Tiron, a ROS scavenger, protects human lung cancer Calu-6 cells against antimycin A-induced cell death.
Antimycin A (AMA) inhibits the mitochondrial electron transport between cytochromes b and c. However, the relationship between AMA and lung cancer cells is poorly understood. In this study, we investigated the involvement of reactive oxygen species (ROS) and glutathione (GSH) in AMA-treated lung cancer Calu-6 cell death. Treatment with AMA reduced cell viability in a dose-dependent manner for 72 h. The intracellular ROS levels were decreased in Calu-6 cells treated with low doses of AMA (10, 25 or 50 microM) at 72 h. However, the levels increased in cells treated with a high dose of 100 microM AMA. Levels of O2.- were significantly increased in AMA-treated cells at 72 h. The increases in ROS levels including O2.- in AMA-treated cells were observed within 10 min. Treatment with AMA reduced the intracellular GSH content. SOD activity was up-regulated in AMA-treated Calu-6 cells at 72 h. However, catalase activity was down-regulated by AMA. Treatment with tiron, a ROS scavenger, reduced the intracellular ROS levels, which were associated with a partial reduction of apoptosis. Treatment with exogenous SOD and catalase significantly inhibited loss of the mitochondrial transmembrane potential (DeltaPsim) in AMA-treated Calu-6 cells. In conclusion, our results suggest that the changes of intracellular ROS and GSH affect apoptosis in AMA-treated Calu-6 cells.
Han
Yong Hwan
YH
Department of Physiology, Medical School, Institute for Medical Sciences, Chonbuk National University, JeonJu 561-180, Korea.
Park
Woo Hyun
WH
D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000494:pharmacology*; D000968:Antimycin A / Q000031:analogs & derivatives* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002374:Catalase / Q000378:metabolism; D045744:Cell Line, Tumor; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005978:Glutathione / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase / Q000378:metabolism
D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; C032456:antimycin; D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; D000968:Antimycin A; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione