Wine antioxidant polyphenols inhibit the proliferation of human prostate cancer cell lines

The effect of different wine antioxidant polyphenols (catechin, epicatechin , quercetin, and resveratrol) on the growth of three prostate cancer cell l ines (LNCaP, PC3, and DU145) was investigated A dose- and time-dependent in hibition of cell growth by polyphenols was found at nanomolar concentration s. The proliferation of LNCaP and PC3 cells was preferentially inhibited by flavonoid's (catechin, epicatechin, and quercetin), whereas resveratrol wa s the most potent inhibitor of DU145 cell growth. Possible mechanisms of ac tion were investigated. 1) The competition of polyphenols for androgen bind ing in LNCaP cells revealed significant interaction only in the case of hig h concentrations of quercetin, at least at five orders of magnitude higher than the concentrations needed for cell growth inhibition. All other phenol s showed low interactions. 2) Oxygen species production after mitogen stimu lation and H2O2 sensitivity of these cell lines did not correlate with the observed antiproliferative effects, ruling out such a mode of action. 3) NO production revealed two different patterns. LNCaP and DU145 cells produced high concentrations of NO, whereas PC3 cells produced low concentrations. Phorbol ester stimulation of cells did not reveal any additional effect in LNCaP and DU145 cells, whereas it enhanced the secretion of NO in PC3 cells . Polyphenols decreased NO secretion. This effect correlates with their ant iproliferative action and the inhibition of inducible NO synthase. It is th erefore proposed that the antiproliferative effect of polyphenols is mediat ed through the modulation of NO production. rn conclusion, our data show a direct inhibitory effect of low concentrations of antioxidant wine phenols on the proliferation of human prostate cancer cell fines mediated by the pr oduction of NO, further suggesting potential beneficial effects of wine and other phenol-containing foods or drinks for the control of prostate cancer cell growth.