Medicinal Plants in the Prevention and Treatment of Colon Cancer

Table 1

Cytotoxic effects of medicinal plants on colon cancer in in vitro models.

Scientific name	Parts used	Cell line	Conc.	Type of extract	Important compounds	Cellular effect	Mechanisms	References
Vitis vinifera	Fruit	HCT116	NM	Lyophilized	Hydroxycinnamic acids, proanthocyanidins, stilbenoids	Increase 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]
	Fruit	Caco-2	365 mg/g	Methanolic	Catechin, epicatechin, quercetin, gallic acid	Antiproliferative activity and direct initiation of cell death	Blockage in the G2/M phase	[28, 29]
	Seed	Caco-2	10–25 μg/mL	Aqueous	Procyanidins	(i) Increased crypt depth; (ii) Inhibited cell viability and decreased histological damage score	Reduced MPO (myeloperoxidase) activity	[29]
	Skin	NM	7.5, 30, 60 μg/mL	Methanolic	4-Geranyloxyferulic acid	NM	NM	[30]
	Seed	Colon cancer stem cells	6.25, 12.5, 25 μg/mL	NM	(+)-catechin, (−)-epicatechin	NM	(i) Increment of p53, Bax/Bcl-2 ratio, and cleaved PARP; (ii) Inhibition of Wnt/β-catenin signaling	[31]
Allium sativum	Root	HT-29	20, 50, 100 mg/mL	Ethanolic	NM	Induction 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 max	Seed	Caco-2, SW620, HT-29	12.5 μg/mL	Aqueous	Anthoxanthin	Cell death and significant reduction of cell density	Enhancement of Rab6 protein levels	[33]
	Seed	HT-29	240, 600 ppm	Crude	Saponin		Suppression of PKC activation and increase of alkaline phosphatase activity	[33]
	Seed	HT-29	NM	Crude	Saponin	NM	(i) Suppression of the degradation of IκBα in PMA-stimulated cells; (ii) Downregulation of COX-2 and PKC expressions	[34]
Camellia sinensis	Leaf	HT-29	0, 10, 30, 50 μM	Aqueous	Catechin, epigallocatechin gallate	1.9-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]
	Leaf	Caco-2, HT-29	300 μM	Aqueous	Theaflavins (TF-2T, F-3, TF-1)	Human colon cancer cell apoptosis induction	Modulation of NFκB, AP-1, CREB, and/or IL-6	[36]
	Leaf	HT-29	68-80; 0.73 μg/mL	Hot water extract	Flavan-3-ol (catechin & tannin) & polyphenols (teadenol B)	Inhibition of proliferation of HT-29 cells	Increased expression levels of caspases 3/7, 8, and 9	[35]
Olea europaea	Fruit	HT-29	150, 55.5; 200 and 74 μmol/L	Methanolic and chloroform	Maslinic acid, oleanolic acid	Antiproliferative activity	(i) Increased caspase 3-like activity to 6-fold; (ii) Production of superoxide anions in the mitochondria	[37]
	Fruit, leaf	SW480 and HT-29	100–400 m/z	Methanolic & hexane	Oleic acid, linoleic acid, gamma-linolenic acid, lignans, flavonoids, secoiridoids	Reduced 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]
	Fruit	Caco-2	50 μM	Aqueous	Phenolic compounds, authentic hydroxyl tyrosol (HT)	Reduced proliferation of Caco-2 cells	Reduction of the methylation levels of CNR1 promoter	[39]
	Fruit	HT115	25 μg/mL	Hydroethanolic	Phenolic compounds (p-hydroxyphenyl ethanol, pinoresinol & dihydroxyphenyl ethanol)	NM	Inhibition by reduced expression of a range of α5 & β1	[40]
	Olive mill wastewater	HT-29, HCT116, CT26	NM	Methanolic	Hydroxytyrosol	(i) Inhibited proliferation; (ii) Inhibited migration and invasion	(i) Reduced sprout formation; (ii) Inhibited VEGF and IL-8 levels	[41]
	Fruit	Caco-2	0-2,000 μg/mL	Ethanolic	Tyrosol, hydroxytyrosol, oleuropein, rutin, quercetin and glucoside forms of luteolin and apigenin	NM	(i) Induction of the cell cycle arrest in S-phase	[42]
Punica granatum	Juice	HT-29	50 mg/L	Aqueous	Ellagitannins, punicalagin	Inhibition 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]
	Seed	LS174	63.2 μg/mL	Supercritical fluid	Punicic acid, γ-tocopherol, α-tocopherol	Cytotoxic activity	(i) Slightly decreased development of tubules from elongated cell bodies; (ii) Reduction of the number of cell connections	[44]
Glycyrrhiza glabra	Root	HT-29	12.2 and 31 μg/mL	Ethanolic	Licochalcone	NM	Increase of the protein levels of proapoptotic Bax	[37]
Opuntia ficus-indica	Fruit	Caco-2	115 μM	Aqueous	Betalain pigment indicaxanthin	Apoptosis of proliferating cells	(i) Demethylation of the tumor suppressor p16INK4a gene promoter; (ii) Reactivation of the silenced mRNA expression and accumulation of p16INK4a	[38]
	Fruit	HT-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 NaOH	Isorhamnetin glycosides (IG5 and IG6)-phenol	Cell death through apoptosis and necrosis	Increased activity of caspase 3/7	[45]
Piper betle	Leaf	HT-29 and HCT116	200.0 μg/mL	Aqueous	Hydroxychavicol	Antioxidant capacity and induction of a greater apoptotic effect	(i) Scavenging activity; (ii) Formation of electrophilic metabolites	[41, 46]
Fragaria×ananassa	Fruit	HT-29	0.025, 0.05, 0.25, 0.5%	Ethanolic	Ascorbate, ellagic acid	Decreased proliferation of HT-29 cells	Increase in the levels of 8OHA and decrease in the levels of 8OHG	[40]
Sasa quelpaertensis	Leaf	HT-29 HCT116	0, 100, 200, 300 mg/L	Ethanolic	p-Coumaric acid, tricin	Inhibited colony formation	Nonadherent sphere formation suppressed CD133+ & CD44+ population	[41]
Salvia chinensis	Stem	HCT116, COLO 205	10, 20, 40,60, 80, 100 mg/L	Polyphenolic	Terpenoids, phenolic acid, flavonoids, dibenzylcyclooctadiene	Apoptosis & loss of mitochondrial membrane	Induced G0/G1 cell cycle	[42]
Rubus idaeus L.	Fruit	HT-29, HT-115, Caco-2	3.125, 6.25, 12.5, 25, 50 mg/L	Acetate	Polyphenol, anthocyanin, ellagitannin	NM	Decreased population of cells in G1 phase	[47]
		LoVo	50 μL	Aqueous	NM	Inhibited proliferation of LoVo	Suppression of the NFκB pathway	[48]
Curcuma longa	Root	HT-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	Ethanolic	Curcumin (diferuloylmethane)	Inhibited formation of HCT116 spheroids	NM	[49]
Eleutherococcus senticosus	Root	HCT116	12.5, 25, 50, 100	Methanolic	Eleutherosides, triterpenoid saponins, glycans	NM	Activation of natural killer cells and thus enhancement of immune function	[50]
Tabernaemontana divaricata L.	Leaf	HT-29, HCT15	10, 30, 100 mg/L	Ethyl acetate, chloroform, methanolic	Alkaloids	NM	Inhibited the unwinding of supercoiled DNA	[45]
Millingtonia hortensis	Root, flower, leaf	RKO	50, 100, 200, 400, 800 mg/L	Aqueous	Phenylethanoid glycoside, squalene, salidroside, 2-phenyl rutinoside	Apoptosis induction	(i) Increase of fragmented DNA; (ii) Decrease of the expression of antiapoptotic proteins, Bcl-xL and p-BAD	[46]
	Powder	RKO	200, 400, 800 μg/mL	Aqueous	Water soluble compounds	Antiproliferative effect	NM	[51]
Thai purple rice	Seed	Caco-2, Cat. No. HTB-37	16.11 μg/mL	Methanol acidified	Cyanidin-3-glucoside and peonidin-3-glucoside, anthocyanins, phenolic compounds	(i) Antioxidation of anthocyanins and phenols; (ii) Antiproliferation of colon cancer cells	NM	[52]
Annona muricata	Leaf	HCT116, HT-29	and	Ethanolic	Alkaloids, acetogenins, essential oils	Block 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]
	NM	HT-29, HCT116	<4, <20 μg/mL	EtOAc	Annopentocin A, annopentocin B, annopentocin C, cis- and trans-annomuricin-D-ones, annomuricin E	NM	Suppression of ATP production and NADH oxidase in cancer cells	[54]
Pistacia lentiscus L. var. chia	Leaf	HCT116	NM	Ethanolic	Resin, 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]
	Resin	HCT116	100 μg/mL	Hexane	Caryophyllene	Induction 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 constituents	HCT116	0-2.0 mg/mL	Aqueous	Ginseng (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 potatoes	Fruit	Colon cancer stem cells	5.0 μg/mL	Ethanol, methanol, ethyl acetate	Anthocyanin, β-catenin, cytochrome c	Critical 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 vulgaris	Leaf	HT-29	NM	Ethanolic	Polysaccharides, oligosaccharides	Changes 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.	Fruit	HT-29	, , ()	Hydroalcoholic	Betacyanins, flavonoids (isorhamnetin derivatives) and phenolic acids (ferulic acid)	NM	Induced cell cycle arrest at different checkpoints—G1, G2/M, and S	[60]
Suillus luteus	NM	HCT15	400 μg/mL	Methanolic	Protocatechuic 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 trifoliata	Leaf	HT-29	0.63 μM	Aqueous (in acetone)	β-Sitosterol, 2-hydroxy-1,2,3-propanetricarboxylic acid 2-methyl ester	Arrest of cell growth was observed with β-sitosterol	NM	[62]
Rosmarinus officinalis L.	Leaf	SW 620, DLD-1	0-120 μg/mL	Methanolic	Polyphenols	Antiproliferative effect of 5-FU	Downregulation of TYMS and TK1, enzymes related to 5-FU resistance	[63]
	Leaf	HT-29	SC-RE 30 μg/mL and CA 12.5 μg/mL	Ethanolic	Polyphenols (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]
	NM	HT-29	10, 20, 30, 40, 50, 60, 70 μg/mL	NM	Carnosic acid, carnosol, rosmarinic acid, rosmanol	NM	NM	[65]
	Leaf	HGUE-C-1, HT-29, and SW480	20–40 mg/mL	CO2-supercritical fluid extract	Carnosic acid, carnosol, and betulinic acid	NM	(i) Prooxidative capability by increasing the intracellular generation of ROS; (ii) Activation of Nrf2	[66]
Glehnia littoralis	Leaf	HT-29	50 mg/mL	Methanolic	Bergapten, isoimpinellin, xanthotoxin, imperatorin, panaxydiol, falcarindiol, falcarinol	Induced 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 officinalis	Leaf	HCT116	20 mg/mL	Aqueous	Phenylethanoid 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 spicata	Leaf	RCM-1	12.5 μg/mL	N-Hexane	Acetic acid 3-methylthio propyl ester (AMTP), methyl thio propionic acid ethyl ester (MTPE)	Exhibited antimutagenic activity	Auraptene (7-geranyloxycoumarin) having a monoterpene moiety and β-cryptoxanthin (one of the tetraterpenes) increased antibody production	[69]
Euphoria longana Lam.	Seed	SW 480	0–100 μg/mL	Ethanolic	Corilagin, 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 frutescens	Flower	Caco-2	1/50 dilution of the ethanolic extract	Ethanolic	Amino acids, including L-arginine and L-canavanine, pinitol, flavonoids, and triterpenoid saponins as well as hexadecanoic acid and γ-sitosterol	Disruption of the key molecules in the PI3K pathway thereby inducing apoptosis	Decrease in cell viability and increment in pyknosis as well as loss in cellular membrane integrity	[71]
Melissa officinalis	Leaf	HT-29, T84	346, 120 μg/mL	Ethanolic	Phenolic 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 cristaefolium	Leaf	HT-29	500 mg/mL	Ethanolic	Fucoidans	(i) Reduction of free radicals; (ii) DPPH radical scavenging	Accumulation of cells in G0/G1 phase	[73]
Hedyotis diffusa	NM	HT-29	400 mg/mL	Ethanolic and then DMSO	Octadecyl (E)-p-coumarate, P-E-methoxy-cinnamic acid, ferulic acid, scopoletin, succinic acid, aurantiamide acetate, rubiadin	Suppress 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 Roscoe	Peel	LoVo	100 mg/mL	Ethanolic	Linoleic acid methyl ester, α-zingiberene, and zingiberone	Interesting antiproliferative activity against colorectal carcinoma	NM	[75]
Scutellaria barbata	Leaf	LoVo	413.3 mg/L	Methanolic	Scutellarein, scutellarin, carthamidin, isocarthamidin, wogonin	Induce cell death in the human colon cancer cell line	Increase in the sub-G1 phase and inhibition of cell growth	[76]
Pistacia atlantica, Pistacia lentiscus	Resin	HCT116	100 μg/mL	Hexane extract	Caryophyllene	Induce 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 reticulata	Peel	SNU-C4	100 μg/mL	Methanolic	Limonene, geranial, neral, geranyl acetate, geraniol, β-caryophyllene, nerol, neryl acetate	Induce the apoptosis on SNU-C4, human colon cancer cells	Expression of proapoptotic gene, Bax, and major apoptotic gene, caspase 3	[77]
Echinacea pallida, Echinacea angustifolia, Echinacea purpurea	Root	COLO320	150 mg/mL	Hexanic	Caffeic acid derivatives, alkylamides, polyacetylenes, polysaccharides	Induce apoptosis and promote nuclear DNA fragmentation	(i) Induce apoptosis by increasing caspase 3/7 activity; (ii) Promote nuclear DNA fragmentation	[78]
Nasturtium officinale	Leaf	HT-29	50 μL/mL	Methanolic	Phenethyl 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]
Polysiphonia	NM	SW480, HCT15, HCT116, DLD-1	20 and 40 μg/mL	Methanolic	2,5-Dibromo-3,4-dihydroxybenzyl n-propyl ether	Potentially 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.	Stem	HT-29	200 μg/mL	Methanolic	Aristolochic acid, nitrophenanthrene carboxylic acids	Inhibition 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]
Myrtaceae	Leaf	HCT116	100 μg/mL (in vitro), 200 and 100 μg/disc (in vivo)	Methanolic	Phenols, flavonoid, betulinic acid	Strong 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 prunellae	Leaf	HT-29	200 mg/mL (in vitro), 600 mg/mL (in vivo)	Ethanolic	Rosmarinic acid	Inhibits 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 americana	Root	HCT116	3200 μg/mL	Ethanolic	Jaligonic acids, kaempferol, quercetin, quercetin 3-glucoside, isoquercitrin, ferulic acid	Control of growth and spread of cancer cells	Reduction in the expressions of MYC, PLAU, and TEK	[84]
Morus alba	Leaf	HCT15	13.8 μg/mL	Methanolic	Epicatechin, myricetin, quercetin hydrate, luteolin, kaempferol, ascorbic acid, gallic acid, pelargonidine, p-coumaric acid	Cytotoxic 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 imbricata	Leaf	HT-29	200 μg/mL	Acetone and methanolic	Phenols, 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. radix	HCT116	20 mg/mL	Ethanolic	Asarinin and xanthoxylol	Inhibition of the growth of HCT116 cells	(i) Caspase-dependent apoptosis; (ii) Regulation of p53 expression at transcription level	[87]
Podocarpus elatus	Fruit	HT-29	500 mg/mL	Methanolic	Phenolic and anthocyanin	Reduction 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 purpurea	Flower	Caco-2, HCT116	0–2,000 mg/mL	Hydroethanolic	Cichoric 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]
	Root	COLO320	150 mg/mL	Hexanic	Caffeic acid derivatives, alkylamides, polyacetylenes, polysaccharides	Induce 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 artemisioides	Leaf	NM	100 mg/kg b.w./day	Aqueous	Coumarin, lignans, quinones	30% reduction of tumor-induced neovascularization	NM	[90]
	NM	Caco-2	NM	Ethanolic	Phenolic compounds, flavonoid, diterpenes	Digestive, gastroprotective, antiseptic, anti-inflammatory, and antiproliferative activity	NM	[91]
	Fruit	NL-17	0, 50, 100, 150 μg/mL	Methanolic	α-Mangostin (xanthone)	NM	(i) Induction of caspase 3 and caspase 9 activation; (ii) Induced cell cycle arrest at G1/G0 phase	[92]
	Stem, bark	HT-29	50 μg/mL	Chloroform-soluble	β-Mangostin, garcinone D, cratoxyxanthone	Cytotoxic activity against HT-29 human colon cancer	Inhibition of p50 and p65 activation	[93]
Annona squamosa Linn	Leaf	HCT116	8.98 μg/mL	Crude, Aq ethyl acetate	Acetogenins (annoreticuin & isoannoreticuin) and alkaloids dopamine, salsolinol, and coclaurine	Inhibition 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 scandens	Stem	HT-29	5-15 μg/mL	Ethanolic	Benzyls 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 cannabinum	Aerial parts	HT-29	25 μg/mL	Ethanolic	Pyrrolizidine 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 bicolor	The dermal layer of stalk	HCT116 & colon cancer stem cells	>16 and 103 μg/mL	Phenolic-rich ethanolic, acetone	Apigeninidin & luteolinidin	Antiproliferative	Target p53-dependent and p53-independent pathways	[97]
	Dermal and seed head	CCSC	NM	Methanolic	Apigeninidin, luteolinidin, malvidin 3-O-glucoside, apigenin, luteolin, naringenin, naringenin 7-O-glucoside, eriodictyol 5-glucoside, taxifolin, catechins	NM	(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 cannabinus	Seed	HCT116	KSE (15.625 μg/mL to 1,000 μg/mL)	Ethanolic	Gallic acid, p-hydroxybenzoic acid, caffeic acid, vanillic acid, syringic acid, and p-coumaric and ferulic acids	Cytotoxic activity against human colon cancer HCT116 cells	Apoptosis via blockade of mid G1-late G1-S transition thereby causing G1 phase cell cycle arrest	[99]
Salix aegyptiaca L.	Bark	HCT116 & HT-29	300 μg/mL	Ethanolic	Catechin, salicin, catechol and smaller amounts of gallic acid, epigallocatechin gallate (EGCG), quercetin, coumaric acid, rutin, syringic acid, and vanillin	Anticarcinogenic effects in colon cancer cells	Apoptosis via inhibition of phosphatidylinositol 3-kinase/protein kinase B and mitogen-activated protein kinase signaling pathways	[100]
Rubus coreanum	Fruit	HT-29	400 μg/mL	Aqueous	Polyphenols, gallic acid, sanguine	Induction of apoptosis	(i) Induced activity of caspases 3, 7, and 9; (ii) Cleavage of poly(adenosine diphosphate-ribose) polymerase	[101]
Codonopsis lanceolata	Root	HT-29	200 μg/mL	N-Butanol fraction	Tannins, saponins, polyphenolics, alkaloids	Apoptosis 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 sinensis	Thorn	HCT116	800 μg/mL	Aqueous	Flavonoid, 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]
	Thorn	HCT116	600 μg/mL	Ethanolic	NM	Inhibitory 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 lucidum	Fruit	DLD-1	50 μg/mL	Aqueous	Oleanolic acid, ursolic acid	Inhibited proliferation	(i) Reduction of Tbx3 rescued the dysregulated P14ARF-P53 signaling	[94]
Zingiber officinale	Rhizome	HCT116	5 μM	Ethanolic	6-Paradol, 6- and 10-dehydrogingerdione, 6- and 10-gingerdione, 4-, 6-, 8-, and 10-gingerdiol, 6-methylgingerdiol, zingerone, 6-hydroxyshogaol, 6-, 8-, 10-dehydroshogaol, diarylheptanoids	Inhibitory effects on the proliferation of human colon cancer cells	(i) Arrest at G0/G1 phase; (ii) Reduced DNA synthesis	[103]
Grifola frondosa	Fruit	HT-29	10 ng/mL	Aqueous	Phenolic compounds (pyrogallol, caffeic acid, myricetin, protocatechuic acid)	Inhibition of TNBS-induced rat colitis	Induced cell cycle progression in G0/G1 phase	[104]
Cucumaria frondosa	The enzymatically hydrolyzed epithelium of the edible	HCT116	<150 μg/mL	Hydroalcoholic	Monosulphated triterpenoid glycoside frondoside A, the disulphated glycoside frondoside B, the trisulphated glycoside frondoside C	Inhibition 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 fruticosa	Leaf & twigs	HT-29	10 and 5 mg/kg/day	Methanolic	Sesquiterpene lactone (13-acetoxyrolandrolide)	Antiproliferative effect against human colon cancer cells	Inhibition of the NFκB pathway, NFκB subunit p65 (RelA), upstream mediators IKKβ and oncogenic K-ras	[106]
Cydonia oblonga Miller	Leaf & Fruit	Caco-2	250–500 μg/mL	Methanolic	Phenolic 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 esculenta	Fruits	HT-29	820 mg/mL	Methylene chloride	Steroids (mainly ergosterol derivatives) & polysaccharides & galactomannan	Antioxidant activity in HT-29 colon cancer cells	Inhibition of NF-B activation in the NF-B assay	[108]
Sedum kamtschaticum	Aerial part	HT-29	0–0.5 mg/mL	Methanolic	Buddlejasaponin IV	Induced apoptosis in HT-29 human colon cancer cells	Induction of apoptosis via mitochondrial pathway by downregulation of Bcl-2 protein levels, caspase 3 activation, and subsequent PARP cleavage	[109]
Ginseng and Glycyrrhiza glabra	Leaf	HT-29	500 μL	Aqueous	Uracil, adenine, adenosine, Li-glycyrrhetinic acid, quiritin	NM	Antiproliferative 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 japonicus	Leaf & stem	HT-29	2 mg/mL	Aqueous	Flavonoids, triterpenoids, 4-hydroxybenzoic acid, 3,4-dihydroxybenzoic acid, polysaccharide	Antiproliferation in HT-29 colon cancer cells	Inhibited proliferation at G2 point of the cell cycle and apoptosis via tumor suppressor protein p53	[111]
Ginkgo biloba	Fruit & leaf	HT-29	20–320mg/L	Aqueous	Terpene 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 sativa	Seed	HT-29, SW 480, HCEC	100 μg/mL	Ethyl acetate	Phenolic 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 Makino	Root	HT-29	305.024/mL	Ethanolic	Osthole, auraptenol, imperatorin	Inhibited 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 Makino	Root	HT-29	0.1-5 mg/mL	Aqueous	N-(3-(Aminomethyl)benzyl)acetamidine	Inhibited 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)	Fruit	HT-29 and HCT116	0.10 mg/mL	Ethanolic	Piperidine 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 aspera	Root	COLO 205	50-100 and 150-200 μg/mL	Ethanolic (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 vulgaris	Leaf	HCT116	0.2, 0.4, 0.6, 0.8 mg/mL		Carvacrol and thymol	Inhibited proliferation, adhesion, migration, and invasion of cancer cells		[118]
Dictyopteris undulata	NM	SW480	40 μg/mL	Ethanolic	Cyclozonarone benzoquinone	NM	Induced 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 microspermae	NM	HCT116	0.25, 0.5, 1.0 mg/mL	Methanolic	NM	NM	Upregulation of Bax and caspases 9 and 3 and downregulation of Bcl-2 expression of genes	[120]
Cannabis sativa	Dry flower & leaf	DLD-1 and HCT116	0.3–5 μM	Methanolic	Cannabidiol, phytocannabinoids	Reduced 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.	Fruit	Caco-2	0.2 mg/mL	Aqueous	Phenolic acids (gallic, protocatechuic, hydroxybenzoic, vanillic, isovanillic, syringic, caffeic, ferulic, sinapic, p-coumaric, isoferulic), flavonoid glycosides (quercetin, luteolin, apigenin, and kaempferol), and anthocyanidins	Increasing beneficial bacterial growth and inhibition of proliferation of colon cancer cells	NM	[122]
Melia toosendan	Fruit	SW480, CT26	0, 10, 20, 30, 40, 50 μg/mL	Ethanolic	Triterpenoids, flavonoids, polysaccharide, limonoids	NM	(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.	Flower	HCT116	0.25, 0.5, 1, 2, 4 μg/mL	Ethanolic	Carotenoid, pigment, crocin, crocetin	Induced 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 leaf	Caco-2	0.42 mg/mL	NM	Polyphenols, glycosides of kaempferol, luteolin, and quercetin	Proliferation of Caco-2 cells was greatly inhibited	NM	[125]
Luffa echinata	Fruit	HT-29	50, 100, and 200 μg/mL	Methanolic	Amariin, echinatin, saponins, hentriacontane, gypsogenin, cucurbitacin B, datiscacin, 2-O-β-D-glucopyranosyl cucurbitacin B, and 2-O-β-D-glucopyranosyl cucurbitacin S	Increase 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 hybrid	Fruits (wine)	CCD-18Co	25, 50, 100 μg/mL	NM	Polyphenolics	NM	(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 aethiopica	Dried fruit	HCT116	0, 5, 10, 15, 20, 25, 30 μg/mL	Ethanolic	Ent-15-oxokaur-16-en-19-oic acid (EOKA)	NM	(i) Induced DNA damage, cell cycle arrest in G1 phase, and apoptotic cell death	[128]
Sorghum	Grain	ER-β; nonmalignant young adult mouse colonocytes	1, 5, 10, 100 μg/mL	Aqueous	Flavones (luteolin and apigenin), 3-deoxyanthocyanins naringenin (eriodictyol and naringenin)	Reduced cell growth via apoptosis	Increased caspase 3 activity	[129]
	NM	HT-29, HCT116	0.9-2.0 mg/mL	Hydroethanolic	Procyanidin 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. Chen	Root	LoVo and Caco-2	0, 100, 250, and 500 μg/mL	Alcoholic	Saponin, ginsenoside	NM	Delay in progression of the G0/G1, S, or G2/M cell cycle phases	[131]
Brassica oleracea L. var. italica	Broccoli florets	HCT116	0, 1, 2.5, 5, 10 μg/mL	Ethanolic	Glucoiberin, 3 hydroxy,4(α-L-rhamnopyranosyloxy), benzyl glucosinolate 4-vinyl-3-pyrazolidinone 4-(methyl sulphinyl), butyl thiourea, β-thioglucoside N-hydroxysulphates	NM	NM	[132]
Cistanche deserticola	Dried stem	SW480	In vivo: 0.4 g/kg/day; In vitro: 100 μg/mL	Aqueous	Polysaccharides, 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 japonica	Fruit	Caco-2 and HT-29	10, 25, 50, 75, 100, 125, 150 μM CE	NM	Procyanidins	NM	NM	[134]
Prunus mume	Fruit	SW480, COLO, and WiDr	150, 300, and 600 μg/mL	Hydrophobic	Triterpenoid saponins	NM	(i) Inhibited growth and lysed SW480, COLO, and WiDr; (ii) Induction of massive cytoplasmic vacuoles	[135]
Solanum lyratum	NM	COLO 205	50, 100, 200, 300, 400 μg/mL	EtOH	β-Lycotetraosyl	Induced 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 cynarocephalum	Aerial parts	HCT116, HT-29	0, 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	Aqueous	Flavonoids, lignans, and sesquiterpene lactones	NM	(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 palmifolia	Bulbs	SW480	2.5, 5, 10 μg/mL	MeOH	Eleutherin, isoeleutherin	NM	(i) Inhibited the transcription of TCF/β-catenin; (ii) Decrease in the level of nuclear β-catenin protein	[138]
Asparagus officinalis	Spears	HCT116	76 μg/mL	Acetone	Steroidal 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, pulp	HCCSCs, HCT116	200 μg/mL	Methanolic	Trigonelline, 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 grape	NM	HT-29, HCT116	0.9-2.0 mg/mL	Hydroethanolic	Delphinidin 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 lentil	NM	HT-29, HCT116	0.9-2.0 mg/mL	Hydroethanolic	Delphinidin 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 paraguayense	Leaf	Caco-2, BV-2	0.2, 0.4, 0.6, 0.8, 1.0 mg/mL	Hydroethanolic	Oxalic 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 monosperma	Flower	SW480	200, 370 μg/mL	Floral	n-Butanol	Significant 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 glutinosa	NM	CT26	5, 20, 80 μM	NM	Catalpol	Inhibited 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 dongnaiense	Bark	HCT116	1.5, 2.0 μg/mL	MeOH extract	4-Dicaffeoylquinic acid, quercetin 3-rutinoside, periplocin	NM	(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 superba	Root	SW620	30 ng/mL	Protein hydrolysate extract	Protein hydrolysate	NM	(i) Upregulation of p53; (ii) Downregulation of NFκB	[145]
Boswellia serrata	Resin	HT-29	100, 150 μg	Methanolic	Boswellic acid	Decreased 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 flagelliforme	Leaf	WiDr	70 μg/mL	Ethyl acetate	Glycoside flavonoid, isovitexin, alkaloids	NM	Inhibition of COX-2 expression	[28]
Diospyros kaki	Fruit	HT-29	2,000 μg/mL	Hydroacetone extract	Polyphenol	Impaired cell proliferation and invasion	NM	[147]
Carpobrotus edulis	Leaf	HCT116	1,000 mg/mL	Hydroethanolic	Gallic acid, quercetin, sinapic acid, ferulic acid, luteolin 7-o-glucoside, hyperoside, isoquercitrin, ellagic acid, isorhamnetin 3-O-rutinoside	Inhibited 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 methysticum	Root	HT-29	10, 20, 30, 40, 50 μg/mL	Aqueous	11-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 B	Inhibited the growth	NM	[26]
Salvia ballotiflora	Ground aerial parts	CT26	6.76 μg/mL	Hexane-washed chloroform extract	19-Deoxyicetexone, 7,20-dihydroanastomosine, icetexone, 19-deoxyisoicetexone	Cytotoxic activity	NM	[149]
Tinospora cordifolia	Stem	HCT116	1, 10, 30, 50 μM	Hydroalcoholic	Clerodane 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-diolide	Induced 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 oleracea	Fruit	NM	35 μg/mL	Hydroethanolic	Vanillic acid, orientin, isoorientin	NM	(i) Scavenging capacity towards ROO and HOCl; (ii) Inhibition of nitroso compound formation	[151]
Salvia miltiorrhiza	NM	HCT116	,	Ethanolic	Diterpene quinone	NM	Decreased levels of pro-caspases 3 and 9	[152]
Coffea	Bean	HCT116	1 mg/mL	Aqueous	Chlorogenic acid complex (CGA7)	NM	(i) DNA fragmentation, PARP-1 cleavage, caspase 9 activation, downregulation of Bcl-2 and upregulation of Bax	[153]
Illicium verum	Fruit	HCT116	10 mg/mL	Ethanolic	Gallic acid quercetin	Induction of apoptosis and inhibition of key steps of metastasis	NM	[154]
Garcinia propinqua Craib	Leaf	HCT116	NM	CH2Cl2 extract	Benzophenones, xanthones, and caged xanthones	Potent inhibitory cytotoxicities	NM	[155]
	Stem, bark	HCT116	14.23, 23.95 μM	MeOH, CH2Cl2, and EtOAc extract	Xerophenone 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 V1	NM	NM	[156]
Malus pumila Miller cv. Annurca	Fruit	Caco-2	400 mg/L	Methanolic	Chlorogenic acid, (+)catechin, (–)epicatechin, isoquercetin, rutin, phloridzin, procyanidin B2, phloretin, quercetin	WNT inhibitors and reduced WNT activity elicited by WNT5A	NM	[157]
Malus domestica cv. Limoncella	Fruit	Caco-2	400 mg/L	Methanolic	Chlorogenic acid, (+)catechin, (–)epicatechin, isoquercetin, rutin, phloridzin, procyanidin B2, phloretin, quercetin	WNT inhibitors and reduced WNT activity elicited by WNT5A	NM	[157]
Coix lacryma-jobi var. ma-yuen	Leaf	HCT116	0.5, 1 mg/mL	Aqueous	Coixspirolactam A, coixspirolactam B, coixspirolactam C, coixlactam, methyl dioxindole-3-acetate	NM	Inhibited migration, invasion, and adhesion via repression of the ERK1/2 and Akt pathways under hypoxic conditions	[158]
Mesua ferrea	Stem, bark	HCT116, HT-29	3.3, 6.6, and 11.8 μg/mL	NM	Fractions (α-amyrin, SF-3, n-Hex)	Downregulation of multiple tumor promoter	Upregulation of p53, Myc/Max, and TGF-β signaling pathways	[159]
Taraxacum	Root	SGC7901, BGC823	3 mg/mL	Aqueous	NM	NM	Proliferation and migration through targeting lncRNA-CCAT1	[160]
Portulaca oleracea	Leaf	HT-29 CSCs	2.25 μg/mL	Alcoholic	Oxalic, malic acid	NM	Inhibited expression of the Notch1 and β-catenin genes, regulatory and target genes that mediate the Notch signal transduction pathway	[161]
Hordeum vulgare L.	NM	HT-29	NM	Aqueous & juice	Protein, 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.	NM	COLO 205 and KM12	12.5 μM	Methyl ethyl ketone extract	n-Hexane, CH2Cl2, EtOAc, and MeOH fractions (A−D)	(i) Growth inhibitory activity; (ii) Antiproliferative effect	NM	[163]
Mentha×piperita	Leaf	HCT116	5, 10, 20, 30, 40, 50 μg/mL	Aqueous	Polyphenols	NM	Inhibited replication of DNA and transcription of RNA which induce the ROS	[164]
Mammea longifolia Planch. and Triana	Fruit	SW480	25, 50, 100 μg/mL	Methanolic	NM	NM	Mitochondria-related apoptosis and activation of p53	[165]
Rollinia mucosa (Jacq.) Baill.	NM	HCT116, SW-480	<4, <20 μg/mL	EtOH	Rollitacin, jimenezin, membranacin, desacetyluvaricin, laherradurin	Cytotoxic activity	NM	[54]
Annona diversifolia Saff.	NM	SW-480	0.5 μg/mL	NM	Cherimolin-2	Cytotoxic activity	NM	[54]
A. purpurea Moc. & Sessé ex Dunal	NM	HT-29	1.47 μg/mL	CHCl3-MeOH	Purpurediolin, purpurenin, annoglaucin, annonacin A	Cytotoxic activity	NM	[54]
Viguiera decurrens (A.Gray) A. Gray	NM	NM	3.6 μg/mL	Hex; EtOAc; MeOH	β-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 ronoate	Cytotoxic activity	NM	[54]
Helianthella quinquenervis (Hook.) A. Gray	NM	HT-29	2-10 μg/mL	NM	Demethylencecalin	Cytotoxic activity	NM	[54]
Smallanthus maculatus (Cav.) H. Rob.	NM	HCT15	<20 μg/mL	Acetone	Fraction F-4, fraction F-5, ursolic acid	Cytotoxic activity	NM	[54]
Bursera fagaroides (Kunth) Engl.	NM	HF6	1.8×10^-4 to 2.80 μg/mL	Hydroalcoholic	Podophyllotoxin, β-peltatin-A methyl ether, 5-desmethoxy-β-peltatin-A methyl ether, desmethoxy-yatein, deoxypodophyllotoxin, burseranin, acetyl podophyllotoxin	NM	(i) Inhibitor of microtubules; (ii) Ability to arrest cell cycle in metaphase	[54]
Viburnum jucundum C.V. Morton	NM	HCT15	<20 μg/mL	Acetone	Ursolic acid	Cytotoxic activity	NM	[54]
Hemiangium excelsum (Kunth) A.C.Sm.	NM	HCT15	<10 (μg/mL)	MeOH	PE, EtOAc, MeOH	Cytotoxic activity	NM	[54]
Hyptis pectinata (L.) Poit.	NM	Col2	<4, <20 μg/mL	NM	Pectinolide A, pectinolide B, pectinolide C, α-pyrone, boronolide, deacetylepiol-guine	Cytotoxic activity	NM	[54]
H. verticillata Jacq.	NM	Col2	<4,<20 μg/mL	NM	Dehydro-β-peltatin, methyl ether dibenzylbutyrolactone, (-)-yatein, 4-demethyl-deoxypodophyllotoxin	Nonspecific cytotoxic activity	NM	[54]
H. suaveolens (L.)	NM	HF6	2.8-12 μg/mL	Chloroform and butanol	β-Apopicropodophyllin	Nonspecific cytotoxic activity	NM	[54]
Salvia leucantha Cav.	Leaf, root, stem	HF6, HT-29, HCT15	14.9, 12.7, 9.9 μg/mL	CHCl3	NM	Cytotoxic activity	NM	[54]
Vitex trifolia L.	NM	HCT15	3.5 to <1 (μg/mL)	Hexane and dichloromethane	Salvileucalin B, Hex: leaf, Hex: stem, DCM: leaf, DCM: stem	Cytotoxic activity	NM	[54]
Persea americana Mill.	NM	HT-29	<4 μg/mL and <20 μg/mL	Ethanolic	1,2,4-trihydroxynonadecan, 1,2,4-trihydroxyheptadec-16-ene, 1,2,4-trihydroxyheptadec-16-yne	Cytotoxic activity	NM	[54]
Linum scabrellum	Roots, aerial parts	HF6	0.2, 0.5, 2.3 μg/mL	Chloroform and butanol	DCM: MeOH, 6MPTOXPTOX	NM	(i) Induction of cell cycle arrest in G2/M; (ii) Inhibition of tubulin polymerization	[54]
Phoradendron reichenbachianum (Seem.) Oliv.	NM	HCT15	3.6, 3.9, and 4.3 μg/mL	NM	Moronic acid	Cytotoxic activity	NM	[54]
Cuphea aequipetala Cav.	NM	HCT15	18.70 μg/mL	Acetone	NM	Cytotoxic inactivity	NM	[54]
Galphimia glauca Cav.	NM	HCT15	0.63, 0.50, 1.99 μg/mL	EtOH, MeOH, aqueous	NM	Cytotoxic activity	NM	[54]
Mimulus glabratus Kunth	NM	HF6	12.64 μg/mL	MeOH	NM	Cytotoxic activity	NM	[54]
Picramnia antidesma Sw.	NM	HCT15	0.6 to 4.5 μM	NM	10-Epi-uveoside, uveoside, picramnioside E, picramnioside D	Cytotoxic activity	NM	[54]
Penstemon barbatus (Cav.) Roth	NM	HF6	15.19 μg/mL	MeOH	NM	Cytotoxic activity	NM	[54]
P. campanulatus (Cav.) Willd.	NM	HF6	6.74 μg/mL	MeOH	NM	Cytotoxic activity	NM	[54]
Veronica americana Schwein. ex Benth.	NM	HF6	0.169 and 1.46 μg/mL	MeOH	NM	Cytotoxic activity	NM	[54]
Zea mays L.	NM	HCT116, SW-480, SW-620	NM	NM	13-Hydroxy-10-oxo-trans-11-octadecenoic acid	Cytotoxic activity	NM	[54]
Colubrina macrocarpa (Cav.) G. Don	NM	HCT15	10, 2.1, 9.1 μg/mL	PE, EtOAc, MeOH	NM	Cytotoxic activity	NM	[54]
Coix lacryma-jobi	Seed, endosperm, and hull	HT-29	0.1–1,000 μg/mL	Methanolic, hexane	Phytosterols (campesterol, stigmasterol, and β-sitosterol), gamma-linolenic acid (GLA), arachidonic acid (AA), eicosapentaenoicacid (EPA) and docosahexaenoic acid (DHA), linoleic acid	NM	(i) Influence of signal transduction pathways that involve the membrane phospholipids; (ii) Enhancement of ROS generation and decrease of cell antioxidant capacity	[166]
Abutilon indicum	Leaf	HT-29	210 μg/mL	Aqueous	Flavonoids (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 rhois	NM	HCT116, HT-29	12.5, 25, 50, 100, 200 μg/mL	Aqueous with steaming process	Gallotannins	Increased 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 Linné	Powder	HCT116	20, 30, 40, 60, 80, 100 μg/mL	Ethanolic	Phenolic compounds	Inhibited 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 stamen	Powder	HCT116	100, 200, 400 μg/mL	Ethanolic crude	NM	NM	(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 silk	NM	LoVo, HCT116	1.25, 2.5, 5, 10, 20 μg/mL	Aqueous	Proteins, polysaccharides, flavonoid, vitamins, tannins, alkaloids, mineral salts, steroids	NM	(i) Increase in the Bax, cytochrome c, caspases 3 and 9 levels	[171]
Lycium barbarum L.	Powder	HT-29	1, 2, 3, 4, 5 μg/mL	NM	Neoxanthin, all-trans-β-cryptoxanthin, polysaccharides, carotenoids, flavonoids	NM	(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 fruit	HT-29	1, 2.5, 5, 10, 20 μg/mL	Crude ethyl acetate	Delphinidin, cyanidin, petunidin, and peonidin	NM	(i) Increased intracellular ROS production; (ii) Decreased TNF-α, IL-1β, IL-6, and NFκB1 expressions	[173]
Zanthoxylum piperitum De Candolle	Fruit	Caco-2, DLD-1	200 μg/mL	Aqueous	NM	NM	(i) Increased the phosphorylation of c-Jun N-terminal kinase (JNK)	[174]
Celtis aetnensis (Tornab.) Strobl (Ulmaceae)	Twigs	Caco-2	5, 50, 100, 250, or 500 μg/mL	Methanolic	Flavonoid and triterpenic compounds	NM	(i) Increase in the levels of ROS; (ii) Decrease in RSH levels and expression of HO-1	[175]
Rosa canina	Peel and pulp	Caco-2	62.5, 125, 250, 500 μg/mL	Total extract (fraction 1), vitamin C (fraction 2), neutral polyphenols (fraction 3), and acidic polyphenols (fraction 4)	Polyphenols	Decreased production of reactive oxygen species (ROS)	NM	[176]
Rhazya stricta	Leaf	HCT116	47, 63, 79, and 95 μg/cm^2	Crude alkaloid	Alkaloids	NM	(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 coffee	NM	Caco-2	10-1,000 μg/mL	NM	5-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 cells	NM	[178]
Flourensia microphylla	Leaf	HT-29	NM	Ethanolic and acetone	Phenolic compounds	NM	(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.