Prostate cancer is the second leading cause of cancer death among men in the western world. Prostate cancer is linked to elevated levels of steroid hormones, such as androgens and estrogens, and growth factors, such as insulin-like growth factor-1. These hormones and growth factors stimulate the proliferation of prostate cancer cells through the activation of receptor-mediated signaling pathways. Resveratrol, a phytochemical mainly found in grapeskin and red wine, is attributed with many of health benefits, including protection against certain cancers, cardiovascular disease and aging.
In vitro experiments provide support for resveratrol to serve as a candidate preventive agent against prostate cancer, but in vivo effects of resveratrol and the mechanisms of action of resveratrol on prostate cancer prevention remain largely unknown. Prostate tumors initially need androgens for growth, but most patients treated with anti-androgen therapy still progress to androgen independence resulting in resistance of the tumors to the therapy and development of hormone-refractory prostate cancer. Wang and coworkers of the Genomic Medicine Institute, Cleveland, USA, concluded that resveratrol may act as potential adjunctive treatment for hormone-refractory prostate cancer [1]. The scientists for the first time demonstrates the mechanism by which the androgen receptor regulates the expression of tumor suppressor gene PTEN at the transcription level, indicating the direct link between a nuclear receptor and the phosphatidylinositol-3-kinase/AKT pathway. Not only the androgen receptor but also the tumor suppressor gene PTEN plays an important role in tumor development and prostate cancer progression. PTEN regulates androgen receptor activity and stability.
A study by the New York Medical College studied the effects of resveratrol in normal prostate epithelial and stromal cells and suggested that resveratrol suppresses cultured prostate stromal proliferation by affecting cell cycle phase distribution and that it targets quinone reductase 2 [2].
Harper and co-workers of the Department of Pharmacology and Toxicology, University of Alabama at Birmingham concluded that resveratrol suppress prostate cancer development in Simian Virus-40 T-antigen rat model, a transgenic model of spontaneously developing prostate cancer [3]. The phytochemical reduced levels of steroid receptor coactivator-3 and growth factor signaling proteins causing reduced cell proliferation and increased apoptosis. Two years earlier the same reasearcher published results of a similar study also using transgenic mice [4] and found that resveratrol in the diet reduced the incidence of poorly differentiated prostatic adenocarcinoma by about 8-fold.
Researchers from at Universidad de Chile, Santiago investigated the effect of resveratrol on the growth of prostate cancer cells and found that the phytochemical dose-dependently induced cytoplasmic retention of NF kappaB mediated by I kappaB alpha [5]. Resveratrol inhibited the binding of NF kappaB to DNA. The concluded that resveratrol could have therapeutic potential for prostate cancer treatment.
[1] Resveratrol regulates the PTEN/AKT pathway through androgen receptor-dependent and -independent mechanisms in prostate cancer cell lines. Hum Mol Genet. 2010 Sep 2.
[2] Uptake of resveratrol and role of resveratrol-targeting protein, quinone reductase 2, in normally cultured human prostate cells. Asian J Androl. 2009 Nov;11(6):653-61.
[3] Genistein and resveratrol, alone and in combination, suppress prostate cancer in SV-40 tag rats. Prostate. 2009 Nov 1;69(15):1668-82.
[4] Resveratrol suppresses prostate cancer progression in transgenic mice. Carcinogenesis. 2007 Sep;28(9):1946-53.
[5] Regulation of cell survival by resveratrol involves inhibition of NF kappa B-regulated gene expression in prostate cancer cells. Prostate. 2009 Jul 1;69(10):1045-54.
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