title: 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.
authors.affiliation: Department of Thermobiology, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland. Electronic address: zychan@biol.uni.lodz.pl.
authors.forename: Aneta
authors.initials: A
authors.lastname: Rogalska
authors.affiliation: Department of Thermobiology, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Szula
authors.affiliation: Department of Thermobiology, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Gajek
authors.affiliation: Department of Thermobiology, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Marczak
authors.affiliation: Department of Thermobiology, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.
authors.forename: Zofia
authors.initials: Z
authors.lastname: Jóźwiak
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D034261:Epothilones / Q000494:pharmacology* / Q000633:toxicity; D005260:Female; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D050257:Tubulin Modulators / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D034261:Epothilones; D017382:Reactive Oxygen Species; D050257:Tubulin Modulators; D045304:Cytochromes c; D017239:Paclitaxel; D002118:Calcium; C093788:epothilone B
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