Embelin is an active ingredient of traditional herbal medicine that exhibits cytotoxic effect and inhibits cell proliferation in various cancer cell types. It is a small molecular inhibitor of XIAP undergoing preclinical testing for its anticancer effects in many different cancer types. In this study we have investigated its role as a chemotherapeutic agent in a panel of ovarian cancer cell lines. Utilising the MTT assay and annexin staining we demonstrate that embelin exhibits a potent, dose dependent cytotoxic effect in human ovarian cancer cells. Surprisingly in contrast to the previously reported cytotoxicity of embelin in many other cancer cell types, treatment of ovarian cancer cells with embelin promoted autophagy and not apoptosis as evidenced by the death without caspase 3 activation and induces cellular swelling and cytoplasmic vacuolization with evident features of necrotic cell death. Treatment of ovarian cancer cells with embelin demonsrnstrated autophagic hallmarks, including an increased number of autophagosomes were observed through acridine orange staining. Embelin also induced cell autophagy, as demonstrated by the punctuate distribution of GFP-LC3, as well as the LC3 cleavage and beclin1 activation. Red green fluorescence in acridine orange stained cells by flowcyometry further confirmed the autophagy action by embelin treatment. Our findings demonstrate a new death pathway underlying the cytotoxic effect of embelin, but also suggest that targeting autophagy could augment the anticancer activity, providing the framework for further development of embelin as a new chemotherapeutic agent for ovarian cancer treatment.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2265. doi:1538-7445.AM2012-2265