Abstract 1766: Effect of soy isoflavones on prostate cancer cell cycle regulation and apoptosis

Background: As many as one-third of all cancer deaths in the United States can be linked to diet. Significant epidemiological evidence suggests a role of a variety of dietary factors including the amount of dietary soy. In Asian countries where the average diet consists of 10 times the amount of soy products consumed compared to the average American diet there is a significantly lower incidence of prostate and breast cancer. Further supporting a dietary and environmental influence is the finding that Asian immigrants who have moved to the United States and adopt a Western diet have a prostate cancer incidence that approaches U.S. born males. These findings have been supported by other studies and, again, suggest that environmental factors such as dietary soy intake may be responsible for these differences in geographic incidence. Although there is this preclinical and epidemiological data suggesting that soy isoflavones decrease the risk of developing prostate cancer (PC), there is limited information regarding the in vivo effects of soy supplementation on human PC and benign prostate tissue. Methods: The primary objective of this study was to evaluate the molecular effects of soy isoflavones on human PC cell cycle regulation and apoptosis. Patients with histologically confirmed PC who had chosen radical prostatectomy (RRP) for treatment (without any other primary therapy) were randomized in double blind fashion to receive either soy supplementation or placebo. The patients in the treatment group received 4 capsules of a commercially available pure soy tablet (240 mg of total isoflavones) from time of enrollment until RRP. At the time of surgery, fresh tissue was collected from the tumor and adjacent normal tissue. Using these samples, we evaluated the status of genes essential for cell cycle regulation and apoptosis using cDNA microarray analyses. Results: In this preliminary analysis, multiple cell cycle and apoptotic genes were either down regulated or up regulated in the treatment samples compared to the placebo treated samples, including BAX, BCL-2, and Caspase-7. This effect was present in both tumor and adjacent normal tissue. Using samples from an additional four patients, we then further characterized these changes in gene expression using Western Blots analysis. Cleaved caspase-7 was up regulated in soy treated tumor and adjacent normal samples when compared to placebo, suggesting that soy mediates apoptosis though Caspace-7. The expression of BCL2L1 was down regulated in the treated compared to placebo tissue with this change being most marked in the adjacent normal samples. Conclusion: In total, our results suggest that soy isoflavones may exert a prostate cancer protective effect via a beneficial effect on cell cycle regulation and apoptosis.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1766.