A role of dietary bioactive components in
bladder cancer prevention is biologically plausible because most substances or metabolites are excreted through the urinary tract and are consequently in direct contact with the mucosa of the bladder. We first determined antigrowth activity of
genistein against poorly differentiated 253J B-V human
bladder cancer cells in vitro.
Genistein inhibited the cell growth in a time- and dose-dependent manner via G(2)-M arrest, down-regulation of
nuclear factor kappaB (
NF-kappaB), and induction of apoptosis. We also evaluated both
genistin, which is a natural form of
genistein, and the
isoflavone-rich soy
phytochemical concentrate (SPC) on the growth and
metastasis of 253J B-V
tumors in an orthotopic
tumor model. Mice treated with
genistin and SPC had reduced final
tumor weights by 56% (P < 0.05) and 52% (P < 0.05), respectively, associated with induction of
tumor cell apoptosis and inhibition of
tumor angiogenesis in vivo. In addition, SPC treatment, but not
genistin treatment, significantly inhibited lung
metastases by 95% (P < 0.01) associated with significant down-regulation of
NF-kappaB expression in
tumor tissues and reduction of circulating
insulin-like growth factor-I levels, suggesting that SPC may contain other bioactive ingredients that have antimetastatic activity. The results from our studies suggest that further clinical investigation should be warranted to apply soy
phytochemicals, such as SPC, as a potent prevention regimen for
bladder cancer progression. This orthotopic human
bladder tumor model also provides a clinically relevant experimental tool for assessing potential preventive activity of other dietary components against
bladder tumor growth and
metastasis.