Evaluation of Soy and Black Raspberry Constituents for Prostate Cancer Prevention and Therapy

The preventive and therapeutic effects of soy and black raspberries on prostate cancer are investigated in this dissertation using in vitro and in vivo experimental approaches. We hypothesized that dietary black raspberries could prevent the development of prostate cancer and that black raspberry and soy constituents can enhance the efficacy of taxane chemotherapeutic agents used to treat castration resistant prostate cancer. We show that dietary administration of black raspberries fails to prevent the development of prostate cancer in rats using either a carcinogen- or hormone-induced model of prostate carcinogenesis, and the efficacy of taxane chemotherapy is not affected by dietary administration of either ellagic acid or genistein in a mouse xenograft model. Results from cell culture experiments support our in vivo observations: using several prostate cancer cell lines, we demonstrate that physiologically relevant concentrations of berry and soy constituents do not have significant impact on cell proliferation, migration, mechanisms of drug resistance, or taxane cytotoxicity. We provide the first evidence of a novel mechanism of action by which ellagic acid may inhibit proliferation of cancer cells and we also report inhibitory effects by genistein on a metabolic enzyme involved in drug detoxification. Taken together, our results suggest that low bioavailability of black raspberry and soy compounds following dietary consumption is a highly restrictive factor that limits their use in the prevention and treatment of prostate cancer.