Antitumor agent-induced apoptosis in myeloid leukemia cells: a controlled suicide.
Traditional antitumor research has generally believed that the cytotoxicity of antitumor agents was directly correlated with the amount of drug-induced cellular lesions. Accordingly, oncologists have tried to improve anticancer agent/target interactions by increasing the intracellular dose of active effectors. However, a growing body of evidence stemming from both clinical and experimental observations, strongly suggests that similar anticancer-induced lesions may result in different cellular responses, greatly influencing cytotoxicity. For example, it has been shown that in some but not all cellular models, antitumor agents trigger apoptosis, an irreversible process which leads to a rapid and complete elimination of tumor cells. Several of these studies also demonstrated that apoptosis induced by antitumor agents is highly regulated by multiple signaling pathways which are themselves influenced by oncogenes, protein kinase activities, external stimuli and the oxidative balance. Therefore, it appears that cell death commitment is controlled by both external and internal factors which interfere downstream of drug- or ionizing radiation-target interaction. The characterization of these mediators may provide novel strategies for modulating intracellular signaling pathways in order to promote apoptosis in drug-resistant tumor cells.
Jaffrézou
J P
JP
CJF INSERM 9503, Centre Claudius Régaud, Toulouse, France. jaffrezou@regaud-tlse.fnclcc.fr
Bettaïeb
A
A
Levade
T
T
Laurent
G
G
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D016158:Genes, p53; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics / Q000473:pathology*; D008954:Models, Biological; D009336:Necrosis; D009363:Neoplasm Proteins / Q000502:physiology; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D009857:Oncogenes; D018384:Oxidative Stress; D015398:Signal Transduction; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D009363:Neoplasm Proteins; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors