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Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Caspases and ROS - Dependent Mechanism of Action Mediated by Combination of WP 631 and Epothilone B

Author(s): Aneta Rogalska, Barbara Bukowska and Agnieszka Marczak

Volume 14, Issue 9, 2014

Page: [1261 - 1270] Pages: 10

DOI: 10.2174/1871520614666140608150807

Price: $65

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.

Keywords: Apoptosis, epothilone B, ovarian cancer, synergism, WP 631.

Graphical Abstract

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