Anti‐metastatic Activity of Dietary Genistein Against Human Prostate Cancer, Using a Unique in Vivo Model

Metastatic spread is the primary cause of mortality from prostate cancer (PCa). Epidemiology studies associate soy-derived genistein consumption to a lower risk of metastatic PCa. We recently reported that in vitro, genistein inhibits metastasis-associated processes of PCa cell detachment, induction of MMP-2, and cell invasion. The objective of this study is to determine in vivo efficacy of genistein on metastasis of human prostate cancer cells. For this, we first developed and characterized a metastatic mouse model using PC-3M PCa cells, wherein orthotopic implants spontaneously metastasized to the lung in 75% of mice, after two weeks. Metastasis was detected and quantified by histomorphometry and immunohistochemical staining for Green Fluorescent protein. This reliable model is unique in that it generates non-saturated metastasis in the lung which is ideal to examine biology and drug efficacy. We, thus, went on to show that genistein consumption significantly reduces metastasis in 100% of mice. This was accompanied by comparable primary PCa growth as seen in mice on control diet, suggesting that genistein suppresses metastasis and not tumorigenesis, at least in this model. Collectively, our findings support that genistein is anti-metastatic, in vivo, against human prostate cancer, and further supports the notion of its therapeutic activity in patients. (This study was supported by a Veteran’s Administration merit grant awarded to RB)