Kaempferol exerts anti-proliferative effects on human ovarian cancer cells by inducing apoptosis, G0/G1 cell cycle arrest and modulation of MEK/ERK and STAT3 pathways

Abstract

Purpose: Ovarian cancer causes significant mortality in women and is one of the most prevalent types of gynaecological cancer world over. Ovarian cancer is often diagnosed at advanced stages and the currently used anticancer drugs produce several adverse effects. Herein, we examined the anticancer effects of a natural flavonoid Kaempferol against a panel of ovarian cancer cells.

Methods: WST-1 and colony formations assays were used to examine the anti-proliferative effects of Kaempferol. AO/EB, DAPI and annexin V/PI staining assays were used to check apoptosis. Cell cycle analysis was performed by flow cytometry and western blotting was used to check the expression of the proteins.

Results: The results showed that Kaempferol could inhibit the growth of ovarian cancer cells with IC50 ranging between 25 to 50 µM. However, the cytotoxic effects of Kaempferol were comparatively negligible against the normal SV40 cells with an IC50 of >120 µM. Exploration of the mechanism of action revealed that Kaempferol exerts growth inhibitory effects on the OVACAR-3 ovarian cancer cells by apoptotic cell death. This was also accompanied with upregulation of apoptotic proteins such as caspase 3, 8 and 9 and Bax. Kaempferol also induced arrest of the OVACAR-3 cells at the G2/M check point of the cell cycle. In addition, Kaempferol could also inhibit the MEK/ERK and STAT3 signal transduction pathways.

Conclusion: Taken together, these results suggest that Kaempferol exerts potent anticancer effects on ovarian cancer cells and may prove useful in the management of ovarian cancer.