3903

Bladder cancer is the fifth most common malignancy diagnosed in the United States. A role of diet and nutrition in bladder carcinogenesis and anti-carcinogenesis is biologically plausible since most substances or metabolites are excreted through the urinary tract, and are consequently in direct contact with the mucosa of the bladder. With the unknown etiological factors for bladder cancer carcinogenesis and the fact that bladder cancer patients are facing both threat of metastases and uncontrolled local recurrence after treatment, additional efforts to define dietary intervention or chemoprevention programs for bladder cancer progression/recurrence and metastasis are urgently needed. Genistein, one of the derivatives of soy isoflavone, is suggested to be a chemo preventive agent against various type of cancer in human. We thus hypothesize that soy bioactive components, especially soy isoflavone genistein, may inhibit proliferation of bladder cancer cells. We determined anti-growth activity of genistein against well-differentiated RT-4 and poorly differentiated 253J B-V human bladder cancer cells in vitro. We observed that genistein inhibited the growth of both cell lines in a time- and dose-dependent manner. Cell cycle progression analysis indicated that genistein inhibited proliferation by G2/M arrest and induced apoptosis. In a pilot animal study, male SCID mice were pretreated with the control, genistin (0.14%) or the genistein-rich soy phytochemical concentrate (SPC, 0.5%) diet for three weeks before intrabladder implantation of 253J B-V cells, and continued dietary treatment throughout the experiment. Food intake and body weight were measured weekly. The experiment was finished 12 weeks after tumor cell implantation. Mice treated with genistin and SPC had reduced final tumor weights by 74% (P<0.05) and 57% (P>0.05), respectively, compared with the control. Biomarker analyses indicated that the inhibitory effects of genistin and SPC were associated with inhibition of tumor cell proliferation and induction of tumor cell apoptosis, and inhibition of tumor angiogenesis in vivo. Our results suggest that further research on the role of soy bioactive components may play in bladder cancer prevention is warranted. The authors thanks Dr. P. N. Dinney from MD Anderson Cancer Center for providing the 253J B-V cell line and NIH/NCI (RO1 CA92546) for funding support.

[Proc Amer Assoc Cancer Res, Volume 45, 2004]