Han Yong Hwan, Park Woo Hyun
Department of Physiology, Medical School, Institute for Medical Sciences, Chonbuk National University, JeonJu 561-180, Korea.
Oncol Rep. 2009 Jan;21(1):253-61.
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.
抗霉素A（AMA）抑制细胞色素b和c之间的线粒体电子传递。然而，AMA与肺癌细胞之间的关系却鲜为人知。在本研究中，我们调查了活性氧（ROS）和谷胱甘肽（GSH）在AMA处理的肺癌Calu-6细胞死亡中的作用。AMA处理72小时后，细胞活力呈剂量依赖性降低。低剂量AMA（10、25或50微摩尔）处理72小时的Calu-6细胞内ROS水平降低。然而，高剂量100微摩尔AMA处理的细胞中ROS水平升高。72小时时，AMA处理的细胞中O2.-水平显著升高。在AMA处理的细胞中，包括O2.-在内的ROS水平在10分钟内就开始升高。AMA处理降低了细胞内GSH含量。72小时时，AMA处理的Calu-6细胞中SOD活性上调。然而，AMA使过氧化氢酶活性下调。ROS清除剂替诺处理降低了细胞内ROS水平，这与凋亡的部分减少有关。外源性SOD和过氧化氢酶处理显著抑制了AMA处理的Calu-6细胞中线粒体跨膜电位（ΔΨm）的丧失。总之，我们的结果表明，细胞内ROS和GSH的变化影响了AMA处理的Calu-6细胞的凋亡。
