Do wine polyphenols modulate p53 gene expression in human cancer cell lines?

Background: The p53 gene is an established tumor suppressor and an inducer of apoptosis. We here attempt to determine whether the putative anticarcino genic properties attributed to red wine and its polyphenolic constituents d epend, at least in part, upon their ability to modulate p53 expression in c ancer cells. Methods: Three human breast cancer cell lines (MCF-7, T47D; MDA-MB-486) and one human colon cancer cell line [Colo 320 HSR (+)] were treated for 24-h with each of four polyphenols [quercetin; (+)-catechin, trans-resveratrol; caffeic acid] at concentrations ranging from 10(-7) M to 10(-4) M, after wh ich, p53 concentrations were measured in cell lysates by a time-resolved fl uorescence immunoassay. Results: None of the polyphenols tested affected p53 expression in the brea st cancer cell lines T-47D and MDA-MB-486. p53 content of MCF-7 breast canc er cells (wild-type) was increased by caffeic acid, decreased by resveratro l, and showed a twofold increase with catechin, that reached borderline sta tistical significance; however, none of these effects were dose-responsive. Colo 320 HSR (+) cells (with a mutant p53 gene) had lower p53 content upon stimulation, reaching borderline statistical significance, but without bei ng dose-responsive, in the presence of caffeic acid and resveratrol. Apart from toxicity at 10(-4) M, quercetin had no effect upon these four cell lin es. Conclusions: The observed p53 concentration changes upon stimulation by pol yphenols are relatively small, do not follow a uniform pattern in the four cell lines tested, and do not exhibit a dose-response effect. For these rea sons, we speculate that the putative anticarcinogenic properties of wine po lyphenols are unlikely to be mediated by modulation of p53 gene expression. (C) 2001 The Canadian Society of Clinical Chemists. All rights reserved.