title: Caspases and ROS - dependent mechanism of action mediated by combination of WP 631 and epothilone B.
abstract: In this article, the synergistic effects of WP 631 and epothilone B (Epo B) combination in human ovarian cancer cells (SKOV-3) cells are investigated and the reasons for the exact mechanisms of action of both drugs co-administered are explained. Compared with single drugs, the combination treatment significantly enhances apoptosis as confirmed by increases in caspases (-8, -9, -3) activity, ROS level and DNA damage and decreases in mitochondrial membrane potential. The combination of the compounds activated both caspase - 8 and -9, indicates that both pathways of apoptosis, extrinsic (induced by the effect of Epo B) and intrinsic (triggered mainly by WP 631) participate in the proposed treatment. Thus, the results of this study strongly suggest a synergistic action of the combined treatment with WP 631 and Epo B in SKOV-3 cells death induction.
authors.forename: Aneta
authors.initials: A
authors.lastname: Rogalska
authors.forename: Barbara
authors.initials: B
authors.lastname: Bukowska
authors.affiliation: Department of Thermo biology, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland. aszwar@biol.uni.lodz.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Marczak
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004357:Drug Synergism; D034261:Epothilones / Q000494:pharmacology*; D005260:Female; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010051:Ovarian Neoplasms; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D034261:Epothilones; D017382:Reactive Oxygen Species; C104426:WP 631; D020169:Caspases; C093788:epothilone B; D003630:Daunorubicin