Prevention of spontaneous prostate-related cancer in Lobund-Wistar rats by a soy protein isolate/isoflavone diet.

Abstract

Epidemiological surveys recorded that men in the Orient (Japan and China) consuming diets high in soy food were at low risk of developing clinical prostate cancer, compared to a relatively high risk among men in the West who consumed diets low in soy food. Soybeans contain phytoestrogens (isoflavones) with many recorded anticancer mechanisms. The Lobund-Wistar (L-W) rat is a unique model system: approximately 30% develop metastasizing adenocarcinomas spontaneously in the anterior prostate-seminal vesicle complex (P-SV), from which the tumors expand into the dorsolateral lobes. L-W rats are inherently predisposed, possibly by unusually high levels of circulating testosterone (T), to develop P-SV tumors which are T-dependent in the early stages and T-independent in advanced stages of tumorigenesis. L-W rats were fed two diets from age 2-24 months: 1) natural ingredient diet L-485 (Harlan TekLad Diets, Madison, WI) containing soy meal, or 2) a modified starch-casein diet in which soy protein isolate/isoflavones (SPII) replaced casein as a source of protein. At age 24 months, 3 of 99 (3%) rats on diet SPII and 30 of 100 (30%) rats on diet L-485 developed spontaneous P-SV cancers. Rats on the SPII diet manifested a significant reduction of circulating T, approaching physiological levels. Failure of the rats on diet L-485 to prevent P-SV cancer development suggests that soy meal contained a factor(s) that blocked the antiandrogenic action of the phytoestrogen. The spontaneous development of P-SV cancers was significantly prevented in L-W rats consuming the SPII diet from age 2-24 months, possibly through an agonist effect of the soy-derived phytoestrogens.