Modulation of aberrant crypt foci and apoptosis by dietary herbal supplements (quercetin, curcumin, silymarin, ginseng and rutin)

Abstract

It is estimated that one-third of Americans use dietary herbal supplements on a regular basis. Diets rich in bioactive phytochemicals are associated with reduced risk of certain cancers, notably, colon cancer. Herbal supplements have not been directly tested as sources of bioactive cancer preventives. Hence, this study compares the ability of four herbal flavonoids (quercetin, curcumin, rutin and silymarin) and one whole herb mixture (ginseng powder) to suppress aberrant crypt foci (ACF) in an azoxymethane (AOM)-induced rat colon cancer model. Second, this study examines the effect of these herbal compounds on apoptosis and the mechanisms by which these compounds evoke apoptosis. The results of this study show that diets containing quercetin, curcumin, silymarin, ginseng and rutin decreased the number of ACFs by 4-, 2-, 1.8-, 1.5- and 1.2-fold, respectively compared with control. Histological analysis of the colon mucosa revealed that all the herbal supplements, except silymarin, induced apoptosis, with quercetin being the most potent (3x increase compared with control). Furthermore, ginseng and curcumin were region-specific in inducing apoptosis. The ability of quercetin and curcumin to modulate ACFs correlates well with their ability to induce apoptosis. Western blot analysis of caspase 9, Bax (proapoptotic) and Bcl-2 (antiapoptotic) proteins from the colon scraping suggests that quercetin and curcumin induce apoptosis via the mitochondrial pathway. Taken together, the results of this study suggest that these herbal supplements may exert significant and potentially beneficial effects on decreasing the amount of precancerous lesions and inducing apoptosis in the large intestine.

Comparative Antioxidant, Antiproliferative and Apoptotic Effects of <i>Ilex laurina</i> and <i>Ilex paraguariensis</i> on Colon Cancer Cells

“…In addition, it is possible that these anticancer effects were due to the synergistic action of chlorogenic acid with other compounds such as ursolic acid and rutin [3,4], also present in YMT. It has been reported that ursolic induced apoptosis on HT-29 cells by suppressing EGFR/MAPK pathway [22], and rutin decreased by 1.2-fold the number of aberrant crypt foci in an azoxymethane-induced CRC in rats [23].…”

Silymarin and epithelial cancer chemoprevention: How close we are to bedside?

“…In the first study, authors report that rats fed with silymarin supplemented diet led to significant decrease in number of aberrant crypt foci (represent precursor lesions for colonic adenomas) in an azoxymethane (AOM)-induced rat colon cancer model (Volate et al, 2005). In another similar but more detailed study, it was observed that silymarin administration through diet for 4 weeks either during or after carcinogen (Azoxymethane) exposure led to a significant reduction in the frequency of aberrant crypt foci formation.…”

Matrix metalloproteinases and gastrointestinal cancers: Impacts of dietary antioxidants

“…In vivo studies have been performed to depict the chemopreventive properties of quercetin on different cancers. Volate et al [188] found that food supplementation of approximately 3% quercetin exerts significantly beneficial effects by decreasing precancerous lesions through induction of cellular. Dihal et al [189] reported that quercetin inhibits azoxymethane-induced colorectal carcinogenesis in F344 rats.…”