Isoflavones are excreted in human urine and can be modulated by soy-rich diets. Recently,
isoflavones were suggested to have protective effects against
bladder cancer cells. We sought to determine the efficacy of the antitumorigenic effects of
isoflavones at concentrations found in the range of human urine excretion and compare normal urothelium and
bladder cancer cells for differential cytotoxicity. A total of seven human
bladder cancer cell lines and an immortalized uroepithelial cell line were used to examine the effects of
genistein,
daidzein, and
biochanin-A, either individually or as an equal-proportion mixture regimen, on cell growth,
DNA synthesis, alterations of cell cycle distribution, and induction of apoptosis. The role of
cyclin B1 and cdc2
kinase in cell cycle arrest was analyzed. In addition, severe combined immunodeficient mice were used to confirm the anti-
cancer effects of
isoflavones in vivo. Cooperative action of
isoflavones was more effective in growth inhibition and apoptosis induction than any single compound.
Genistein tends to cause a dose-dependent induction of G2-M cell cycle arrest and an inhibition of cdc2
kinase activity. However, both
daidzein and
biochanin-A directly induced apoptosis without altering cell cycle distribution. The IC50 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
genistein and combined
isoflavones exhibited a significant
tumor suppressor effect in vivo (P < 0.05). The results justify the potential use of soybean foods as a practical
chemoprevention approach for patients with
urinary tract cancer.