction of apoptosis in human colon cancer HCT116 cells treated with an extract of the plant product, Chios mastic gum,” In Vivo, vol. 19, no. 1, pp. 93–102, 2005. View at: Google Scholar
  57. M. L. King and L. L. Murphy, “Role of cyclin inhibitor protein p21 in the inhibition of HCT116 human colon cancer cell proliferation by American ginseng (Panax quinquefolius) and its constituents,” Phytomedicine, vol. 17, no. 3-4, pp. 261–268, 2010. View at: Publisher Site | Google Scholar
  58. V. Charepalli, L. Reddivari, S. Radhakrishnan, R. Vadde, R. Agarwal, and J. K. P. Vanamala, “Anthocyanin-containing purple-fleshed potatoes suppress colon tumorigenesis via elimination of colon cancer stem cells,” The Journal of Nutritional Biochemistry, vol. 26, no. 12, pp. 1641–1649, 2015. View at: Publisher Site | Google Scholar
  59. R. Campos-Vega, R. G. Guevara-Gonzalez, B. L. Guevara-Olvera, B. Dave Oomah, and G. Loarca-Piña, “Bean (Phaseolus vulgaris L.) polysaccharides modulate gene expression in human colon cancer cells (HT-29),” Food Research International, vol. 43, no. 4, pp. 1057–1064, 2010. View at: Publisher Site | Google Scholar
  60. A. T. Serra, J. Poejo, A. A. Matias, M. R. Bronze, and C. M. M. Duarte, “Evaluation of Opuntia spp. derived products as antiproliferative agents in human colon cancer cell line (HT29),” Food Research International, vol. 54, no. 1, pp. 892–901, 2013. View at: Publisher Site | Google Scholar
  61. T. dos Santos, C. Tavares, D. Sousa et al., “Suillus luteus methanolic extract inhibits cell growth and proliferation of a colon cancer cell line,” Food Research International, vol. 53, no. 1, pp. 476–481, 2013. View at: Publisher Site | Google Scholar
  62. G. K. Jayaprakasha, K. K. Mandadi, S. M. Poulose, Y. Jadegoud, G. A. Nagana Gowda, and B. S. Patil, “Inhibition of colon cancer cell growth and antioxidant activity of bioactive compounds from Poncirus trifoliata (L.) Raf,” Bioorganic & Medicinal Chemistry, vol. 15, no. 14, pp. 4923–4932, 2007. View at: Publisher Site | Google Scholar
  63. M. González-Vallinas, S. Molina, G. Vicente et al., “Antitumor effect of 5-fluorouracil is enhanced by rosemary extract in both drug sensitive and resistant colon cancer cells,” Pharmacological Research, vol. 72, pp. 61–68, 2013. View at: Publisher Site | Google Scholar
  64. A. Valdés, G. Sullini, E. Ibáñez, A. Cifuentes, and V. García-Cañas, “Rosemary polyphenols induce unfolded protein response and changes in cholesterol metabolism in colon cancer cells,” Journal of Functional Foods, vol. 15, pp. 429–439, 2015. View at: Publisher Site | Google Scholar
  65. A. Valdes, K. A. Artemenko, J. Bergquist, V. Garcia-Canas, and A. Cifuentes, “Comprehensive proteomic study of the antiproliferative activity of a polyphenol-enriched rosemary extract on colon cancer cells using nanoliquid chromatography–orbitrap MS/MS,” Journal of Proteome Research, vol. 15, no. 6, pp. 1971–1985, 2016. View at: Publisher Site | Google Scholar
  66. A. Pérez-Sánchez, N. Sánchez-Marzo, M. Herranz-López, E. Barrajón-Catalán, and V. Micol, “Rosemary (Rosmarinus officinalis L) extract increases ROS and modulates Nrf2 pathway in human colon cancer cell lines,” Free Radical Biology & Medicine, vol. 108, p. S79, 2017. View at: Publisher Site | Google Scholar
  67. Y. R. Um, C.-S. Kong, J. I. Lee, Y. A. Kim, T. J. Nam, and Y. Seo, “Evaluation of chemical constituents from Glehnia littoralis for antiproliferative activity against HT-29 human colon cancer cells,” Process Biochemistry, vol. 45, no. 1, pp. 114–119, 2010. View at: Publisher Site | Google Scholar
  68. M. A. Encalada, S. Rehecho, D. Ansorena, I. Astiasarán, R. Y. Cavero, and M. I. Calvo, “Antiproliferative effect of phenylethanoid glycosides from Verbena officinalis L. on colon cancer cell lines,” LWT - Food Science and Technology, vol. 63, no. 2, pp. 1016–1022, 2015. View at: Publisher Site | Google Scholar
  69. Y. Nakamura, Y. Hasegawa, K. Shirota et al., “Differentiation-inducing effect of piperitenone oxide, a fragrant ingredient of spearmint (Mentha spicata), but not carvone and menthol, against human colon cancer cells,” Journal of Functional Foods, vol. 8, pp. 62–67, 2014. View at: Publisher Site | Google Scholar
  70. A. Panyathep, T. Chewonarin, K. Taneyhill, Y.-J. Surh, and U. Vinitketkumnuen, “Effects of dried longan seed (Euphoria longana Lam.) extract on VEGF secretion and expression in colon cancer cells and angiogenesis in human umbilical vein endothelial cells,” Journal of Functional Foods, vol. 5, no. 3, pp. 1088–1096, 2013. View at: Publisher Site | Google Scholar
  71. G. Leisching, B. Loos, T. Nell, and A. M. Engelbrecht, “Sutherlandia frutescens treatment induces apoptosis and modulates the PI3-kinase pathway in colon cancer cells,” South African Journal of Botany, vol. 100, pp. 20–26, 2015. View at: Publisher Site | Google Scholar
  72. C. Weidner, M. Rousseau, A. Plauth et al., “Melissa officinalis extract induces apoptosis and inhibits proliferation in colon cancer cells through formation of reactive oxygen species,” Phytomedicine, vol. 22, no. 2, pp. 262–270, 2015. View at: Publisher Site | Google Scholar
  73. C.-Y. Wang, T.-C. Wu, S.-L. Hsieh, Y.-H. Tsai, C.-W. Yeh, and C.-Y. Huang, “Antioxidant activity and growth inhibition of human colon cancer cells by crude and purified fucoidan preparations extracted from Sargassum cristaefolium,” Journal of Food and Drug Analysis, vol. 23, no. 4, pp. 766–777, 2015. View at: Publisher Site | Google Scholar
  74. J. Lin, Q. Li, H. Chen, H. Lin, Z. Lai, and J. Peng, “Hedyotis diffusa Willd. extract suppresses proliferation and induces apoptosis via IL-6-inducible STAT3 pathway inactivation in human colorectal cancer cells,” Oncology Letters, vol. 9, no. 4, pp. 1962–1970, 2015. View at: Publisher Site | Google Scholar
  75. M. Marrelli, F. Menichini, and F. Conforti, “A comparative study of Zingiber officinale Roscoe pulp and peel: phytochemical composition and evaluation of antitumour activity,” Natural Product Research, vol. 29, no. 21, pp. 2045–2049, 2015. View at: Publisher Site | Google Scholar
  76. D. Goh, Y. H. Lee, and E. S. Ong, “Inhibitory effects of a chemically standardized extract from Scutellaria barbata in human colon cancer cell lines, LoVo,” Journal of Agricultural and Food Chemistry, vol. 53, no. 21, pp. 8197–8204, 2005. View at: Publisher Site | Google Scholar
  77. S. A. Kang, H. J. Park, M.-J. Kim, S.-Y. Lee, S.-W. Han, and K.-H. Leem, “Citri Reticulatae Viride Pericarpium extract induced apoptosis in SNU-C4, human colon cancer cells,” Journal of Ethnopharmacology, vol. 97, no. 2, pp. 231–235, 2005. View at: Publisher Site | Google Scholar
  78. A. Chicca, B. Adinolfi, E. Martinotti et al., “Cytotoxic effects of Echinacea root hexanic extracts on human cancer cell lines,” Journal of Ethnopharmacology, vol. 110, no. 1, pp. 148–153, 2007. View at: Publisher Site | Google Scholar
  79. L. A. Boyd, M. J. McCann, Y. Hashim, R. N. Bennett, C. I. R. Gill, and I. R. Rowland, “Assessment of the anti-genotoxic, anti-proliferative, and anti-metastatic potential of crude watercress extract in human colon cancer cells,” Nutrition and Cancer, vol. 55, no. 2, pp. 232–241, 2006. View at: Publisher Site | Google Scholar
  80. J. Gwak, S. Park, M. Cho et al., “Polysiphonia japonica extract suppresses the Wnt/β-catenin pathway in colon cancer cells by activation of NF-κB,” International Journal of Molecular Medicine, vol. 17, pp. 1005–1010, 2006. View at: Publisher Site | Google Scholar
  81. C. Li and M.-H. Wang, “Aristolochia debilis Sieb. et Zucc. induces apoptosis and reactive oxygen species in the HT-29 human colon cancer cell line,” Cancer Biotherapy and Radiopharmaceuticals, vol. 28, no. 10, pp. 717–724, 2013. View at: Publisher Site | Google Scholar
  82. A. F. A. Aisha, Z. Ismail, K. M. Abu-Salah, J. M. Siddiqui, G. Ghafar, and A. M. S. Abdul Majid, “Syzygium campanulatum korth methanolic extract inhibits angiogenesis and tumor growth in nude mice,” BMC Complementary and Alternative Medicine, vol. 13, no. 1, 2013. View at: Publisher Site | Google Scholar
  83. W. Lin, L. Zheng, Q. Zhuang et al., “Spica prunellae promotes cancer cell apoptosis, inhibits cell proliferation and tumor angiogenesis in a mouse model of colorectal cancer via suppression of stat3 pathway,” BMC Complementary and Alternative Medicine, vol. 13, no. 1, 2013. View at: Publisher Site | Google Scholar
  84. L. Maness, I. Goktepe, H. Chen, M. Ahmedna, and S. Sang, “Impact of Phytolacca americana extracts on gene expression of colon cancer cells,” Phytotherapy Research, vol. 28, no. 2, pp. 219–223, 2014. View at: Publisher Site | Google Scholar
  85. M. Deepa, T. Sureshkumar, P. K. Satheeshkumar, and S. Priya, “Antioxidant rich Morus alba leaf extract induces apoptosis in human colon and breast cancer cells by the downregulation of nitric oxide produced by inducible nitric oxide synthase,” Nutrition and Cancer, vol. 65, no. 2, pp. 305–310, 2013. View at: Publisher Site | Google Scholar
  86. R. Senthilkumar, T. Parimelazhagan, O. P. Chaurasia, and R. B. Srivastava, “Free radical scavenging property and antiproliferative activity of Rhodiola imbricata Edgew extracts in HT-29 human colon cancer cells,” Asian Pacific Journal of Tropical Medicine, vol. 6, no. 1, pp. 11–19, 2013. View at: Publisher Site | Google Scholar
  87. S.-M. Oh, J. Kim, J. Lee et al., “Anticancer potential of an ethanol extract of Asiasari radix against HCT-116 human colon cancer cells in vitro,” Oncology Letters, vol. 5, no. 1, pp. 305–310, 2013. View at: Publisher Site | Google Scholar
  88. E. L. Symonds, I. Konczak, and M. Fenech, “The Australian fruit Illawarra plum (Podocarpus elatus Endl., Podocarpaceae) inhibits telomerase, increases histone deacetylase activity and decreases proliferation of colon cancer cells,” British Journal of Nutrition, vol. 109, no. 12, pp. 2117–2125, 2013. View at: Publisher Site | Google Scholar
  89. Y. L. Tsai, C. C. Chiu, J. Yi-Fu Chen, K. C. Chan, and S. D. Lin, “Cytotoxic effects of Echinacea purpurea flower extracts and cichoric acid on human colon cancer cells through induction of apoptosis,” Journal of Ethnopharmacology, vol. 143, no. 3, pp. 914–919, 2012. View at: Publisher Site | Google Scholar
  90. S.-J. Lee, K. Park, S.-D. Ha, W.-J. Kim, and S.-K. Moon, “Gleditsia sinensis thorn extract inhibits human colon cancer cells: the role of ERK1/2, G2/MPhase cell cycle arrest and p53 expression,” Phytotherapy Research, vol. 24, no. 12, pp. 1870–1876, 2010. View at: Publisher Site | Google Scholar
  91. S. J. Lee, Y. H. Cho, H. Kim et al., “Inhibitory effects of the ethanol extract of Gleditsia sinensis thorns on human colon cancer HCT116 cells in vitro and in vivo,” Oncology Reports, vol. 22, no. 6, pp. 1505–1512, 2009. View at: Publisher Site | Google Scholar
  92. N. Kosem, K. Ichikawa, H. Utsumi, and P. Moongkarndi, “In vivo toxicity and antitumor activity of mangosteen extract,” Journal of Natural Medicines, vol. 67, no. 2, pp. 255–263, 2013. View at: Publisher Site | Google Scholar
  93. A.-R. Han, J.-A. Kim, D. D. Lantvit et al., “Cytotoxic xanthone constituents of the stem bark of Garcinia mangostana (mangosteen),” Journal of Natural Products, vol. 72, no. 11, pp. 2028–2031, 2009. View at: Publisher Site | Google Scholar
  94. J.-f. Zhang, M.-l. He, Qi Dong et al., “Aqueous extracts of Fructus Ligustri Lucidi enhance the sensitivity of human colorectal carcinoma DLD-1 cells to doxorubicin-induced apoptosis via Tbx3 suppression,” Integrative Cancer Therapies, vol. 10, no. 1, pp. 85–91, 2011. View at: Publisher Site | Google Scholar
  95. A. Hematulin, K. Ingkaninan, N. Limpeanchob, and D. Sagan, “Ethanolic extract from Derris scandens Benth mediates radiosensitzation via two distinct modes of cell death in human colon cancer HT-29 cells,” Asian Pacific Journal of Cancer Prevention, vol. 15, no. 4, pp. 1871–1877, 2014. View at: Publisher Site | Google Scholar
  96. E. Ribeiro-Varandas, F. Ressurreição, W. Viegas, and M. Delgado, “Cytotoxicity of Eupatorium cannabinum L. ethanolic extract against colon cancer cells and interactions with bisphenol A and doxorubicin,” BMC Complementary and Alternative Medicine, vol. 14, no. 1, 2014. View at: Publisher Site | Google Scholar
  97. A. R. Massey, L. Reddivari, and J. Vanamala, “The dermal layer of sweet sorghum (Sorghum bicolor) stalk, a byproduct of biofuel production and source of unique 3-deoxyanthocyanidins, has more antiproliferative and proapoptotic activity than the pith in p53 variants of HCT116 and colon cancer stem cells,” Journal of Agricultural and Food Chemistry, vol. 62, no. 14, pp. 3150–3159, 2014. View at: Publisher Site | Google Scholar
  98. A. R. Massey, L. Reddivari, S. Radhakrishnan et al., “Pro-apoptotic activity against cancer stem cells differs between different parts of sweet sorghum,” Journal of Functional Foods, vol. 23, pp. 601–613, 2016. View at: Publisher Site | Google Scholar
  99. Y. H. Wong, W. Y. Tan, C. P. Tan, K. Long, and K. L. Nyam, “Cytotoxic activity of kenaf (Hibiscus cannabinus L.) seed extract and oil against human cancer cell lines,” Asian Pacific Journal of Tropical Biomedicine, vol. 4, Supplement 1, pp. S510–S515, 2014. View at: Publisher Site | Google Scholar
  100. S. Enayat, M. S. Ceyhan, A. A. Basaran, M. Gursel, and S. Banerjee, “Anticarcinogenic effects of the ethanolic extract of Salix aegyptiaca in colon cancer cells: involvement of Akt/PKB and MAPK pathways,” Nutrition and Cancer, vol. 65, no. 7, pp. 1045–1058, 2013. View at: Publisher Site | Google Scholar
  101. E. J. Kim, Y.-J. Lee, H.-K. Shin, and J. H. Y. Park, “Induction of apoptosis by the aqueous extract of Rubus coreanum in HT-29 human colon cancer cells,” Nutrition, vol. 21, no. 11-12, pp. 1141–1148, 2005. View at: Publisher Site | Google Scholar
  102. L. Wang, M. L. Xu, J. H. Hu, S. K. Rasmussen, and M.-H. Wang, “Codonopsis lanceolata extract induces G0/G1 arrest and apoptosis in human colon tumor HT-29 cells – involvement of ROS generation and polyamine depletion,” Food and Chemical Toxicology, vol. 49, no. 1, pp. 149–154, 2011. View at: Publisher Site | Google Scholar
  103. S. Sang, J. Hong, H. Wu et al., “Increased growth inhibitory effects on human cancer cells and anti-inflammatory potency of shogaols from Zingiber officinale relative to gingerols,” Journal of Agricultural and Food Chemistry, vol. 57, no. 22, pp. 10645–10650, 2009. View at: Publisher Site | Google Scholar
  104. J. S. Lee, S.-Y. Park, D. Thapa et al., “Grifola frondosa water extract alleviates intestinal inflammation by suppressing TNF-α production and its signaling,” Experimental and Molecular Medicine, vol. 42, no. 2, pp. 143–154, 2010. View at: Publisher Site | Google Scholar
  105. N. B. Janakiram, A. Mohammed, Y. Zhang et al., “Chemopreventive effects of Frondanol A5, a Cucumaria frondosa extract, against rat colon carcinogenesis and inhibition of human colon cancer cell growth,” Cancer Prevention Research, vol. 3, no. 1, pp. 82–91, 2010. View at: Publisher Site | Google Scholar
  106. L. Pan, D. D. Lantvit, S. Riswan et al., “Bioactivity-guided isolation of cytotoxic sesquiterpenes of Rolandra fruticosa,” Phytochemistry, vol. 71, no. 5-6, pp. 635–640, 2010. View at: Publisher Site | Google Scholar
  107. M. Carvalho, B. M. Silva, R. Silva, P.́. Valentão, P. B. Andrade, and M. L. Bastos, “First report on Cydonia oblonga Miller anticancer potential: differential antiproliferative effect against human kidney and colon cancer cells,” Journal of Agricultural and Food Chemistry, vol. 58, no. 6, pp. 3366–3370, 2010. View at: Publisher Site | Google Scholar
  108. J. A. Kim, E. Lau, D. Tay, and E. J. C. de Blanco, “Antioxidant and NF-κB inhibitory constituents isolated from Morchella esculenta,” Natural Product Research, vol. 25, no. 15, pp. 1412–1417, 2011. View at: Publisher Site | Google Scholar
  109. J. E. Kim, W. Y. Chung, K. S. Chun et al., “Pleurospermum kamtschaticum extract induces apoptosis via mitochondrial pathway and NAG-1 expression in colon cancer cells,” Bioscience, Biotechnology, and Biochemistry, vol. 74, no. 4, pp. 788–792, 2014. View at: Publisher Site | Google Scholar
  110. S. C. W. Sze, K. L. Wong, W. K. Liu et al., “Regulation of p21, MMP-1, and MDR-1 expression in human colon carcinoma HT29 cells by Tian Xian Liquid, a Chinese medicinal formula, in vitro and in vivo,” Integrative Cancer Therapies, vol. 10, no. 1, pp. 58–69, 2011. View at: Publisher Site | Google Scholar
  111. D. S. Ryu, G. O. Baek, E. Y. Kim, K. H. Kim, and D. S. Lee, “Effects of polysaccharides derived from Orostachys japonicus on induction of cell cycle arrest and apoptotic cell death in human colon cancer cells,” BMB Reports, vol. 43, no. 11, pp. 750–755, 2010. View at: Publisher Site | Google Scholar
  112. X.-H. Chen, Y.-X. Miao, X.-J. Wang et al., “Effects of Ginkgo biloba extract EGb761 on human colon adenocarcinoma cells,” Cellular Physiology and Biochemistry, vol. 27, no. 3-4, pp. 227–232, 2011. View at: Publisher Site | Google Scholar
  113. E. A. Hudson, P. A. Dinh, T. Kokubun, M. S. Simmonds, and A. Gescher, “Characterization of potentially chemopreventive phenols in extracts of brown rice that inhibit the growth of human breast and colon cancer cells,” Cancer Epidemiology, Biomarkers & Prevention, vol. 9, pp. 1163–1170, 2000. View at: Google Scholar
  114. J. de la Cruz, D. H. Kim, and S. G. Hwang, “Anti cancer effects of Cnidium officinale Makino extract mediated through apoptosis and cell cycle arrest in the HT-29 human colorectal cancer cell line,” Asian Pacific Journal of Cancer Prevention : APJCP, vol. 15, no. 13, pp. 5117–5121, 2014. View at: Google Scholar
  115. K.-S. Nam, B. G. Ha, and Y. H. Shon, “Effect of Cnidii Rhizoma on nitric oxide production and invasion of human colorectal adenocarcinoma HT-29 cells,” Oncology Letters, vol. 9, no. 1, pp. 483–487, 2015. View at: Publisher Site | Google Scholar
  116. P. Ovadje, D. Ma, P. Tremblay et al., “Evaluation of the efficacy & biochemical mechanism of cell death induction by Piper longum extract selectively in in-vitro and in-vivo models of human cancer cells,” PLoS One, vol. 9, no. 11, article e113250, 2014. View at: Publisher Site | Google Scholar
  117. S. Arora and S. Tandon, “Achyranthes aspera root extracts induce human colon cancer cell (COLO-205) death by triggering the mitochondrial apoptosis pathway and S phase cell cycle arrest,” The Scientific World Journal, vol. 2014, Article ID 129697, 15 pages, 2014. View at: Publisher Site | Google Scholar
  118. A. al-Menhali, A. al-Rumaihi, H. al-Mohammed et al., “Thymus vulgaris (thyme) inhibits proliferation, adhesion, migration, and invasion of human colorectal cancer cells,” Journal of Medicinal Food, vol. 18, no. 1, pp. 54–59, 2015. View at: Publisher Site | Google Scholar
  119. K. A. Kang, J. K. Kim, Y. J. Jeong, S.-Y. Na, and J. W. Hyun, “Dictyopteris undulata extract induces apoptosis via induction of endoplasmic reticulum stress in human colon cancer cells,” Journal of Cancer Prevention, vol. 19, no. 2, pp. 118–124, 2014. View at: Publisher Site | Google Scholar
  120. X. Zhao, P. Sun, Y. Qian, and H. Suo, “D. candidum has in vitro anticancer effects in HCT-116 cancer cells and exerts in vivo anti-metastatic effects in mice,” Nutrition Research and Practice, vol. 8, no. 5, pp. 487–493, 2014. View at: Publisher Site | Google Scholar
  121. B. Romano, F. Borrelli, E. Pagano, M. G. Cascio, R. G. Pertwee, and A. A. Izzo, “Inhibition of colon carcinogenesis by a standardized Cannabis sativa extract with high content of cannabidiol,” Phytomedicine, vol. 21, no. 5, pp. 631–639, 2014. View at: Publisher Site | Google Scholar
  122. N. Eid, S. Enani, G. Walton et al., “The impact of date palm fruits and their component polyphenols, on gut microbial ecology, bacterial metabolites and colon cancer cell proliferation,” Journal of Nutritional Science, vol. 3, no. 46, pp. 1–9, 2014. View at: Publisher Site | Google Scholar
  123. X.-L. Tang, X. Y. Yang, Y. C. Kim et al., “Protective effects of the ethanolic extract of Melia toosendan fruit against colon cancer,” Indian Journal of Biochemistry & Biophysics, vol. 49, no. 3, pp. 173–181, 2012. View at: Google Scholar
  124. K. Bajbouj, J. Schulze-Luehrmann, S. Diermeier, A. Amin, and R. Schneider-Stock, “The anticancer effect of saffron in two p53 isogenic colorectal cancer cell lines,” BMC Complementary and Alternative Medicine, vol. 12, no. 1, 2012. View at: Publisher Site | Google Scholar
  125. R. Sánchez-Vioque, O. Santana-Méridas, M. Polissiou et al., “Polyphenol composition and in vitro antiproliferative effect of corm, tepal and leaf from Crocus sativus L. on human colon adenocarcinoma cells (Caco-2),” Journal of Functional Foods, vol. 24, pp. 18–25, 2016. View at: Publisher Site | Google Scholar
  126. L.-H. Shang, C.-M. Li, Z.-Y. Yang, D.-H. Che, J.-Y. Cao, and Y. Yu, “Luffa echinata Roxb. induces human colon cancer cell (HT-29) death by triggering the mitochondrial apoptosis pathway,” Molecules, vol. 17, no. 5, pp. 5780–5794, 2012. View at: Publisher Site | Google Scholar
  127. G. Angel-Morales, G. Noratto, and S. Mertens-Talcott, “Red wine polyphenolics reduce the expression of inflammation markers in human colon-derived CCD-18Co myofibroblast cells: potential role of microRNA-126,” Food & Function, vol. 3, no. 7, pp. 745–752, 2012. View at: Publisher Site | Google Scholar
  128. A. T. Choumessi, M. Danel, S. Chassaing et al., “Characterization of the antiproliferative activity of Xylopia aethiopica,” Cell Division, vol. 7, no. 1, pp. 8–8, 2012. View at: Publisher Site | Google Scholar
  129. L. Yang, K. F. Allred, B. Geera, C. D. Allred, and J. M. Awika, “Sorghum phenolics demonstrate estrogenic action and induce apoptosis in nonmalignant colonocytes,” Nutrition and Cancer, vol. 64, no. 3, pp. 419–427, 2012. View at: Publisher Site | Google Scholar
  130. C. Mazewski, K. Liang, and E. Gonzalez de Mejia, “Comparison of the effect of chemical composition of anthocyanin-rich plant extracts on colon cancer cell proliferation and their potential mechanism of action using in vitro, in silico, and biochemical assays,” Food Chemistry, vol. 242, pp. 378–388, 2018. View at: Publisher Site | Google Scholar
  131. N.-W. He, Y. Zhao, L. Guo, J. Shang, and X.-B. Yang, “Antioxidant, antiproliferative, and pro-apoptotic activities of a saponin extract derived from the roots of Panax notoginseng (Burk.) F.H. Chen,” Journal of Medicinal Food, vol. 15, no. 4, pp. 350–359, 2012. View at: Publisher Site | Google Scholar
  132. F. A. Hashem, H. Motawea, A. E. el-Shabrawy, K. Shaker, and S. el-Sherbini, “Myrosinase hydrolysates of Brassica oleraceae L. var. italica reduce the risk of colon cancer,” Phytotherapy Research, vol. 26, no. 5, pp. 743–747, 2012. View at: Publisher Site | Google Scholar
  133. Y. Jia, Q. Guan, Y. Guo, and C. du, “Reduction of inflammatory hyperplasia in the intestine in colon cancer-prone mice by water-extract of Cistanche deserticola,” Phytotherapy Research, vol. 26, no. 6, pp. 812–819, 2012. View at: Publisher Site | Google Scholar
  134. S. Gorlach, W. Wagner, A. Podsędek, K. Szewczyk, M. Koziołkiewicz, and J. Dastych, “Procyanidins from Japanese quince (Chaenomeles japonica) fruit induce apoptosis in human colon cancer Caco-2 cells in a degree of polymerization-dependent manner,” Nutrition and Cancer, vol. 63, no. 8, pp. 1348–1360, 2011. View at: Publisher Site | Google Scholar
  135. S. Mori, T. Sawada, T. Okada, T. Ohsawa, M. Adachi, and K. Keiichi, “New anti-proliferative agent, MK615, from Japanese apricot “Prunus mume” induces striking autophagy in colon cancer cells in vitro,” World Journal of Gastroenterology, vol. 13, no. 48, pp. 6512–6517, 2007. View at: Publisher Site | Google Scholar
  136. S. C. Hsu, J. H. Lu, C. L. Kuo et al., “Crude extracts of Solanum lyratum induced cytotoxicity and apoptosis in a human colon adenocarcinoma cell line (Colo 205),” Anticancer Research, vol. 28, no. 2A, pp. 1045–1054, 2008. View at: Google Scholar
  137. N. el-Najjar, N. Saliba, S. Talhouk, and H. Gali-Muhtasib, “Onopordum cynarocephalum induces apoptosis and protects against 1,2 dimethylhydrazine-induced colon cancer,” Oncology Reports, vol. 17, no. 6, pp. 1517–1523, 2007. View at: Google Scholar
  138. X. Li, T. Ohtsuki, T. Koyano, T. Kowithayakorn, and M. Ishibashi, “New Wnt/β-catenin signaling inhibitors isolated from Eleutherine palmifolia,” Chemistry, vol. 4, no. 4, pp. 540–547, 2009. View at: Publisher Site | Google Scholar
  139. S. Jaramillo, F. J. G. Muriana, R. Guillen, A. Jimenez-Araujo, R. Rodriguez-Arcos, and S. Lopez, “Saponins from edible spears of wild asparagus inhibit AKT, p70S6K, and ERK signalling, and induce apoptosis through G0/G1 cell cycle arrest in human colon cancer HCT-116 cells,” Journal of Functional Foods, vol. 26, pp. 1–10, 2016. View at: Publisher Site | Google Scholar
  140. R. Vadde, S. Radhakrishnan, H. Eranda Karunathilake Kurundu, L. Reddivari, and J. K. P. Vanamala, “Indian gooseberry (Emblica officinalis Gaertn.) suppresses cell proliferation and induces apoptosis in human colon cancer stem cells independent of p53 status via suppression of c-Myc and cyclin D1,” Journal of Functional Foods, vol. 25, pp. 267–278, 2016. View at: Publisher Site | Google Scholar
  141. L. Ai, Y.-C. Chung, K.-C. G. Jeng et al., “Antioxidant hydrocolloids from herb Graptopetalum paraguayense leaves show anti-colon cancer cells and anti-neuroinflammatory potentials,” Food Hydrocolloids, vol. 73, pp. 51–59, 2017. View at: Publisher Site | Google Scholar
  142. N. Polachi, B. Subramaniyan, P. Nagaraja, K. Rangiah, and M. Ganeshan, “Extract from Butea monosperma inhibits β-catenin/Tcf signaling in SW480 human colon cancer cells,” Gene Reports, vol. 10, pp. 79–89, 2018. View at: Publisher Site | Google Scholar
  143. P. Zhu, Y. Wu, A. Yang, X. Fu, M. Mao, and Z. Liu, “Catalpol suppressed proliferation, growth and invasion of CT26 colon cancer by inhibiting inflammation and tumor angiogenesis,” Biomedicine & Pharmacotherapy, vol. 95, pp. 68–76, 2017. View at: Publisher Site | Google Scholar
  144. W. K. Kim, D. H. Bach, H. W. Ryu et al., “Cytotoxic activities of Telectadium dongnaiense and its constituents by inhibition of the Wnt/β-catenin signaling pathway,” Phytomedicine, vol. 34, pp. 136–142, 2017. View at: Publisher Site | Google Scholar
  145. P. Budchart, A. Khamwut, C. Sinthuvanich, S. Ratanapo, Y. Poovorawan, and N. P. T-Thienprasert, “Partially purified Gloriosa superba peptides inhibit colon cancer cell viability by inducing apoptosis through p53 upregulation,” The American Journal of the Medical Sciences, vol. 354, no. 4, pp. 423–429, 2017. View at: Publisher Site | Google Scholar
  146. T. Ranjbarnejad, M. Saidijam, S. Moradkhani, and R. Najafi, “Methanolic extract of Boswellia serrata exhibits anti-cancer activities by targeting microsomal prostaglandin E synthase-1 in human colon cancer cells,” Prostaglandins & Other Lipid Mediators, vol. 131, pp. 1–8, 2017. View at: Publisher Site | Google Scholar
  147. R. Direito, A. Lima, J. Rocha et al., “Dyospiros kaki phenolics inhibit colitis and colon cancer cell proliferation, but not gelatinase activities,” The Journal of Nutritional Biochemistry, vol. 46, pp. 100–108, 2017. View at: Publisher Site | Google Scholar
  148. J. Hafsa, K. M. Hammi, M. R. B. Khedher et al., “Inhibition of protein glycation, antioxidant and antiproliferative activities of Carpobrotus edulis extracts,” Biomedicine & Pharmacotherapy, vol. 84, pp. 1496–1503, 2016. View at: Publisher Site | Google Scholar
  149. N. Campos-Xolalpa, Á. J. Alonso-Castro, E. Sánchez-Mendoza, M. Á. Zavala-Sánchez, and S. Pérez-Gutiérrez, “Cytotoxic activity of the chloroform extract and four diterpenes isolated from Salvia ballotiflora,” Revista Brasileira de Farmacognosia, vol. 27, no. 3, pp. 302–305, 2017. View at: Publisher Site | Google Scholar
  150. N. Sharma, A. Kumar, P. R. Sharma et al., “A new clerodane furano diterpene glycoside from Tinospora cordifolia triggers autophagy and apoptosis in HCT-116 colon cancer cells,” Journal of Ethnopharmacology, vol. 211, pp. 295–310, 2018. View at: Publisher Site | Google Scholar
  151. T. F. F. da Silveira, T. C. L. de Souza, A. V. Carvalho, A. B. Ribeiro, G. G. C. Kuhnle, and H. T. Godoy, “White açaí juice (Euterpe oleracea): phenolic composition by LC-ESI-MS/MS, antioxidant capacity and inhibition effect on the formation of colorectal cancer related compounds,” Journal of Functional Foods, vol. 36, pp. 215–223, 2017. View at: Publisher Site | Google Scholar
  152. S. Li, L. Zhaohuan, Z. Guangshun, X. Guanhua, and Z. Guangji, “Diterpenoid Tanshinones, the extract from Danshen (Radix Salviae Miltiorrhizae) induced apoptosis in nine human cancer cell lines,” Journal of Traditional Chinese Medicine, vol. 36, no. 4, pp. 514–521, 2016. View at: Publisher Site | Google Scholar
  153. K. Gouthamchandra, H. V. Sudeep, B. J. Venkatesh, and K. Shyam Prasad, “Chlorogenic acid complex (CGA7), standardized extract from green coffee beans exerts anticancer effects against cultured human colon cancer HCT-116 cells,” Food Science and Human Wellness, vol. 6, no. 3, pp. 147–153, 2017. View at: Publisher Site | Google Scholar
  154. M. Asif, A. H. S. Yehya, M. A. al-Mansoub et al., “Anticancer attributes of Illicium verum essential oils against colon cancer,” South African Journal of Botany, vol. 103, pp. 156–161, 2016. View at: Publisher Site | Google Scholar
  155. T. Sriyatep, C. Tantapakul, R. J. Andersen et al., “Resolution and identification of scalemic caged xanthones from the leaf extract of Garcinia propinqua having potent cytotoxicities against colon cancer cells,” Fitoterapia, vol. 124, pp. 34–41, 2018. View at: Publisher Site | Google Scholar
  156. T. Sriyatep, R. J. Andersen, B. O. Patrick et al., “Scalemic caged xanthones isolated from the stem bark extract of Garcinia propinqua,” Journal of Natural Products, vol. 80, no. 5, pp. 1658–1667, 2017. View at: Publisher Site | Google Scholar
  157. G. Riccio, M. Maisto, S. Bottone et al., “WNT inhibitory activity of Malus pumila Miller cv Annurca and Malus domestica cv Limoncella apple extracts on human colon-rectal cells carrying familial adenomatous polyposis mutations,” Nutrients, vol. 9, no. 11, p. 1262, 2017. View at: Publisher Site | Google Scholar
  158. E. S. Son, Y. O. Kim, C. G. Park et al., “Coix lacryma-jobi var. ma-yuen Stapf sprout extract has anti-metastatic activity in colon cancer cells in vitro,” BMC Complementary and Alternative Medicine, vol. 17, no. 1, p. 486, 2017. View at: Publisher Site | Google Scholar
  159. M. Asif, A. Shafaei, A. S. Abdul Majid et al., “Mesua ferrea stem bark extract induces apoptosis and inhibits metastasis in human colorectal carcinoma HCT 116 cells, through modulation of multiple cell signalling pathways,” Chinese Journal of Natural Medicines, vol. 15, no. 7, pp. 505–514, 2017. View at: Publisher Site | Google Scholar
  160. H. Zhu, H. Zhao, L. Zhang et al., “Dandelion root extract suppressed gastric cancer cells proliferation and migration through targeting lncRNA-CCAT1,” Biomedicine & Pharmacotherapy, vol. 93, pp. 1010–1017, 2017. View at: Publisher Site | Google Scholar
  161. H. Jin, L. Chen, S. Wang, and D. Chao, “Portulaca oleracea extract can inhibit nodule formation of colon cancer stem cells by regulating gene expression of the Notch signal transduction pathway,” Tumour Biology, vol. 39, no. 7, 2017. View at: Publisher Site | Google Scholar
  162. A. Czerwonka, K. Kawka, K. Cykier, M. K. Lemieszek, and W. Rzeski, “Evaluation of anticancer activity of water and juice extracts of young Hordeum vulgare in human cancer cell lines HT-29 and A549,” Annals of Agricultural and Environmental Medicine : AAEM, vol. 24, no. 2, pp. 345–349, 2017. View at: Publisher Site | Google Scholar
  163. N. Cho, T. T. Ransom, J. Sigmund et al., “Growth inhibition of colon cancer and melanoma cells by versiol derivatives from a Paraconiothyrium species,” Journal of Natural Products, vol. 80, no. 7, pp. 2037–2044, 2017. View at: Publisher Site | Google Scholar
  164. C. Yang, M. Wang, J. Zhou, and Q. Chi, “Bio-synthesis of peppermint leaf extract polyphenols capped nano-platinum and their in-vitro cytotoxicity towards colon cancer cell lines (HCT 116),” Materials Science and Engineering: C, vol. 77, pp. 1012–1016, 2017. View at: Publisher Site | Google Scholar
  165. C. Li, Y. Jeong, and M. Kim, “Mammea longifolia Planch. and Triana fruit extract induces cell death in the human colon cancer cell line, SW480, via mitochondria-related apoptosis and activation of p53,” Journal of Medicinal Food, vol. 20, no. 5, pp. 485–490, 2017. View at: Publisher Site | Google Scholar
  166. A. Manosroi, M. Sainakham, C. Chankhampan, W. Manosroi, and J. Manosroi, “In vitro anti-cancer activities of Job’s tears (Coix lachryma-jobi Linn.) extracts on human colon adenocarcinoma,” Saudi Journal of Biological Sciences, vol. 23, no. 2, pp. 248–256, 2016. View at: Publisher Site | Google Scholar
  167. R. Mata, J. R. Nakkala, and S. R. Sadras, “Polyphenol stabilized colloidal gold nanoparticles from Abutilon indicum leaf extract induce apoptosis in HT-29 colon cancer cells,” Colloids and Surfaces B: Biointerfaces, vol. 143, pp. 499–510, 2016. View at: Publisher Site | Google Scholar
  168. N. H. Yim, M. J. Gu, Y. H. Hwang, W. K. Cho, and J. Y. Ma, “Water extract of Galla Rhois with steaming process enhances apoptotic cell death in human colon cancer cells,” Integrative Medicine Research, vol. 5, no. 4, pp. 284–292, 2016. View at: Publisher Site | Google Scholar
  169. E. J. Kim, G. T. Kim, B. M. Kim, E. G. Lim, S. Y. Kim, and Y. M. Kim, “Apoptosis-induced effects of extract from Artemisia annua Linne by modulating PTEN/p53/PDK1/Akt/ signal pathways through PTEN/p53-independent manner in HCT116 colon cancer cells,” BMC Complementary and Alternative Medicine, vol. 17, no. 1, p. 236, 2017. View at: Publisher Site | Google Scholar
  170. X. Zhao, X. Feng, C. Wang, D. Peng, K. Zhu, and J. L. Song, “Anticancer activity of Nelumbo nucifera stamen extract in human colon cancer HCT-116 cells in vitro,” Oncology Letters, vol. 13, no. 3, pp. 1470–1478, 2017. View at: Publisher Site | Google Scholar
  171. H. Guo, H. Guan, W. Yang et al., “Pro-apoptotic and anti-proliferative effects of corn silk extract on human colon cancer cell lines,” Oncology Letters, vol. 13, no. 2, pp. 973–978, 2017. View at: Publisher Site | Google Scholar
  172. H. J. Hsu, R. F. Huang, T. H. Kao, B. S. Inbaraj, and B. H. Chen, “Preparation of carotenoid extracts and nanoemulsions from Lycium barbarum L. and their effects on growth of HT-29 colon cancer cells,” Nanotechnology, vol. 28, no. 13, article 135103, 2017. View at: Publisher Site | Google Scholar
  173. V. P. Venancio, P. A. Cipriano, H. Kim, L. M. G. Antunes, S. T. Talcott, and S. U. Mertens-Talcott, “Cocoplum (Chrysobalanus icaco L.) anthocyanins exert anti-inflammatory activity in human colon cancer and non-malignant colon cells,” Food & Function, vol. 8, no. 1, pp. 307–314, 2017. View at: Publisher Site | Google Scholar
  174. R. Nozaki, T. Kono, H. Bochimoto et al., “Zanthoxylum fruit extract from Japanese pepper promotes autophagic cell death in cancer cells,” Oncotarget, vol. 7, no. 43, pp. 70437–70446, 2016. View at: Publisher Site | Google Scholar
  175. R. Acquaviva, V. Sorrenti, R. Santangelo et al., “Effects of an extract of Celtis aetnensis (Tornab.) Strobl twigs on human colon cancer cell cultures,” Oncology Reports, vol. 36, no. 4, pp. 2298–2304, 2016. View at: Publisher Site | Google Scholar
  176. S. Jimenez, S. Gascon, A. Luquin, M. Laguna, C. Ancin-Azpilicueta, and M. J. Rodriguez-Yoldi, “Rosa canina extracts have antiproliferative and antioxidant effects on Caco-2 human colon cancer,” PLoS One, vol. 11, no. 7, article e0159136, 2016. View at: Publisher Site | Google Scholar
  177. A. I. Elkady, R. A. Hussein, and S. M. El-Assouli, “Harmal extract induces apoptosis of HCT116 human colon cancer cells, mediated by inhibition of nuclear factor-κB and activator protein-1 signaling pathways and induction of cytoprotective genes,” Asian Pacific Journal of Cancer Prevention : APJCP, vol. 17, no. 4, pp. 1947–1959, 2016. View at: Publisher Site | Google Scholar
  178. M. Amigo-Benavent, S. Wang, R. Mateos, B. Sarria, and L. Bravo, “Antiproliferative and cytotoxic effects of green coffee and yerba mate extracts, their main hydroxycinnamic acids, methylxanthine and metabolites in different human cell lines,” Food and Chemical Toxicology, vol. 106, Part A, pp. 125–138, 2017. View at: Publisher Site | Google Scholar
  179. D. J. de Rodríguez, D. A. Carrillo-Lomelí, N. E. Rocha-Guzmán et al., “Antioxidant, anti-inflammatory and apoptotic effects of Flourensia microphylla on HT-29 colon cancer cells,” Industrial Crops and Products, vol. 107, pp. 472–481, 2017. View at: Publisher Site | Google Scholar
  180. K. Y. Cheah, G. S. Howarth, and S. E. P. Bastian, “Grape seed extract dose-responsively decreases disease severity in a rat model of mucositis; Concomitantly Enhancing Chemotherapeutic Effectiveness in Colon Cancer Cells,” PLoS ONE, vol. 9, no. 1, article e85184, 2014. View at: Publisher Site | Google Scholar
  181. M. M. Derry, K. Raina, R. Agarwal, and C. Agarwal, “Characterization of azoxymethane-induced colon tumor metastasis to lung in a mouse model relevant to human sporadic colorectal cancer and evaluation of grape seed extract efficacy,” Experimental and Toxicologic Pathology, vol. 66, no. 5-6, pp. 235–242, 2014. View at: Publisher Site | Google Scholar
  182. Y. D. Jung, M. S. Kim, B. A. Shin et al., “EGCG, a major component of green tea, inhibits tumour growth by inhibiting VEGF induction in human colon carcinoma cells,” British Journal of Cancer, vol. 84, no. 6, pp. 844–850, 2001. View at: Publisher Site | Google Scholar
  183. M. W. Roomi, V. Ivanov, T. Kalinovsky, A. Niedzwiecki, and M. Rath, “In vivo antitumor effect of ascorbic acid, lysine, proline and green tea extract on human colon cancer cell HCT 116 xenografts in nude mice: evaluation of tumor growth and immunohistochemistry,” Oncology Reports, vol. 13, no. 3, pp. 421–425, 2005. View at: Google Scholar
  184. Y. Z. H.-Y. Hashim, J. Worthington, P. Allsopp et al., “Virgin olive oil phenolics extract inhibit invasion of HT115 human colon cancer cells in vitro and in vivo,” Food & Function, vol. 5, no. 7, pp. 1513–1519, 2014. View at: Publisher Site | Google Scholar
  185. C. C. Tseng, H. F. Shang, L. F. Wang et al., “Antitumor and immunostimulating effects of Anoectochilus formosanus Hayata,” Phytomedicine, vol. 13, no. 5, pp. 366–370, 2006. View at: Publisher Site | Google Scholar
  186. S.-W. Hsuan, C.-C. Chyau, H.-Y. Hung, J.-H. Chen, and F.-P. Chou, “The induction of apoptosis and autophagy by Wasabia japonica extract in colon cancer,” European Journal of Nutrition, vol. 55, no. 2, pp. 491–503, 2016. View at: Publisher Site | Google Scholar
  187. E. Rouhollahi, S. Zorofchian Moghadamtousi, M. Paydar et al., “Inhibitory effect of Curcuma purpurascens BI. rhizome on HT-29 colon cancer cells through mitochondrial-dependent apoptosis pathway,” BMC Complementary and Alternative Medicine, vol. 15, no. 1, p. 15, 2015. View at: Publisher Site | Google Scholar
  188. C. Yu, X.-D. Wen, Z. Zhang et al., “American ginseng attenuates azoxymethane/dextran sodium sulfate-induced colon carcinogenesis in mice,” Journal of Ginseng Research, vol. 39, no. 1, pp. 14–21, 2015. View at: Publisher Site | Google Scholar
  189. S. M. Butler, M. A. Wallig, C. W. Nho et al., “A polyacetylene-rich extract from Gymnaster koraiensis strongly inhibits colitis-associated colon cancer in mice,” Food and Chemical Toxicology, vol. 53, pp. 235–239, 2013. View at: Publisher Site | Google Scholar
  190. P. Arulselvan, C.-C. Wen, C.-W. Lan, Y.-H. Chen, W.-C. Wei, and N.-S. Yang, “Dietary administration of scallion extract effectively inhibits colorectal tumor growth: cellular and molecular mechanisms in mice,” PloS One, vol. 7, no. 9, article e44658, 2012. View at: Publisher Site | Google Scholar
  191. D. S. Wang, G. H. Rizwani, H. Guo et al., “Annona squamosa Linn: cytotoxic activity found in leaf extract against human tumor cell lines,” Pakistan Journal of Pharmaceutical Sciences, vol. 27, no. 5, pp. 1559–1563, 2014. View at: Google Scholar
  192. K.-W. Park, J. Kundu, I. G. Chae, S. C. Bachar, J.-W. Bae, and K.-S. Chun, “Methanol Extract of Flacourtia indica Aerial Parts Induces Apoptosis via Generation of ROS and Activation of Caspases in Human Colon Cancer HCT116 Cells,” Asian Pacific Journal of Cancer Prevention, vol. 15, no. 17, pp. 7291–7296, 2014. View at: Publisher Site | Google Scholar
  193. A. Thyagarajan, A. Jedinak, H. Nguyen et al., “Triterpenes from Ganoderma lucidum induce autophagy in colon cancer through the inhibition of p38 mitogen-activated kinase (p38 MAPK),” Nutrition and Cancer, vol. 62, no. 5, pp. 630–640, 2010. View at: Publisher Site | Google Scholar
  194. C. Huang, Y. Huang, J. Li et al., “Inhibition of benzo(a)pyrene diol-epoxide-induced transactivation of activated protein 1 and nuclear factor κB by black raspberry extracts,” Cancer Research, vol. 62, no. 23, pp. 6857–6863, 2002. View at: Google Scholar
  195. B. Bassani, T. Rossi, D. de Stefano et al., “Potential chemopreventive activities of a polyphenol rich purified extract from olive mill wastewater on colon cancer cells,” Journal of Functional Foods, vol. 27, pp. 236–248, 2016. View at: Publisher Site | Google Scholar
  196. W. Zeriouh, A. Nani, M. Belarbi et al., “Phenolic extract from oleaster (Olea europaea var. Sylvestris) leaves reduces colon cancer growth and induces caspase-dependent apoptosis in colon cancer cells via the mitochondrial apoptotic pathway,” PloS One, vol. 12, no. 2, article e0170823, 2017. View at: Publisher Site | Google Scholar
  197. H. H. Ahmed, H. S. El-Abhar, E. A. K. Hassanin, N. F. Abdelkader, and M. B. Shalaby, “Ginkgo biloba L. leaf extract offers multiple mechanisms in bridling N-methylnitrosourea - mediated experimental colorectal cancer,” Biomedicine & Pharmacotherapy, vol. 95, pp. 387–393, 2017. View at: Publisher Site | Google Scholar
  198. B. Subramaniyan, N. Polachi, and G. Mathan, “Isocoreopsin: an active constituent of n-butanol extract of Butea monosperma flowers against colorectal cancer (CRC),” Journal of Pharmaceutical Analysis, vol. 6, no. 5, pp. 318–325, 2016. View at: Publisher Site | Google Scholar
  199. P. Ovadje, S. Ammar, J. A. Guerrero, J. T. Arnason, and S. Pandey, “Dandelion root extract affects colorectal cancer proliferation and survival through the activation of multiple death signalling pathways,” Oncotarget, vol. 7, no. 45, pp. 73080–73100, 2016. View at: Publisher Site | Google Scholar
  200. S. Tanaka, K. Haruma, M. Yoshihara et al., “Aged garlic extract has potential suppressive effect on colorectal adenomas in humans,” The Journal of Nutrition, vol. 136, no. 3, pp. 821S–826S, 2006. View at: Publisher Site | Google Scholar
  201. A. di Francesco, A. Falconi, C. di Germanio et al., “Extravirgin olive oil up-regulates CB1 tumor suppressor gene in human colon cancer cells and in rat colon via epigenetic mechanisms,” The Journal of Nutritional Biochemistry, vol. 26, no. 3, pp. 250–258, 2015. View at: Publisher Site | Google Scholar
  202. T. Srihari, M. Sengottuvelan, and N. Nalini, “Dose-dependent effect of oregano (Origanum vulgare L.) on lipid peroxidation and antioxidant status in 1,2-dimethylhydrazine-induced rat colon carcinogenesis,” The Journal of Pharmacy and Pharmacology, vol. 60, no. 6, pp. 787–794, 2008. View at: Publisher Site | Google Scholar
  203. A. Caimari, F. Puiggròs, M. Suárez et al., “The intake of a hazelnut skin extract improves the plasma lipid profile and reduces the lithocholic/deoxycholic bile acid faecal ratio, a risk factor for colon cancer, in hamsters fed a high-fat diet,” Food Chemistry, vol. 167, pp. 138–144, 2015. View at: Publisher Site | Google Scholar
  204. L. Pan, F. Will, N. Frank, H. Dietrich, H. Bartsch, and C. Gerhauser, “Natural cloudy apple juice and polyphenol-enriched apple juice extract prevent intestinal adenoma formation in the APCMin/+ model for colon cancer prevention,” European Journal of Cancer Supplements, vol. 4, no. 1, pp. 55-56, 2006. View at: Publisher Site | Google Scholar
  205. R. Acquaviva, L. Iauk, V. Sorrenti et al., “Oxidative profile in patients with colon cancer: effects of Ruta chalepensis L,” European Review for Medical and Pharmacological Sciences, vol. 15, no. 2, pp. 181–191, 2011. View at: Google Scholar
  206. N. A. de Moura, B. F. Caetano, K. Sivieri et al., “Characterization of potentially chemopreventive phenols in extracts of brown rice that inhibit the growth of human breast and colon cancer cells,” Food and Chemical Toxicology, vol. 50, no. 8, pp. 2902–2910, 2012. View at: Publisher Site | Google Scholar
  207. H. H. Ahmed, H. S. El-Abhar, E. A. K. Hassanin, N. F. Abdelkader, and M. B. Shalaby, “Punica granatum suppresses colon cancer through downregulation of Wnt/β-catenin in rat model,” Revista Brasileira de Farmacognosia, vol. 27, no. 5, pp. 627–635, 2017. View at: Publisher Site | Google Scholar
  208. N. R. Shah and B. M. Patel, “Secoisolariciresinol diglucoside rich extract of L. usitatissimum prevents diabetic colon cancer through inhibition of CDK4,” Biomedicine & Pharmacotherapy, vol. 83, pp. 733–739, 2016. View at: Publisher Site | Google Scholar
  209. N. L. Md Nasir, N. E. Kamsani, N. Mohtarrudin, F. Othman, S. F. Md Tohid, and Z. A. Zakaria, “Anticarcinogenic activity of Muntingia calabura leaves methanol extract against the azoxymethane-induced colon cancer in rats involved modulation of the colonic antioxidant system partly by flavonoids,” Pharmaceutical Biology, vol. 55, no. 1, pp. 2102–2109, 2016. View at: Publisher Site | Google Scholar
  210. S. A. Im, J. W. Kim, H. S. Kim et al., “Prevention of azoxymethane/dextran sodium sulfate-induced mouse colon carcinogenesis by processed Aloe vera gel,” International Immunopharmacology, vol. 40, pp. 428–435, 2016. View at: Publisher Site | Google Scholar
  211. F. Yao, J. Y. Zhang, X. Xiao, Y. Dong, and X. H. Zhou, “Antitumor activities and apoptosis-regulated mechanisms of fermented barley extract in the transplantation tumor model of human HT-29 cells in nude mice,” Biomedical and Environmental Sciences, vol. 30, no. 1, pp. 10–21, 2017. View at: Publisher Site | Google Scholar
  212. A. T. Endharti, A. Wulandari, A. Listyana, E. Norahmawati, and S. Permana, “Dendrophthoe pentandra (L.) Miq extract effectively inhibits inflammation, proliferation and induces p53 expression on colitis-associated colon cancer,” BMC Complementary and Alternative Medicine, vol. 16, no. 1, p. 374, 2016. View at: Publisher Site | Google Scholar
  213. S. S. Dahham, L. E. A. Hassan, M. B. K. Ahamed, A. S. A. Majid, A. M. S. A. Majid, and N. N. Zulkepli, “In vivo toxicity and antitumor activity of essential oils extract from agarwood (Aquilaria crassna),” BMC Complementary and Alternative Medicine, vol. 16, no. 1, p. 236, 2016. View at: Publisher Site | Google Scholar
  214. M. R. Malayeri, A. Dadkhah, F. Fatemi et al., “Chemotherapeutic effect of Berberis integerrima hydroalcoholic extract on colon cancer development in the 1,2-dimethyl hydrazine rat model,” Zeitschrift für Naturforschung C, vol. 71, no. 7-8, pp. 225–232, 2016. View at: Publisher Site | Google Scholar
  215. A. Bounaama, S. Enayat, M. S. Ceyhan, H. Moulahoum, B. Djerdjouri, and S. Banerjee, “Ethanolic extract of bark from Salix aegyptiaca ameliorates 1,2-dimethylhydrazine-induced colon carcinogenesis in mice by reducing oxidative stress,” Nutrition and Cancer, vol. 68, no. 3, pp. 495–506, 2016. View at: Publisher Site | Google Scholar
  216. Q. Zhu, J. Meisinger, D. H. V. Thiel, Y. Zhang, and S. Mobarhan, “Effects of soybean extract on morphology and survival of Caco-2, SW620, and HT-29 cells,” Nutrition and Cancer, vol. 42, no. 1, pp. 131–140, 2002. View at: Publisher Site | Google Scholar
  217. M. E. Juan, U. Wenzel, V. Ruiz-Gutierrez, H. Daniel, and J. M. Planas, “Olive fruit extracts inhibit proliferation and induce apoptosis in HT-29 human colon cancer cells,” The Journal of Nutrition, vol. 136, no. 10, pp. 2553–2557, 2006. View at: Publisher Site | Google Scholar

Copyright © 2019 Paola Aiello et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


More related articles

 PDF Download Citation Citation
 Download other formatsMore
 Order printed copiesOrder
Views30018
Downloads3170
Citations

Related articles

Article of the Year Award: Outstanding research contributions of 2020, as selected by our Chief Editors. Read the winning articles.