The potential of soybean foods as a chemoprevention approach for human urinary tract cancer

Isoflavones are excreted in human urine and can be modulated by soy-rich di ets. Recently, isoflavones were suggested to have protective effects agains t bladder cancer cells. We sought to determine the efficacy of the antitumo rigenic effects of isoflavones at concentrations found in the range of huma n urine excretion and compare normal urothelium and bladder cancer cells fo r differential cytotoxicity, A total of seven human bladder cancer cell lin es and an immortalized uroepithelial cell line were used to examine the eff ects of genistein, daidzein, and biochanin-A, either individually or as an equal-proportion mixture regimen, on cell growth, DNA synthesis, alteration s of cell cycle distribution, and induction of apoptosis. The role of cycli n B1 and cdc2 kinase in cell cycle arrest was analyzed. In addition, severe combined immunodeficient mice were used to confirm the anticancer effects of isoflavones in vivo. Cooperative action of isoflavones was more effectiv e in growth inhibition and apoptosis induction than any single compound. Ge nistein tends to cause a dose-dependent induction of G(2)-M cell cycle arre st and an inhibition of cdc2 kinase activity. However, both daidzein and bi ochanin-A directly induced apoptosis without altering cell cycle distributi on. The IC,, values in non-transformed cells were higher than those in most cancer cell lines, and the IC50 of the mixture regimen was within reach of the levels observed in urine after a soy challenge. Furthermore, both geni stein and combined isoflavones exhibited a significant tumor suppressor eff ect in vivo (P < 0.05), The results justify the potential use of soybean fo ods as a practical chemoprevention approach for patients with urinary tract cancer.