Table 2.

Preclinical studies of effect of flavonoids on colon tumorigenesis.

Type of Flavonoid	Class	Dose	Model	Results	Reference
Black raspberry anthocyanin extract	Anthocyanidin	5% or 10% extract, or 3.5 µmol/g and 7.0 µmol/g anthocyanin concentration in diet	Azoxymethane (AOM)/dextran sulfate sodium (DSS) model of C57BL/6 mice	Reduction in colon carcinogenesis; reduction of pathogenic bacteria	[133]
Black raspberry-derived anthocyanins	Anthocyanidin	0.5, 5 and 25 µg/mL	Human colorectal carcinoma cell line HCT116, Caco2, and SW480 cells	Suppressed activity and protein expression of DNMT1 and DNMT3B	[134]
Cyanidin and delphinidin	Anthocyanidin	25–100 µM	Human colorectal carcinoma cell line Caco-2, LoVo/ADR cells	Induced cell death	[128]
Delphinidin	Anthocyanidin	30–240 µM	Human colon cancer HCT116 cells	Induced cell death; inhibition of NFκB	[130]
Dried bilberries or 1 or 10% anthocyanins (ACs)	Anthocyanidin	1 and 10% ACs	Acute and chronic dextrane sodium sulphate (DSS) colitis of Balb/c mice	Amelioration of acute as well as chronic colitis	[131]
Mirtoselect, an anthocyanin mixture from bilberry	Anthocyanidin	0.1% and 0.3% (w/w) ACs in diet	Apc(Min) mice, a genetic model of human familial adenomatous polyposis	Reduced adenoma load dose-dependently	[135]
Apigenin	Flavone	50–80 µM	Human coloncarcinoma cell lines SW480, HT-29, and Caco-2	Cell-cycle arrest at G2/M; p34(cdc2) and decreased cyclin B1 protein expression	[143]
Apigenin analogs (acacetin, chrysin, kampherol, luteolin, myricetin, naringenin, and quercetin)	Flavone	40–80 µM	Human SW480 and Caco-2 colonic carcinoma cells	G2/M cell-cycle arrest	[144]
Apigenin	Flavone	20–80 µM	HT29-APC cells	G2/M cell-cycle arrest; induction of APC protein expression	[145]
Apigenin	Flavone	10 µM in vitro; 25 and 50 mg/kg in vivo	Human colorectal cancer cells HCT-116, SW480, HT-29 and LoVo; APCMIN+ mice	Reduced polyp numbers; increased p53 activation	[148]
Apigenin and quercetagetin	Flavone	200 µM	Human colorectal colon cancer (SW480) cells	Inhibition of cell proliferation; alter the expression of bax and bcl2 transcription	[149]
Apigenin	Flavone	50 µM	HCT116 human colon cancer cells	Apoptosis- and autophagy-inducing effects	[146]
Apigenin	Flavone	1.5626–100 µM	Colorectal cell lines HT-29 and HCT-15	Pro-oxidative stress induction	[147]
Apigenin	Flavone	25–100 µg/mL	Human gut bacteria	Inhibited Enterococcus caccae growth; up-regulated genes involved in DNA repair, stress response, cell wall synthesis, and protein folding	[165]
Quercetin	Flavonol		Human colon cancer COLO320 DM cells	Inhibited cell growth	[170]
Quercetin and rutin	Flavonol	2% quercetin; 4% rutin in diet	Azoxymethane (AOM)-induced colonic neoplasia in mice	Reduced hyperproliferation of colonic epithelial cells and focal areas of dysplasia (FAD) incidence	[175]
Quercetin and rutin	Flavonol	2% quercetin; 4% rutin in diet	AOM-induced colonic neoplasia in mice	Reduced FAD	[178]
Quercetin	Flavonol	25–100 µM	HT-29 and SW480 colon cancer cells	Inhibited cell growth and promoted apoptosis; down-regulated ErbB2/ErbB3 signaling and Akt pathway	[166]
Quercetin	Flavonol	5–50 µM	Caco-2 cells	Induced cell cycle arrest; downregulated expression of cell cycle genes	[168]
Quercetin	Flavonol	100 µM	SW480 cells	Inhibited the transcriptional activity of β-catenin/Tcf	[172]
Quercetin, curcumin, rutin, and silymarin	Flavonol	30,000, 50, 8000, and 5000 p.p.m, respectively	AOM-induced rat colon cancer model	Decreased precancerous lesions and induced apoptosis	[177]
Quercetin	Flavonol	15–40 µM	SW480 cells and clone 26 cells	Inhibition of expression of cyclin D1 and survivin as well as the Wnt/β-catenin signaling pathway	[169]
Quercetin	Flavonol	4.5 g/kg diet	Azoxymethane (AOM)-induced rat colon cancer model	Suppressed formation of early preneoplastic lesions in colon carcinogenesis	[176]
Quercetin	Flavonol	100 µM in vitro; 50–100 mg/kg in vivo	HT-29 colon cancer cells in vitro, and xenografts	Reduced tumor growth and induced apoptosis via 5’-AMP kinase (AMPK) activation and p53-dependent apoptotic cell death	[167]
Quercetin	Flavonol	50 µM	Human colon adenocarcinoma derived cell lines Caco2 and DLD-1	Inhibited cellular proliferation associated with increased expression of the endocannabinoid receptor (CB1-R)	[174]
Quercetin, catechin, and puerarin	Flavonol	0.15 g/L culture	Gut microbiota in vitro cultures	Affected relative abundances of various bacteria	[179]
Quercetin	Flavonol	10 mg/kg	DSS induced colitis model in C57BL/6J mice	Ameliorated colitis	[180]
Epigallocatechin-3-gallate (EGCG)	Catechin	0.01% and 0.1% green tea extract	Azoxymethane-induced colon carcinogenesis in the rat	Inhibited chemical carcinogenesis of the gastrointestinal tract	[206]
Epigallocatechin-3-gallate (EGCG)	Catechin	100 µM	Human colorectal carcinoma HT-29 cells	Inhibited cell growth and induced apoptosis associated with JNK activation	[197]
Epigallocatechin-3-gallate (EGCG)	Catechin	50–300 µM	Human colorectal cancer cell lines HT-29 and HCA-7	Reduced cellular proliferation; inhibition of COX-2 and downregulation of NF-κb, ERK1/2, and Akt pathways	[196]
Epigallocatechin-3-gallate (EGCG)	Catechin	0.1%	AOM-induced rat colon cancer model	Decreased tumor numbers associated with Inhibition of indoleamine 2,3-dioxygenase (IDO) activity	[205]
Epigallocatechin-3-gallate (EGCG)	Catechin	50–150 µM	HCT 116 human colon cancer cells	Reduced histone deacetylase (HDAC) and DNMT protein expression	[203]
Epigallocatechin-3-gallate (EGCG)	Catechin	50–200 µM	5-fluorouracil (5FU)-resistant (5FUR) CRC cells and spheroid-derived CSC (SDCSC) xenograft model	Suppressed Notch1, Bmi1, Suz12, and Ezh2; inhibited tumor growth in a xenograft model	[193]
Epigallocatechin-3-gallate (EGCG)	Catechin	50–150 µM	CIMP+ cell lines	Reduced cell viability; induced cell cycle arrest; Decreased DNMT activity resulting in promoter methylation changes at several cancer-related genes such as retinoid X receptor alpha (RXRα)	[204]
Epigallocatechin-3-gallate (EGCG)	Catechin	10–60 µM	Human colon cancer cell lines DLD-1 and SW480	Inhibition of spheroid formation with suppression of proliferation and Wnt/β-catenin pathway	[194]
Epigallocatechin-3-gallate (EGCG)	Catechin	5–40 µg/mL	Colon adenocarcinoma cells COLO205	Induced chromosome instability and triggered apoptosis and inhibition of cell division	[198]

JNK: c-Jun N-terminal kinase; ERK: extracellular signal-regulated kinase; DNMT: DNA methyltransferase.