Cytotoxicity of extracts reported against breast cancer (MCF-7), hepatocellular carcinoma (HepG2), and cervical carcinoma (HeLa) cell lines [51]. Isoquercitrin inhibited urinary bladder, pancreatic, and colon cancer progress [52–54]
Extracts induced significant cell growth inhibition (63%) in human breast cancer (MCF-7) and skin fibroblast (CCD-1059 sk) cells. The expression of proapoptotic caspase-3, caspase-9, and p21 genes was increased in MCF-7 cells [55]
Albizia coriaria (Welw. ex Oliver)
Oleanane-type saponins (coriarioside A and coriarioside B), gummiferaoside C, acacic acid glycosides, lupeol (3), lupenone, betulinic acid, acacic acid lactone, (+) – catechin, and benzyl alcohol [56–58]
Cytotoxicity (IC50 > 500 μg/ml) against human embryonic lung fibroblast (HELF) cells [59]. Coriarioside A and gummiferaoside C from root bark showed cytotoxicity against two colorectal human cancer cells: HCT116 (with IC50 of 4.2 μM for coriarioside A and 2.7 μM for gummiferaoside C) and HT-29 (with IC50 6.7 μM for coriarioside A and 7.9 μM for gummiferaoside C) cell lines [56]
Extracts exhibited an antiproliferative effect on human cancer cell lines, including liver (HepG2), colon (Caco2), prostate (PC-3), and breast (MCF-7) cancer cells [61]. Extracts induced G2/M-phase cell cycle arrest in EJ bladder cancer cells [62]. DATS suppressed the proliferation of SGC-7901 gastric cancer cells [63]
SAC induced cell cycle arrest in A2780 human epithelial ovarian cancer cells [64]. S-propargyl-l-cysteine (SPRC), an analogue of SAC, reduced the proliferation of human pancreatic ductal adenocarcinoma cells and induced cell cycle arrest [65]. Garlic derived S-allylmercaptocysteine (SAMC) suppressed the proliferation of hepatocellular carcinoma cells [66]. SAMC inhibited the proliferation of human colorectal carcinoma SW620 cells [67]
Allicin inhibited the proliferation of gastric adenocarcinoma cells by inducing cell cycle arrest [68]. Ajoene was shown to restrain the growth of glioblastoma multiforme cancer stem cells and human breast cancer cells [69]
Annonaceous acetogenins exhibited antiproliferative activity against human prostate cancer PC-3 cells [70]. Fruit extracts are cytotoxic against U937 histiocytic lymphoma cell lines with IC50 of 10.5, 18.2, and 60.9 μg/ml for ethyl acetate, hexane, and methanol extracts respectively [74]
Annonacin caused complete suppression of 7,12-dimethylbenz[a]anthracene (DMBA) induced and 12-0- tetradecaboylphorbol-13-acetate (TPA) promoted skin tumorigenesis in mice [75]
At 0.1 μM, annonacin induced growth arrest and apoptosis in breast cancer (MCF-7) cells [76]
Annomuricin E was cytotoxic to HT-29 colon carcinoma and CCD841 normal colon cell lines with IC50 values of 5.72, 3.49, and 1.62 μg/mL for HT-29 cells at time intervals of 12, 24, and 48 hours of administration, respectively [77]
Stem extracts suppressed the expression of molecules associated with hypoxia and glycolysis in CD18/HPAF (pancreatic) cancer cells (IC50 of 73.0 μg/mL) [78]
Aqueous leaf extracts exhibited anticancer activity with IC50 values of 220, 350, and 250 μg/mL for breast cancer cell lines: MCF7, MDA-MB231, and 4T1, respectively [79]. Leaf extracts recorded cytotoxicity against human bladder cancer (K562) and leukemia cancer (ECV304) cell lines [80]
Cytotoxicity recorded against Raji cells with IC50 values of 90.6, 407.2, and 260.2 μg/mL. Cytotoxic effect of chloroform and n-hexane extracts on HeLa cell lines gave IC50 values of 127.3 and 169.2 μg/mL, respectively [81]
Leaf extracts inhibited cell proliferation in pancreatic cancer cells (capan-1) [82]
Ethanol extract of seeds showed a cytotoxic effect on MDBK and HEp-2 cells (IC50 values:34.5 and 55 mg/mL, respectively) at 24 h, and an IC50 value of 49.6 × 10−3 mg/mL toward HEp-2 cells at 72 h [83]
Cytotoxic against kidney epithelial (VERO), stomach cancer (C-678), and human large lung cell carcinoma (H-460) cell lines with IC50 values lower than 0.00022 mg/mL for all the cell lines [84]. Cytotoxicity was reported against histiocytic lymphoma cell lines (U937), pancreatic cancer cells (FG/COLO357), breast cancer cells (MDA-MB-435S), immortalized human keratinocytes (HaCat), normal human liver cells (WRL-68), and human skin malignant melanoma (A375) [73, 78, 85–87]. In histiocytic lymphoma cell lines, the extract had an IC50 value of 7.8 μg/mL. Toxicity toward FG/COLO357 with an IC50 value of 200 μg/mL [78]. Cytotoxic effect of n-butanolic extract of leaves against MDA-MB-435S (human breast carcinoma), HaCaT (human immortalized keratinocyte), and WRL-68 (normal human hepatic) cell lines with IC50 values of 29.2, 30.1, and 52.4 μg/mL, respectively [73]
Ethanol extracts of leaves cytotoxic to Ehrlich Ascites carcinoma (EACC) and breast cancer (MDA and SKBR3) cell lines with IC50 values of 335.85, 248.77, and 202.33 μg/mL [88]. Fruit extracts had substantial repression of breast cancer cells (MDA-MB-468) growth as well as selective suppression of epidermal growth factor receptor (EGFR) with IC50 of 4.8 μg/mL [89]
Acetonitrile extract inhibited the viability of breast (MDA-MB-231 and MCF-7), pancreas (MIA PaCa-2), prostate (PC-3), and non-small-cell lung cancer (A459) cells. The extracts inhibited cancer cell proliferation, decreased tumor growth, and induced apoptosis in vivo in triple negative breast cancer (MDA-MB-231) xenografts grown on the chick chorioallantoic membrane (CAM) assay as well as in nude mice [91]. Hydroalcoholic extract had a cytotoxic effect in a dose-dependent manner against D-17 canine osteosarcoma cell lines better than pure artemisinin, indicating a possible synergistic effect of the phytocomplex and a mechanism of action involving iron and possibly ferroptosis [92]
The ethanolic extract exhibited significant anticancer activity against lung cancer (A549) cell line but only a slight effect against colorectal adenocarcinoma (Caco-2) cell line at 800 μg/mL [94]. Cytotoxicity against PC-3 cells led to a decrease in the growth rate of the cells (3.7% in 3 days) at 29 μg/mL. Comparative cytotoxicity tests in normal human skin (FC) and liver (HC) cell lines showed that the extracts were cytotoxic on the cells, though the activity was lower than that of doxorubicin (8.6% compared to 100%, respectively, at 29 μg/mL concentration in a 3-day test period) [95]
THC and other cannabinoids exhibited antitumor effects in animal models of cancer [99]. The acetone extract exhibited more anticancer activity against breast adenocarcinoma (MCF-7), the glioblastoma (SF-268), and the colon adenocarcinoma (HT-29) cells [100]
Cytotoxicity test on leukemia (CCRF-CEM) cells at 40 μg/mL showed that leaves and bark extracts induced more than 50% growth of this cell line. Fruit mesocarp oil extract and seed kernel oil extracts are expected to be vital for chemoprevention of cancers and other oxidative damage-induced diseases [104]
Aqueous fruit extracts exhibited anticancer activity (though lower than capsaicin standard) when tested against prostate (PC-3) and breast (MCF-7) cancer cell lines in vitro [105]
Pure lycopene and papaya juice inhibited the viability of liver cancer (HepG2) cell line with IC50 of 22.8 μg/mL and 20 mg/mL [108]. n-hexane seed extract dose-dependently inhibited superoxide generation (IC50 = 10 μg/mL) and the viability of acute promyelocytic leukemia (HL-60) cells (IC50 = 20 μg/mL), comparable to that of pure benzyl isothiocyanate [109]
Aqueous extract of flesh (0.01–4% v/v) inhibited the proliferation of breast cancer cell line (MCF-7) [110]. Ethanolic extract of the pericarp (50–640 μg/mL) inhibited the growth of breast cancer cell line (MCF-7) treated with sodium nitroprusside, a nitric oxide donor [111]. Breast cancer cell line (T47D) was inhibited by leaf protein fraction with IC50 = 2.8 mg/mL) and induced apoptosis by regulation of protein expression [112]
Aqueous extracts of leaves (1.25–27 mg/mL) exhibited a concentration-dependent anticancer effect on stomach cancer cell line (AGS), pancreatic cancer cell line (Capan-1), colon cancer cell line (DLD-1), ovarian cancer cell line (Dov-13), lymphoma cell line (Karpas), breast cancer cell line (MCF-7), Neuroblastoma cell line (T98G), uterine cancer cell line (HeLa), and T-cell leukemia cell line (CD26 negative or negative Jurkat) cell lines and suppressed DNA synthesis by suppressing the incorporation of 3H-thymidine [113]
Aqueous extract of leaves (0.625–20 mg/mL) inhibited the proliferative responses of both haematopoietic and solid tumor cell lines (T-cell lines, H9, Jurkat, Molt-4, CCRF-CEM, and HPB-ALL), Burkitt’s lymphoma cell lines (Ramos and Raji), chronic myelogenous leukemia cell line (K562), cervical carcinoma cell line (HeLa), hepatocellular carcinoma cell lines (HepG2 and Huh-7), lung adenocarcinoma cell line (PC-14), pancreatic epithelioid carcinoma cell line (Panc-1), mesothelioma cell lines (H2452, H226, and MESO-4), plasma cell leukemia cell line (ARH77), anaplastic large cell lymphoma cell line (Karpas-299), breast adenocarcinoma cell line (MCF-7), mesothelioma cell line (JMN), and pancreatic adenocarcinoma cell line (Capan-1). In peripheral blood mononuclear cells, the extract reduced the production of IL-2 and IL-4 whereas it increased the production of Th1 types cytokines such as IL-12p40, IL-12p70, INF-, and TNF-. The expression of 23 immunomodulatory genes was enhanced by the addition of papaya extract [114]
Leaf juice not only exhibited a stronger cytotoxic effect on human squamous cell carcinoma (SCC25 cancer) cells but also produced a significant cancer-selective effect as shown by tests on noncancerous human keratinocyte HaCaT cells [115]
Cytotoxicity with LC50 of 6.7 μg/ml in brine shrimp assay [97, 118, 119]
Vindoline from leaf extracts was cytotoxic to HCT-116 colorectal carcinoma cell line at 200 μg/mL [120]
Citrus reticulata Blanco, 1837
Limonin, isolimonexic acid methyl ether, ichangin, deacetylnomilin, and obacunone [121]
In vitro tumor cytotoxicity of different varieties against gastric cancer cell lines (SGC-7901, BGC-823, and AGS) recorded IC50 ranging from 20.49 to 368.40 μg/mL [122]. Antiangiogenic effect was reported [123]
Cymbopogon citratus (DC) Stapf
Citral (neral and geranial), geraniol and β-myrcene, 6-methyl-5-hepten-2-one, and undeca-2-one [124]. Oils contain geranial, neral, myrcene, and beta-pinene [125]
Essential oil exhibited protective action against N-butyl-N-(4-hydroxibuthyl)nitrosamine-induced DNA damage and a potential anticarcinogenic activity against mammary carcinogenesis in 7,12-dimethylbenz(a) anthracene, 1,2-dimethylhydrazine initiated female Balb/C mice [124]. In synergy with Taraxacum officinale root extract induced apoptosis in prostate cancer cells (DU-145 and PC-3). The lowest combination dosage of taxol treatment (0.01 μM with 0.01 mg/mL extract) showed comparable induction of apoptosis to the highest individual treatment dosage of taxol (0.5 μM) [20]
Chemopreventive against 7,12-dimethyl Benz(a)anthracene-induced squamous cell carcinoma in mice [126]. The aqueous extract has anticancer activity against human promyelocytic leukemia HL-60 cells. Oil extract is chemopreventive against induced skin cancer [128]. Apoptosis was recorded with colon and breast human cancer cell lines; pentane oil fraction showed a cytotoxic effect on human breast adenocarcinoma cell lines MDA-MB-231 and MCF-7, causing cell cycle arrest and increased apoptosis mediated through the Erk pathway [129]
Elaeodendron buchananii (Loes.)
Steroidal glycosides, eudesmane-type sesquiterpenoid, and dammarane triterpenoids: elabunin (21) [130–132]
Elabunin exhibited moderate cytotoxic activity with a median effective dose (ED50) of 100 μg/mL against L- 1210 leukemic cells [132]
Erythrina abyssinica Lam. ex DC.
Erythrina alkaloids: erythraline, erysodine, erysotrine, 8-oxoerythraline, and 11-methoxyerysodine [133]
Cytotoxicity with LC50 value > 240 μg/ml [134]. In vitro cytotoxicity of the crude alkaloidal fraction reported against HeLa, Hep-G2, HEP-2, HCT-116, MCF-7, and HFB4 cell lines with IC50 values of 13.8, 10.1, 8.16, 13.9, 11.4, and 12.2 μg/mL [133]
Euclea natalensis A.DC.
Mamegakinone, diospyrin (22) and 7-methyljuglone from root bark, lupeol,-sitosterol, 20(29)-lupene-3-isoferulate, Isodiospyrin, 5-hydroxy-4-methoxy-2-nathaldehyde, 80-hydroxydiospyrin, neodiospyrin, methylnaphthazarin, euclanone, octahydroeuclein, shinanolone, diospyrin, and natalenone [135–137]
Cytotoxicity of ethanolic roots and stem extracts reported in brine shrimp lethality test [138]
Cytotoxicity of crude chloroform extract of the roots, diospyrin, and 7-methyljuglone reported against green monkey kidney cells (VERO) and a mouse macrophage cell line, J774A.1. Crude extract and diospyrin had IC50 values of 64.87 and 17.78 μg/mL while 7-methyljuglone effected a 90% reduction of growth of Mycobacterium tuberculosis Erdman within J774.1 macrophage at 0.57 μg/mL [139]
Cytotoxicity of 7-methyljuglone from the root and a series of its derivatives on MCF-7, HeLa, SNO, and DU 145 human cancer cell lines had IC50 values ranging from 5.3 to 10.1 μM [135]
Kigelia africana Lam. Benth.
Lapachol, 3-(2′- hydroxyethyl)-5-(2″-hydroxypropyl) dihydrofuran-2-(3H)one, specioside, verminoside, and minecoside, kigelin, β-sitosterol, 1,3-dimethylkigelin, and ferulic acid
Seed oil suppressed human colon adenocarcinoma (Caco-2) and human embryonic kidney (HEK-293) cell growth in a dose-dependent manner [140]
An 80% methanol extract of the roots exhibited cytotoxicity to brine shrimps with LC50 of 7.2 μg/ml [138]
Fruit extracts increased the sub-G1 phase (apoptosis) population in HCT116 human colon cancer cells [141]
Markhamia lutea (Benth.) K. Schum
Cycloartane triterpenoids, musambins A–C and their 3-Oxyloside derivatives musambiosides A–C [142], Oleanolic acid, pomolic acid, 2-epi-tormentic acid, musambin A, and b-sitosterol-3-O-b-D-glucopyranoside [143, 144]
Anticancer activity against Ehrlich ascites carcinoma cells with an IC50 value of 27.0 μg/mL [143]. Cytotoxicity against KB (mouth epidermoid carcinoma) and the human diploid embryonic lung cells (MRC5) though most IC50 values were >50 μg/mL [144]
Cytotoxic against colon cancer (Colo-320 DM), breast cancer (MCF-7), ovary cancer (PA-1), and oral cancer (KB-403) cell lines with IC90 value of 3.98, 17.60,12.86, and 8.40 μg/mL, respectively [145]. Methanol extracts were cytotoxic to human B-lymphocyte plasmacytoma (U266B1) cell line with IC50 of 0.32 μg/ml [147]. Aqueous leaf extract caused a dose-dependent decrease in HeLa cell viability with IC50 of 70 μg/mL [148]. Leaf extracts displayed significant antiproliferative activity () against human liver (hepatocellular carcinoma, Hep-G2) and muscular (rhabdomyosarcoma, RD) cell lines [149]. The IC50 of leaf extracts cytotoxicity on cisplatin-resistant ovarian cancer (A2780CP20) and prostate cancer (PC3) cell lines in a study was 0.27 and 0.17 mg/mL, respectively [150]
Apoptosis assay performed using leaf and bark extracts on breast and colorectal cancer lines showed a remarkable increase in the number of apoptotic cells with a sevenfold increase in breast (MD-MB-231) cell line to an increase of several folds in colorectal cancer (HCT-8) cell line [146]
Leaf extracts inhibited the growth of hepatocarcinoma (HepG2), colorectal adenocarcinoma (Caco-2), and breast adenocarcinoma (MCF-7) cell lines with dichloromethane leaf extract having IC50 between 112 and 133 μg/ml [151]. Leaf extracts caused the death of 72–82% of acute myeloid leukemia cells and 77–86% of acute lymphoblastic leukemia cells after 24 hours of incubation with 20 μg/ml of the extract. At the same time, 69–81% of HepG2 cells died after treatment with ethanol extract [152]. Leaf extracts also showed in vitro anticancer activity on human hepatocellular carcinoma (HepG2) cells. At a maximum dose of 200 mg/kg, the survival of HepG2 and non-small-cell lung cancer (A549) cells was reported to decrease by 60% and 50%, respectively [153]
Leaf extract had anticancer activity against human epidermoid cancer (Hep2) cell line with IC50 of 12.5 μg/mL in the most active fraction [154]. Cytotoxicity of water-soluble leaf extract was reported against human alveolar epithelial cells derived from the lung cancer (A549) cell line with IC50 of 166.7 μg/mL [155]
Cell viability of leaf extract-treated A549, HepG2, CaCo2, Hek293, and Jurkat cells was reported to be reduced with IC50 from 0.05 to 0.4% [156]
Human pancreatic cancer cells (Panc-1, p34, and COLO-357) were inhibited by leaf extracts with IC50 of 1.1, 1.5, and 1.8 mg/mL [157]
Seed extracts had cytotoxic potential against A549, Hep-2, HT-29, and IMR-32 cancer cell lines [158]. β-sitosterol-3-oglucopyranoside, 4-(α-L-rhamnosyloxy) benzyl isothiocyanate, and niazimicin prevented the induction of Epstein–Barr virus genome in Raji cells. Niazimicin delayed the formation of tumors and reduced the number of tumors in vivo [159]
Opuntia species
Quercetin, kaempferol-3-O-rutinoside, isorhamnetin-3-O-rutinoside, betanin, and indicaxanthin [160]
Fruits, peels, seed, cladode, stem, and root extracts of different species have cytotoxicity against mammary (MCF-7), prostate (PC3), colon (Caco2, SW-480, HT-29), HeLa cervical carcinoma, myeloid leukemia (K562), and hepatic (HepG2) cell lines [161–164]
Oxalis corniculata Linn.
Palmitic, 8 oleic, linoleic, linolenic, stearic, tartaric, and citric acids, flavones (acacetin and 7,4′-diOMe apigenin), glycoflavones (4′-OMe vitexin, 4′-OMeiso-vitexin and 3′,4′-diOMe orientin), flavonols (3′,4′-diOMe quercetin), and phenolic acids such as p-hydroxybenzoic, vanillic, and syringic acids [165]
The ethanolic extract inhibited tumor growth of Ehrlich ascites carcinoma (EAC) induced in Swiss albino mice [166]
Antiprostate cancer activity targets fast dividing cells by impairing mitosis or by causing target cells to undergo apoptosis [169, 170]. There was growth inhibition of a human prostate cancer cell line (PC-3) and epithelial cells derived from a lymph-node carcinoma of the prostate (LNCaP) by 50% at 2.5 μL/mL and also induced significant apoptosis in both cell lines (PC-3 and LNCaP) at 2.5 μL/mL compared to untreated cells. The ethanolic extract had an antimitogenic effect on prostate cancer cells by inhibiting the mitogenic action of epidermal growth factor which resulted in a decreased number of cells entering the S-phase of the cell cycle [171]
Zanthoxylum chalybeum Engl.
Skimmianine, furoquinoline alkaloid skimmianine, the benzophenanthridine alkaloids chelerythrine and nitidine, the aporphine alkaloids tembetarine, magnoflorine, N-methylcorydine, N-methylisocorydine (menisperine), and berberine and the phenylethylamine candicine, alkamide, fagaramide, dihydrochelerythrine, lupeol, and sesamin [172]
Extracts showed moderate cytotoxicity with IC50 values below 50 μM against the drug-sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 leukemia cell lines [172]
Stem bark extracts exhibited potential cytotoxicity effect with LC50 value of 5.74 μg/mL in brine shrimp assay [173]
Cytotoxicity reported against human cancer cell line HL-60 cells with IC50 of 137.31 μg/mL and selectivity index of 3.81 [174]. Cytotoxicity against human gingival fibroblasts cells with IC50 of 26 ± 3 μg/mL [175]
Cytotoxicity of root bark extracts reported with IC50 of 38.5, 68.9 and < 500 μg/mL in brine shrimp toxicity assay [97, 134, 176]
IC50: -median inhibitory concentration/half maximal inhibitory concentration, LC50: median lethal concentration, and IC90: concentration inhibiting 90% of cellular growth.
