Suppression of arsenic trioxide-induced apoptosis in HeLa cells by N-acetylcysteine.
Arsenic trioxide (ATO) can affect many biological functions such as apoptosis and differentiation in various cells. We investigated the involvement of ROS and GSH in ATO-induced HeLa cell death using ROS scavengers, especially N-acetylcysteine (NAC). ATO increased intracellular O(2)(*-) levels and reduced intracellular GSH content. The ROS scavengers, Tempol, Tiron and Trimetazidine, did not significantly reduce levels of ROS or GSH depletion in ATO-treated HeLa cells. Nor did they reduce the apoptosis induced by ATO. In contrast, treatment with NAC reduced ROS levels and GSH depletion in the ATO-treated HeLa cells and prevented ATO-induced apoptosis. Treatment with exogenous SOD and catalase reduced the depletion of GSH content in ATO-treated cells. Catalase strongly protected the cells from ATO-induced apoptosis. In addition, treatment with SOD, catalase and NAC slightly inhibited the G1 phase accumulation induced by ATO. In conclusion, NAC protects HeLa cells from apoptosis induced by ATO by up-regulating intracellular GSH content and partially reducing the production of O(2)(*-).
Department of Physiology, Medical School, Institute for Medical Sciences, Center for Healthcare Technology Development, Chonbuk National University, Jeonju 561-180, Korea.
Yong Hwan
YH
Han
Sung Zoo
SZ
Kim
Suhn Hee
SH
Kim
Woo Hyun
WH
Park
D000111:Acetylcysteine / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006131:Growth Inhibitors / Q000494:pharmacology; D006367:HeLa Cells / Q000473:pathology; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010087:Oxides / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D000970:Antineoplastic Agents; D001152:Arsenicals; D016166:Free Radical Scavengers; D006131:Growth Inhibitors; D010087:Oxides; D017382:Reactive Oxygen Species; D013481:Superoxides; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D000077237:Arsenic Trioxide; D000111:Acetylcysteine