Dietary soy is widely marketed and used as both complementary and alternative therapy for the prevention and treatment of chronic diseases. Dietary derived soy isoflavonoids have anticancer activities in vitro and in animal models, and these isoflavones or are found in serum in high concentrations after ingestion of a soy-rich meal. Furthermore, these isoflavones concentrate in prostatic tissue, and may have selective activity in the prostate because of their affinity for estrogen receptor beta, which is abundant in prostatic epithelium. Recent findings in our laboratories and by our collaborators indicate potential for therapeutic benefit in normal and neoplastic prostate. The goal of this translational application is to determine whether a dietary supplement consisting of whole soy protein can inhibit the proliferation of prostate cancer cells in human patients. This question will be tested in a clinical therapeutic intervention in men with prostate cancer. We hypothesize that dietary soy consumption will decrease proliferation in neoplastic and adjacent normal prostatic tissues, as reflected in elevated expression of cell cycle inhibitory proteins (p27 and p21), increased apoptosis, and decreased expression of proliferation markers (KI67-MIB and cyclin B1). In order to obtain preliminary data to support or refute this hypothesis in preparation for a future R01 submission, we intend to use an intervention with 25 grams of dietary soy providing approximately 100 mg of isoflavones in a pre-prostatectomy design to assess whether or not there is a short-term effect of soy on tissue biomarkers of proliferation and signaling. We will also test whether this short-term intervention alters serum PSA concentrations between the time of biopsy and prostatectomy. We believe that the data obtained via the work proposed herein will provide valuable preliminary data for further institutional development of the preprostatectomy model for testing of future complementary and alternative interventions.
