Inhibition of cell growth and induction of apoptosis in ovarian carcinoma cell lines CaOV3 and SKOV3 by natural withanolide Withaferin A

Objective: Withaferin A, a natural withanolide, has shown anti-cancer properties in various cancers including breast Cancer, but its effects in ovarian Cancer remain unexplored. Notch 1 and Notch3 are critically involved in ovarian Cancer progression. We decided to examine the effects of Withaferin A in ovarian carcinoma cell lines and its molecular mechanism of action including its regulation of Notch.

Methods: The effects of Withaferin A were examined in CaOV3 and SKOV3 ovarian carcinoma cell lines using MTS assay, clonogenic assay, annexin V/propidium iodide flow cytometry, and cell cycle analysis. Western analysis was conducted to examine the molecular mechanisms of action.

Results: Withaferin A inhibited the growth and colony formation of CaOV3 and SKOV3 cells by inducing Apoptosis and cell cycle arrest. These changes correlated with down-regulation of Notch1, Notch3, cdc25C, total and phosphorylated Akt, and Bcl-2 proteins.

Conclusions: Withaferin A inhibits CaOV3 and SKOV3 ovarian carcinoma cell growth, at least in part by targeting Notch1 and Notch3.