title: Analysis of epothilone B-induced cell death in normal ovarian cells.
abstract: We have investigated the mode of cell death induced by a new microtubule-stabilizing agent, epothilone B (EpoB, patupilone), and a clinically used medicine, paclitaxel (PTX), in normal ovarian cells. Using fluorescence microscopy, polyacrylamide gel electrophoresis preceding Western blot analysis, as well as spectrofluorimetric and colorimetric detection, we demonstrate that, compared to EpoB, PTX induced high time-dependent morphological and biochemical changes typical of apoptosis. Induction of apoptosis followed an early increase in p53 levels. Apoptosis reached its maximum at 24-48 h. At the same time, there was a significant increase in caspase-9 and -3 activity and PARP fragmentation, which suggests that an intrinsic path was involved. Apoptosis in MM14 cells was increased more by PTX than EpoB, and also induced more necrosis responsible for inflammation (1.4-fold) than EpoB.
authors: Department of Thermobiology, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236, Lodz, Poland.
authors: Aneta
authors: A
authors: Rogalska
authors: Arkadiusz
authors: A
authors: Gajek
authors: Agnieszka
authors: A
authors: Marczak
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002460:Cell Line; D034261:Epothilones / Q000494:pharmacology*; D005260:Female; D051379:Mice; D008856:Microscopy, Fluorescence; D010053:Ovary / Q000166:cytology / Q000187:drug effects*; D017239:Paclitaxel / Q000633:toxicity; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D034261:Epothilones; D016159:Tumor Suppressor Protein p53; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D053453:Caspase 9; D017239:Paclitaxel; C093788:epothilone B
keywords: PARP; apoptosis; caspases; epothilone B; paclitaxel