Daidzein exerts anti-tumor activity against bladder cancer cells via inhibition of FGFR3 pathway

Bladder cancer is one of the causes of cancer-related death and has a high mortality rate. Daidzein, a natural isoflavone compound predominantly extracted from soybeans, has been reported to exhibit several bioactivities, including anti-tumor. However, the effects of daidzein on bladder cancer remains unrevealed. Here we investigated the effects and molecular mechanisms of daidzein on bladder cancer using multiple in vitro cell lines and in vivo xenograft mice studies. Our results showed that daidzein reduced cell viability in a time- and concentration-dependent manner. Daidzein significantly impaired colony formation, caused Gl/S cell cycle arrest and induced apoptosis of the bladder cancer cells. We also verified that daidzein efficiently suppressed RT112 cell xenograft tumor growth in nude mice. Mechanism studies indicated that significant down-regulation of the FGFR3 signaling pathway was responsible for the efficacy of daidzein. The phosphorylation levels of FGFR3, Akt and Erk proteins were suppressed in association with the decreasing of some apoptosis-suppressing molecules under the daidzein treatment. Knockdown of endogenous FGFR3 impaired the activity of daidzein against bladder cancer, which suggested that the effect of daidzein was mainly mediated by FGFR3 pathway. In addition, the function model of daidzein was similar with FGFR3 antagonist PD173074 in RT112 cells. Taken together, the results this study demonstrate that daidzein is capable of inhibiting bladder cancer growth and might be a novel effective chemotherapeutic agent for the application to combat bladder carcinoma.