Kaempferol, a natural dietary flavonoid, suppresses 17β-estradiol-induced survivin expression and causes apoptotic cell death in endometrial cancer.

Abstract

Endometrioid endometrial carcinoma, commonly known as type 1 endometrial cancer, accounts for >80% of endometrial carcinomas and is dependent on estrogen. We recently reported on the prognostic significance of the BIRC5 survivin gene in endometrial cancer. Estradiol induces survivin expression in estrogen receptor-positive, but not in estrogen receptor-negative, cancer cells. Kaempferol, a bioflavonoid, reportedly inhibits estrogen receptor-α (ERα) in hormone receptor-positive breast cancer cells. However, whether kaempferol-mediated inhibition of ERα suppresses survivin and induces cell death in endometrial cancer remains unclarified. The present study evaluated the antitumor effects of kaempferol on endometrial cancer cells. Cell viability assays, flow cytometry analysis, western blotting and annexin V analyses were used to analyze the antitumor effects of kaempferol. The results demonstrated that kaempferol successfully suppressed the viability of two ER-positive endometrial cancer cell lines, with IC50 values of 83 and 65 µM. In addition, kaempferol induced sub-G1 cell accumulation and apoptotic cell death (P<0.01) in a dose-dependent manner. Treatment of cells with estradiol significantly induced co-expression of nuclear ERα and survivin proteins (P<0.001). Further evaluation revealed that kaempferol causes apoptotic cell death largely by suppressing ERα, survivin and Bcl-2 protein. Therefore, the results of the present study suggested that targeting ERα and survivin with kaempferol may be a novel therapeutic option against endometrial carcinoma.