Journal
ONCOLOGY REPORTS
Volume 22, Issue 2, Pages 385-391Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/or_00000449
Keywords
antimycin A; reactive oxygen species; apoptosis; glutathione; Calu-6
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Funding
- Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, of Korea [A084194]
- Korea Health Promotion Institute [A084194] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Antitnycin A (AMA) inhibits mitochondrial electron transport between cytochrome b and c. We recently demonstrated that AMA inhibits the growth of lung cancer Calu-6 cells and the changes of reactive oxygen species (ROS) and glutathione (GSH) levels affect apoptosis in Calu-6 cells. Here, we examined the effects of N-acetylcysteine (NAC, a well known antioxidant), L-buthionine sulfoximine (BSO, an inhibitor of GSH synthesis), diethyldithiocarbamate (DDC, an inhibitor of Cu, Zn-SOD) or 3-amino-1,2,4-triazole (AT, an inhibitor of catalase) on AMA-treated Calu-6 cells in relation to cell death, ROS and GSH levels. Treatment with AMA induced cell growth inhibition, apoptosis and the loss of mitochondrial membrane potential (MMP) (Delta Psi(m)) in Calu-6 cells. While the intracellular ROS level was decreased in 50 mu M AMA-treated Calu-6 cells, O-2(center dot-) levels among ROS were significantly increased. AMA also induced GSH depletion in Calu-6 cells. Treatment with NAC showed decreasing effect on O-2(center dot-) levels in AMA-treated cells preventing apoptosis, MMP (Delta Psi(m)) loss and GSH depletion in these cells. BSO significantly increased GSH depletion and apoptosis in AMA-treated cells. While both DDC and AT increased ROS levels in AMA-treated Calu-6 cells, only DDC intensified GSH depletion and apoptosis. BSO and AT increased the ROS level in Calu-6 control cells, but these agents did not induce apoptosis and GSH depletion. In conclusion, our results suggest that GSH depletion rather than ROS level in AMA-treated Calu-6 cells is more tightly related to apoptosis.
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