Chemoprevention of Prostate Cancer, HDAC Inhibition and DNA Methylation

Prostate cancer is the most frequently diagnosed non-cutaneous cancer and is the second leading cause of cancer death in American men. The precise etiologic factors that initiate and enhance the progression of prostate cancer remain unknown, but epigenetic alterations and diet/lifestyle factors have come forth as significant contributing factors. Epidemiologic studies suggest that cruciferous vegetable intake decreases the risk for prostate cancer. The long-term goal of this proposal is to identify mechanisms by which dietary compounds, such as those found in cruciferous vegetables decrease prostate cancer risk. The objective of the study is to identify mechanisms by which compounds found in cruciferous vegetables alter gene expression via epigenetic modifications and may prevent prostate cancer development. The investigators have found that SFN, an isothiocyanate found in cruciferous vegetables, inhibits HDAC activity in human colorectal and prostate cancer cells. Targeting the epigenome, including the use of HDAC and DNA methyltransferase (DNMT) inhibitors, is an evolving strategy for cancer chemoprevention and both have shown promise in cancer clinical trials. This Randomized, Double Blind, Clinical Trial will address the following objectives: 1. Identify distribution of SFN and its metabolites and HDAC inhibition following supplementation with an SFN-rich broccoli sprout extract in subjects at risk for prostate cancer (Primary Endpoints) 2. Investigate the effects of supplementation with an SFN-rich broccoli sprout extract on DNA methylation status and proliferation markers in a pre-biopsy setting (secondary analysis) The effects of short-term supplementation with an SFN-rich broccoli sprout extract on benign epithelial tissue will be studied in men characterized as being at risk for prostate cancer in a randomized, placebo-controlled trial. Men scheduled for prostate biopsy will be recruited into the trial. Following successful completion of the consent, two 10 mL blood specimens for study analyses, a 4 mL specimen for total bilirubin assessment will be drawn and the subject will provide a urine sample. The study coordinator will explain the Diet History questionnaires (DHQ) and administer the risk factor and adverse event (AE) questionnaires in order to obtain data on potential confounding dietary variables and gain subjects' baseline symptoms. The study coordinator will provide the subject with a month' supply of either an SFN-rich broccoli sprout extract (BSE) capsule which consist of 200µmol of sulforaphane (SFN) or matching placebo, as dispensed by the Research Pharmacy. The matching placebo for the BSE consists of a gelatin capsule containing microcrystalline cellulose. Around every 2 weeks, study coordinator will call to complete AE reporting and any changes in medications or supplements and complete brief cruciferous vegetable intake checklist. Subjects will return any unused study "drug" to the study coordinator at the time of biopsy (or at the 4 week visit if subject's prostate biopsy is delayed).