The overall goal of this proposal is to use a novel in vivo human intervention model to understand the activities of sulforaphane (the bioactive compound in Brassica vegetables) in human prostate since these bioactive plant compounds are believed to be associated with prostate cancer risk. Several large, well-designed epidemiological studies have found that regular consumption of vegetables in the Brassica oleracea (Cruciferae) family is associated with reduced prostate cancer risk. Further, there is ample evidence from in vitro and experimental animal studies, along with a limited number of human feeding studies, that metabolites of the these compounds induce phase II detoxification enzymes, decrease cancer growth, and modulate oxidative stress. However, the in vivo effects of the bioactive compounds in Brassica vegetables on human prostate are unknown. Here we propose a randomized, double-blinded, placebo-controlled clinical trial to evaluate the in vivo effects of a high-sulforaphane, broccoli sprout extract on human prostate tissue. We will randomize 100 men with localized, low-grade prostate cancer, and use prostate tissue collected at both the time of diagnosis (biopsy) and prostatectomy to assess carefully selected and evaluated measures of phase II detoxifying enzyme induction, intra-prostatic steroid hormone metabolism, oxidative damage, and growth of prostate cancer cells. The Primary Specific Aims are to test whether the broccoli sprout extract: (1) induces an antioxidant response and reduces oxidative damage in human prostate and (2) increases DHT catabolism and reduces intra-prostatic dihydrotestosterone (DHT) concentration. Secondary Aims will examine: (1) whether the high-sulforaphane broccoli sprout extract affects pathways associated with development and/or early progression of prostate cancer and (2) whether GSTM1 genotype modifies responses to the high- sulforaphane broccoli sprout extract. We hope to confirm in humans the findings from studies examining sulforaphane in animal and in vitro models, which would be an important advance in our work toward the dietary prevention of prostate cancer. We believe it is likely that sulforaphane could be an effective preventive agent for prostate cancer, and that research to evaluate the effects of Brassica compounds in humans is well motivated.
Prostate cancer is the most commonly diagnosed cancer among men as well as the second leading cause of male cancer deaths in the United States. Dietary change interventions, or use of bioactive compounds derived from food, are an especially appealing approach to prostate cancer prevention due to their low cost, low toxicity, and absence of adverse events. Before public health recommendations for prostate cancer can be offered to men, a better understanding of the potential mechanisms, as well as efficacy of the agents is needed. This randomized trial of bioactive compounds in broccoli may provide an important, cost-effective, low-adverse-event means of prevention of the most common cancer in US males.
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