DIETARY SOY ISOFLAVONES AND PROSTATE CANCER PROGRESSION

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The objective of this proposal is to investigate the preventive role of soy isoflavones in prostate cancer (PCA) progression and angiogenesis. The specific aims are: l) to study the effects of soy isoflavones on inhibiting expression of membrane-type metalloproteinase (MT-MMP) by PCA cells, fibroblasts, or endothelial cells (ECs) in vitro, and 2) to determine if diets containing soy protein isolate (SPI) or purified isoflavones inhibit prostate tumor progression, angiogenesis, and MT-MMP expression in vivo. Human PCA cells (PC-3, DU 145, and LNCAP), fibroblasts, and ECs will be treated with isoflavones. MMPs-containing conditioned media and MT-MMP-containing plasma membranes will be prepared. RNase protection assays, Western blotting, and zymography will be applied to determine mRNA, protein, and activity of MT-MMP to test the hypothesis that isoflavones inhibit PCA progression, and prostate tumor angiogenesis by inhibiting MT-MMP expression by PCA and fibroblasts, and ECs, respectively. In animal study, human PCA cell-inoculated nude mice will be fed control, SPI-based, or isoflavone-supplemented diets. Tumor sizes will be measured, and tumors removed for determinations of MT-MMP mRNA, protein and activity to evaluate the effects of isoflavones on in vivo inhibition of PCA progression. Anti-angiogenic effect of isoflavones will be evaluated by immunohistochemical analysis of microvessels.