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

• Published in: Clinical biochemistry 2001-07, Vol.34 (5), p.415-420
• Main Authors: Soleas, George J, Goldberg, David M, Grass, Linda, Levesque, Michael, Diamandis, Eleftherios P
• Format: Article
• Language: English
• Subjects: (+)-Catechin; Antioxidants - pharmacology; Apoptosis; Breast Neoplasms - metabolism; Caffeic acid; Caffeic Acids - pharmacology; Cancer; Catechin - pharmacology; Colonic Neoplasms - metabolism; Flavonoids; Fluoroimmunoassay; Gene Expression Regulation, Neoplastic; Genes, p53 - genetics; Humans; Models, Structural; p53; Phenols - pharmacology; Polymers - pharmacology; Polyphenols; Quercetin; Quercetin - pharmacology; Quercetin - toxicity; Resveratrol; Stilbenes - pharmacology; Time Factors; Time-resolved fluorescence immunoassay; Trans-Resveratrol; Tumor Cells, Cultured; Wine; Wine - analysis
• ISSN: 0009-9120; 1873-2933
• DOI: 10.1016/S0009-9120(01)00246-6

Background: The p53 gene is an established tumor suppressor and an inducer of apoptosis. We here attempt to determine whether the putative anticarcinogenic properties attributed to red wine and its polyphenolic constituents depend, at least in part, upon their ability to modulate p53 expression in cancer 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 which, p53 concentrations were measured in cell lysates by a time-resolved fluorescence immunoassay. Results: None of the polyphenols tested affected p53 expression in the breast cancer cell lines T-47D and MDA-MB-486. p53 content of MCF-7 breast cancer cells (wild-type) was increased by caffeic acid, decreased by resveratrol, and showed a twofold increase with catechin, that reached borderline statistical 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 being 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 lines. Conclusions: The observed p53 concentration changes upon stimulation by polyphenols 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 reasons, we speculate that the putative anticarcinogenic properties of wine polyphenols are unlikely to be mediated by modulation of p53 gene expression.