Department of Physiology, Medical School, Institute for Medical Sciences, Chonbuk National University, JeonJu 561-180, Republic of Korea.
Toxicol In Vitro. 2010 Jun;24(4):1237-42. doi: 10.1016/j.tiv.2010.02.005. Epub 2010 Feb 8.
The inhibition of proteasome function has emerged as a useful strategy to maneuver apoptosis. In the present study, we evaluated the effects of MG132 as a proteasome inhibitor on the growth of Calu-6 lung cancer cells in relation to the cell cycle, cell death, reactive oxygen species (ROS) and glutathione (GSH) levels. MG132 dose-dependently inhibited the growth of Calu-6 cells at 24h. DNA flow cytometric analysis indicated that 1-30 microM MG132 induced an S phase arrest in Calu-6 cells. MG132 also induced apoptosis, which was accompanied by the loss of mitochondrial membrane potential (MMP; Deltapsi(m)). The pan-caspase inhibitor (Z-VAD) significantly rescued Calu-6 cells from MG132-induced cell death. The intracellular ROS levels including O(2)(-) were increased in MG132-treated Calu-6 cells. MG132 also increased GSH-depleted cell numbers in Calu-6 cells. Z-VAD significantly decreased O(2)(-) levels and GSH-depleted cell numbers in MG132-treated Calu-6 cells. In conclusion, MG132 inhibited the growth of Calu-6 cells via apoptosis and GSH depletion.
蛋白酶体功能的抑制已成为操纵细胞凋亡的一种有效策略。在本研究中，我们评估了 MG132 作为蛋白酶体抑制剂对 Calu-6 肺癌细胞生长的影响，涉及细胞周期、细胞死亡、活性氧 (ROS) 和谷胱甘肽 (GSH) 水平。MG132 浓度依赖性地在 24 小时内抑制 Calu-6 细胞的生长。DNA 流式细胞术分析表明，1-30 μM MG132 诱导 Calu-6 细胞的 S 期停滞。MG132 还诱导细胞凋亡，伴随着线粒体膜电位 (MMP; Deltapsi(m)) 的丧失。泛半胱天冬酶抑制剂 (Z-VAD) 显著挽救了 Calu-6 细胞免受 MG132 诱导的细胞死亡。MG132 处理的 Calu-6 细胞中包括 O(2)(-)在内的细胞内 ROS 水平增加。MG132 还增加了 Calu-6 细胞中 GSH 耗竭细胞的数量。Z-VAD 显著降低了 MG132 处理的 Calu-6 细胞中的 O(2)(-)水平和 GSH 耗竭细胞的数量。总之，MG132 通过细胞凋亡和 GSH 耗竭抑制 Calu-6 细胞的生长。
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