Stigmasterol inhibits cancer stem cell activity in endometrial cancer by repressing IGF1R/mTOR/AKT pathway

Endometrial cancer (EC) is a commonly diagnosed gynecological malignancy among women worldwide. Stigmasterol is a potential natural phytosterol present in vegetable oils and seeds with anti-cancer activity. We investigate the effects of stigmasterol on the malignant properties of EC cells and the involved molecular mechanisms. We found that stigmasterol inhibited the proliferation of EC cells according to MTT and colony formation assays. The anti-proliferative effect of stigmasterol was not suppressed by the inhibitors of apoptosis or reactive oxygen species, but was associated with G1 cell cycle arrest. In addition, stigmasterol reduced cell migration by inhibiting vimentin, SNAI1, SLUG, or ZEB1. Stigmasterol also suppressed tumorsphere formation and cancer stemness proteins including β-catenin, c-MYC, and OCT4, as well as the activation of IGF1R/AKT/mTOR pathway activation in EC cells. In conclusion, our study demonstrated that stigmasterol represses cell cycle progression, migration, and cancer stem cell activity in EC cells by inhibiting IGF1R/AKT/mTOR pathway.