N-acetyl cysteine and caffeic acid phenethyl ester sensitize astrocytoma cells to Fas-mediated cell death in a redox-dependent manner.
In this study, we investigated the role of reactive oxygen species (ROS) in Fas-induced cell death in human astrocytoma cells. Fas activation increased intracellular ROS levels in a NADPH oxidase- and caspase-dependent manner. ROS inhibitors such as N-acetyl cysteine (NAC) and caffeic acid phenethyl ester (CAPE) dramatically sensitized astocytoma cells to Fas-induced loss of mitochondrial transmembrane potential and subsequent cell death, which were abrogated by pretreatment with z-VAD-fmk, a broad-spectrum caspase inhibitor. These results collectively indicate that NAC and CAPE sensitize astrocytoma cells to Fas-induced apoptosis in a redox-dependent manner, suggesting a potential use in the treatment of malignant brain tumors.
Choi
Kyungsun
K
Laboratory of Computational Cell Biology, Department of Brain and Bioengineering, Korea Advanced Institute of Science and Technology, Yuseong-gu, Daejeon 305-701, Republic of Korea.
Han
Young-Hee
YH
Choi
Chulhee
C
D000111:Acetylcysteine / Q000494:pharmacology*; D001254:Astrocytoma / Q000188:drug therapy* / Q000473:pathology; D002109:Caffeic Acids / Q000494:pharmacology*; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008564:Membrane Potentials; D051336:Mitochondrial Membranes / Q000378:metabolism; D008954:Models, Biological; D010084:Oxidation-Reduction; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D017382:Reactive Oxygen Species; D013997:Time Factors; D019014:fas Receptor / Q000378:metabolism*
D002109:Caffeic Acids; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D019014:fas Receptor; D020169:Caspases; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol; D000111:Acetylcysteine