Apoptosis and anticancer drug resistance.
Anticancer agents induce cancer cell death through apoptosis or necrosis. As anticancer agents at low and high concentrations cause apoptosis and necrosis, respectively, cancer cells may be merely injured by an anticancer agent in apoptosis, and cell death may result from an activation of the internal constituents to induce apoptosis. Therefore, an alternation of apoptotic pathway must change the efficacy of anticancer agents. As an escape of cancer cells from apoptosis seems to be closely associated with the development of anticancer resistance, this report focuses on mechanisms of apoptosis and its association with anticancer resistance. A Bax induces apoptosis mitochondria-dependently, whereas Fas can induce apoptosis mitochondria-independently. An interaction of Bax and Bcl-2 is very important to decide cell life or death, and Bcl-2 phosphorylation may control this interaction: Paclitaxel treatment induced Bcl-2 phosphorylation and typical apoptosis, whereas hyperthermia induced not Bcl-2 phosphorylation but nuclear translocation and failed to induce apoptosis. Moreover, Fas was localized in the cytoplasm of exponentially growing cells and on the cell membrane of confluent cells. We would like to emphasize that it is very important to check the localization of constituents of apoptosis in order to evaluate the susceptibility of cancer cells to apoptosis.
Inoue
S
S
Department of Environmental Medicine and Informatics, Graduate School of Environmental Earth Science, Hokkaido University.
Salah-Eldin
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AE
Omoteyama
K
K
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008928:Mitochondria / Q000502:physiology; D009369:Neoplasms / Q000473:pathology; D009479:Neuropeptides / Q000502:physiology; D017239:Paclitaxel / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; D018631:ras Proteins / Q000502:physiology
D000970:Antineoplastic Agents; C494826:BAX protein, human; C491901:FAS protein, human; D009479:Neuropeptides; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018124:Receptors, Tumor Necrosis Factor; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; D018631:ras Proteins; D017239:Paclitaxel