Department of Physiology, Medical School, Centers for Healthcare Technology Development Institutefor Medical Sciences, Chonbuk National University, JeonJu 561-180, Republic of Korea.
Int J Mol Med. 2010 Apr;25(4):657-62. doi: 10.3892/ijmm_00000389.
MG132 as a proteasome inhibitor has been shown to induce apoptotic cell death through formation of reactive oxygen species (ROS). Here, we investigated the effects of N-acetyl cysteine (NAC; a well-known antioxidant), L-buthionine sulfoximine (BSO; an inhibitor of GSH synthesis) or diethyldithiocarbamate (DDC; an inhibitor of Cu/Zn-SOD) on MG132-treated Calu-6 or A549 lung cancer cells in relation to cell growth, ROS and GSH levels. MG132 inhibited the growth of Calu-6 and A549 cells at 24 h. MG132 induced apoptosis in both cell lines, which was accompanied by the loss of mitochondrial membrane potential (MMP; DeltaPsim). ROS levels including O(2)(.-) were increased in both MG132-treated lung cells. MG132 also induced GSH depletion in both lung cell types. Treatment with 10 microM BSO or 1 microM DDC affected ROS and GSH levels in MG132-treated Calu-6 cells. However, these changes did not influence cell growth and death in the cells. NAC prevented cell growth inhibition and death in MG132-treated lung cells, which was accompanied by decreased ROS, but not by decreased GSH depletion. In conclusion, the changes of ROS and GSH by MG132, NAC, BSO or DDC were partially related to cell growth and death in the lung cancer cell lines Calu-6 and A549.
MG132 作为一种蛋白酶体抑制剂，已被证明通过形成活性氧物种 (ROS) 诱导细胞凋亡。在这里，我们研究了 N-乙酰半胱氨酸 (NAC; 一种众所周知的抗氧化剂)、L-丁硫氨酸亚砜 (BSO; 一种 GSH 合成抑制剂) 或二乙基二硫代氨基甲酸盐 (DDC; 一种 Cu/Zn-SOD 抑制剂) 在与细胞生长、ROS 和 GSH 水平相关的情况下对 MG132 处理的 Calu-6 或 A549 肺癌细胞的影响。MG132 在 24 小时内抑制 Calu-6 和 A549 细胞的生长。MG132 诱导两种细胞系凋亡，同时伴有线粒体膜电位 (MMP; DeltaPsim) 的丧失。两种 MG132 处理的肺细胞中 O(2)(.-) 的 ROS 水平增加。MG132 还诱导两种肺细胞类型的 GSH 耗竭。用 10 μM BSO 或 1 μM DDC 处理影响 MG132 处理的 Calu-6 细胞中的 ROS 和 GSH 水平。然而，这些变化并没有影响细胞在这些细胞中的生长和死亡。NAC 可防止 MG132 处理的肺细胞的生长抑制和死亡，同时伴有 ROS 的减少，但 GSH 耗竭没有减少。总之，MG132、NAC、BSO 或 DDC 引起的 ROS 和 GSH 的变化与 Calu-6 和 A549 肺癌细胞系的细胞生长和死亡部分相关。
