Ursolic acid induces apoptosis by suppressing the expression of FoxM1 in MCF-7 human breast cancer cells.

Ursolic acid (UA), a naturally occurring pentacyclic triterpene, is a potent in vitro anticancer agent, acting through control of growth, apoptosis, and differentiation. As the anticancer effect and the mechanism of action of ursolic acid on human breast cancer cells has not been extensively studied, we performed an evaluation of the effects of UA on apoptosis in MCF-7 cells. UA was found to inhibit the proliferation of MCF-7 cells in a concentration and time-dependent manner. After treatment, UA-induced apoptosis was accompanied by a significant decrease in CyclinD1/CDK4 expression, which can be regulated by FoxM1. Previous studies demonstrated that FoxM1 orchestrates the transcription of genes that are essential for cell cycle progression and cell proliferation. The result of Western blot suggested that ursolic acid inhibited the expression of FoxM1. Taken together, the data suggest that the proapoptotic effect of UA on MCF-7 cells is mediated by inhibition of FoxM1 and is highly correlated with inactivation of CyclinD1/CDK4.