BERKELEY, CA (UroToday.com) - Soy isoflavones are dietary components for which an association has been demonstrated with reduced risk of prostate cancer, mostly in Asian populations. However, the exact mechanism by which these isoflavones may prevent the development or progression of prostate cancer is not completely understood. There are a growing number of animal and in vitro studies that have attempted to elucidate these mechanisms. The predominant and most biologically active isoflavones in soy products, genistein, daidzein, equol, and glycetin, inhibit prostate carcinogenesis in some animal models. Cell-based studies show that soy isoflavones regulate genes that control cell cycle and apoptosis.
In this review, we discussed the literature relevant to the molecular events that may account for the benefit of soy isoflavones in prostate cancer prevention or treatment. These reports show that although soy isoflavone-induced growth arrest and apoptosis of prostate cancer cells are plausible mechanisms, other chemo-protective mechanisms are also worthy of consideration. These potential mechanisms include antioxidant defenses, DNA repair processes, inhibition of angiogenesis and metastasis, potentiation of radiotherapy and chemotherapeutic agents, and antagonism of estrogen and androgen receptor-mediated signaling pathways. Moreover, other cells in the cancer milieu, such as the stromal fibroblastic cells, endothelial cells, and immune cells, may be targeted by soy isoflavones, which may contribute to soy-mediated prostate cancer prevention.
We described and discussed these mechanisms in some detail along with considerations about the doses and the preclinical models that have been used to study them. Cell-based models are limited to study of treatment of prostate cancer with soy-derived agents. Some of these cell-based studies have shown that isoflavones compounds such as genistein, at physiological concentrations, can increase rather than inhibit cell proliferation of prostate cancer cells that have certain androgen receptor mutations, inducing potentially harmful effects (PLOS One Oct 22, 2013;8(10):e78479).
Moreover, the preventive effects of dietary soy against prostate cancer development have been reported in animal models. Although the results of most of these animal studies indicate that soy can prevent the development of this malignancy, a great discrepancy was found among clinical trials. Our data showed that a two-year daily administered soy supplement did not reduce the risk of recurrence in men following radical prostatectomy (JAMA 2013;310(2):170-178). It is possible that short-term soy consumption is insufficient to modify risk of prostate cancer and that life-long exposure to soy is needed to prevent this disease, which would be consistent with the modestly reduced risk found for soy consumption in epidemiologic studies.
Written by:
Abeer M. Mahmoud, MD, PhD and Maarten Bosland, DVSc, PhD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Department of Pathology, University of Illinois at Chicago, Chicago, IL USA
Soy isoflavones and prostate cancer: A review of molecular mechanisms - Abstract
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