WP 631 and Epo B synergize in SKOV-3 human ovarian cancer cells

Abstract

Combined therapy is one of the basic methods of treatment different types of cancer. It allows to reduce the side effects of each component while maximizing the therapeutic action. The aim of this study was to evaluate the impact of two new drugs: WP 631 (bisanthracycline) and epothilone B (Epo B), added in combination on the SKOV-3 human ovarian cancer cells. To assess the type of interaction between WP 631 and Epo B isobolografic analysis was applied based on the cytotoxicity of drugs determined by the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolinum bromide) assay. Apoptotic and necrotic cell levels were measured by double staining with Hoechst 33258 and propidium iodide, Annexin V-FITC staining and by using TUNEL assay. The combination of WP 631 and Epo B is more potent than drugs added alone. The quantitative analysis indicated that the major mode of cell death induced by the combination after 72 h treatment was early apoptosis, whereas drugs administered alone generated less intensive apoptosis. The present report demonstrates for the first time that WP 631 and Epo B co-administered synergize in SKOV-3 cell line (Z(ex)/Z(th)<1).

Keywords: Apoptosis; Epothilone B; Isobolograms; Ovarian cancer; Synergism; WP 631.