Chemoprevention of Rat Prostate Carcinogenesis by Soy Isoflavones and by Bowman-Birk Inhibitor

Abstract:

Epidemiology studies suggest that soy consumption confers protection against human prostate cancer. To identify the soy component(s) that may be responsible for this chemopreventive activity, studies were conducted to determine the influence of a soy isoflavone mixture (PTI G-2535; 45% genistein, 22% daidzein, 2% glycitein) and a soy-derived protease inhibitor (Bowman-Birk Inhibitor Concentrate; BBIC) on prostate carcinogenesis in rats. Prostate cancers were induced in male Wistar-Unilever rats by a sequential regimen of cyproterone acetate and testosterone propionate, followed by a single intravenous injection of N-methyl-N-nitrosourea (MNU) and chronic androgen stimulation. In separate studies, PTI G-2535 and BBIC were administered continuously at 0 (control), 200, or 2000 mg/kg diet, beginning 1 wk post-MNU. PTI G-2535 and BBIC both conferred modest, but statistically significant and dose-related protection against carcinogenesis in the dorsolateral + anterior prostate. These data demonstrate that both the isoflavone and protein (protease inhibitor) components of soy can inhibit prostate carcinogenesis in the rat. However, the modest individual activities of soy isoflavones and BBIC suggest that while both components may contribute to the chemopreventive activity of soy, combination administration (or exposure to whole soy) may be more effective in prostate cancer prevention than is administration of either component alone.

Acknowledgments and Notes

This work was supported by contract NCI-N01-CN-85177 from the Division of Cancer Prevention, National Cancer Institute, DHHS. The authors thank Leigh Ann Senoussi for assistance in preparation of the manuscript.

Notes

^a : Number of animals considered to be “at risk” for prostate cancer and whose tissues were available for histopathologic evaluation. Excludes deaths prior to 6 mo post-MNU and animals whose tissues were lost to autolysis or cannibalism.

∗ P < 0.05 vs. dietary control.

∗∗ 0.05 < P < 0.10 vs. dietary control.

^a : Number of animals considered to be “at risk” for prostate cancer and whose tissues were available for histopathologic evaluation. Excludes deaths prior to 6 mo post-MNU and animals whose tissues were lost to autolysis or cannibalism.

∗ P = 0.05 vs. dietary control.

∗∗ P < 0.05 for linear trend with increasing BBI dose.