Activation of apoptotic pathway in normal, cancer ovarian cells by epothilone B

Abstract

The epothilones, a new class of microtubule-targeting agents, seem to be a very promising alternative to the current strategy of cancer treatment. We have analyzed the aspects of epothilone B (Epo B) on cellular metabolism of tumor (OV-90) and normal (MM 14) ovarian cells. The observed effects were compared with those of paclitaxel (PTX), which is now a standard for the treatment of ovarian cancer. The results provide direct evidence that Epo B is considerably more cytotoxic to human OV-90 ovarian cancer cells than PTX. We have found, that antitumor efficacy of this new drug is related to its apoptosis-inducing ability, which was confirmed during measurements typical markers of the process. Epo B induced changes in morphology of cells, mitochondrial membrane potential and cytochrome c release. Also a slight increase of the intracellular calcium level was observed. Moreover, we have found that ROS production, stimulated by Epo B, is directly involved in the induction of apoptosis via mitochondrial pathway.

Keywords: 2′,7′-dichlorodihydrofluorescein diacetate; 5,5′6,6′-tetrachloro-1,1′3,3′-tetraethyl-benzimidazol-carbocyanine iodide; Apoptosis; DCFH(2)-DA; Epo B; Epothilone B; Human ovarian cell lines; JC-1; PTX; Paclitaxel; epothilone B; paclitaxel.