Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

Possible role of resveratrol in prevention of prostate carcinogenesis

JM Wu PhD 1, TC Hsieh PhD 1

Dept Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY,

AIMS: Management of metastatic prostate cancer poses a significant challenge to clinicians because of its hormone refractoriness and resistance to conventional chemotherapies. Resveratrol is a polyphenol found in grape skin and various foods that was shown to inhibit initiation, promotion, and progression of tumorigenesis. We aim to investigate the possibility of using resveratrol as a chemically-defined prophylactic and therapeutic agent for the prevention and treatment of metastatic prostate cancer. METHODS: Hormone-sensitive LNCaP and hormone-refractory DU-145, PC-3 and JCA-1 cells were treated with various concentrations of resveratrol. Cell number, cell cycle traverse, and changes in state of acetylation and phosphorylation of p53 were evaluated. RESULTS: Resveratrol effectively suppressed growth of all prostate cancer cells. Expression of PSA, a prostate specific protein used as a marker to monitor responsiveness of prostate cancer patients to various treatment modalities, was significantly down-regulated by resveratrol, via an AR-independent mechanism. The antiproliferative effects of resveratrol are partly due to disruption of cell cycling and induction of apoptosis. In JCA-1 cells, overall expression of p53 was not affected, while a significant increase in acetylation, and phosphorylation at serine-15, were observed in cells following 3 day treatment with resveratrol. CONCLUSIONS: Resveratrol regulates cell proliferation by multiple mechanisms, one of which involves stabilization of p53. By acting as a pleitropic prostate cancer cell regulator, resveratrol offers promise as a novel and non-toxic alternative therapeutic agent for advanced prostate cancer.

KEY WORDS: Resveratrol, p53, prostate cancer.

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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on chemotherapy & chemoprevention.