The moderate consumption of red wine has been proposed to reduce the incidence of colorectal cancer. Its anti-cancer action my in part be mediated by the actions of polyphenols on colon cancer epithelial cells. We show that a red wine phenolic (50 mu g/ml) extract devoid of anthocyanins (removed to reflect polyphenol bioavailability to the large intestine) and the major red wine flavonols quercetin, myricetin, laricitrin and syringetin (50 mu M) are capable of inhibiting the proliferation of colorectal epithelial adenocarcinoma cells. This anti-proliferative activity was partly mediated by the direct cytotoxic actions of flavonols and also their ability to cause a significant cell cycle blockage in G2/M. The anti-proliferative effects induced by flavonols were preceded, in most cases, by a strong and significant reduction of cyclooxygenase-2 (COX-2) and cyclin D1 expression. These results indicate that the observed inverse correlation between colon cancer and a moderate red wine intake may be partly mediated by the actions of red wine flavonols on the growth of cancer cells.