Abstract
Several studies have suggested that a phenolic-rich diet may be protective against colon cancer. Most phenolic compounds are not absorbed in the small intestine and reach the colon where they are metabolized by gut microbiota in simple phenolic acids. In this study, the anti-proliferative activity of quercetins, chlorogenic acids, their colon metabolites and mixtures of parent compounds/metabolites was assessed by using two colon cancer cell lines (Caco-2 and SW480) at physiologically relevant concentrations. Chlorogenic acids, quercetin and the metabolite 3-(3',4'-dihydroxyphenyl)acetic acid exerted remarkable anti-proliferative activity against Caco-2, whereas quercetin derivatives and metabolites were the most active against SW480. Tested compounds arrested the cell cycle at the S phase in both the cell lines. The mixtures of parent compounds/metabolites, which mimic the colon human metabotypes that slowly or rapidly metabolize the parent compounds, similarly inhibited cell growth. SW480 cells metabolized parent phenolic compounds more rapidly and extensively than Caco-2, whereas colon metabolites were more stable. These results suggest that dietary phenolic compounds exert an anti-proliferative effect against human colon cancer cells that can be further sustained by the colon metabolites. Therefore, gut microbiota metabolism of phenolic compounds may be of paramount importance in explaining the protective effect of phenolic-rich foods against colon cancer.
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