Department of Physiology, Medical School, Jeonbuk National University, 20 Geonji-ro, Deokjin, Jeonju 54907, Korea.
Molecules. 2022 Oct 28;27(21):7341. doi: 10.3390/molecules27217341.
Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) is a stable, cell-permeable redox-cycling nitroxide water-soluble superoxide dismutase (SOD) mimetic agent. However, little is known about its cytotoxic effects on lung-related cells. Thus, the present study investigated the effects of Tempol on cell growth and death as well as changes in reactive oxygen species (ROS) and glutathione (GSH) levels in Calu-6 and A549 lung cancer cells, normal lung WI-38 VA-13 cells, and primary pulmonary fibroblast cells. Results showed that Tempol (0.54 mM) dose-dependently inhibited the growth of lung cancer and normal cells with an IC of approximately 12 mM at 48 h. Tempol induced apoptosis in lung cells with loss of mitochondrial membrane potential (MMP; ∆Ψm) and activation of caspase-3. There was no significant difference in susceptibility to Tempol between lung cancer and normal cells. Z-VAD, a pan-caspase inhibitor, significantly decreased the number of annexin V-positive cells in Tempol-treated Calu-6, A549, and WI-38 VA-13 cells. A 2 mM concentration of Tempol increased ROS levels, including O in A549 and WI-38 VA-13 cells after 48 h, and specifically increased O levels in Calu-6 cells. In addition, Tempol increased the number of GSH-depleted cells in Calu-6, A549, and WI-38 VA-13 cells at 48 h. Z-VAD partially downregulated O levels and GSH depletion in Tempol-treated these cells. In conclusion, treatment with Tempol inhibited the growth of both lung cancer and normal cells via apoptosis and/or necrosis, which was correlated with increased O levels and GSH depletion.
替普瑞酮（4-羟基-2,2,6,6-四甲基哌啶-1-氧自由基）是一种稳定的、可穿透细胞膜的氧化还原循环氮氧自由基水溶性超氧化物歧化酶（SOD）模拟物。然而，关于其对肺部相关细胞的细胞毒性作用知之甚少。因此，本研究探讨了替普瑞酮对肺癌细胞（Calu-6 和 A549）、正常肺 WI-38VA-13 细胞和原代肺成纤维细胞的细胞生长和死亡以及活性氧（ROS）和谷胱甘肽（GSH）水平变化的影响。结果表明，替普瑞酮（0.54mM）呈剂量依赖性地抑制肺癌和正常细胞的生长，在 48 小时时 IC 约为 12mM。替普瑞酮诱导肺癌细胞的凋亡，表现为线粒体膜电位（MMP；∆Ψm）丧失和 caspase-3 激活。肺癌细胞和正常细胞对替普瑞酮的敏感性没有显著差异。泛半胱天冬酶抑制剂 Z-VAD 显著减少了替普瑞酮处理后的 Calu-6、A549 和 WI-38VA-13 细胞中 Annexin V 阳性细胞的数量。2mM 浓度的替普瑞酮在 48 小时后增加了 A549 和 WI-38VA-13 细胞中的 ROS 水平，包括 O，并且特异性地增加了 Calu-6 细胞中的 O 水平。此外，替普瑞酮在 48 小时时增加了 Calu-6、A549 和 WI-38VA-13 细胞中 GSH 耗竭细胞的数量。Z-VAD 部分下调了替普瑞酮处理这些细胞中的 O 水平和 GSH 耗竭。总之，替普瑞酮通过凋亡和/或坏死抑制肺癌和正常细胞的生长，这与 O 水平升高和 GSH 耗竭有关。
