Department of Physiology, Medical School, Research Institute for Endocrine Sciences, Chonbuk National University, Jeonju 561-180, Republic of Korea.
Oncol Rep. 2013 Jul;30(1):513-9. doi: 10.3892/or.2013.2447. Epub 2013 May 9.
Gallic acid (GA) is involved in various biological processes such as cell growth inhibition and apoptosis through changes in reactive oxygen species (ROS). In the present study, we investigated the effects of MAPK (MEK, JNK or p38) inhibitors on cell death in GA-induced A549 lung cancer cells in relation to ROS and glutathione (GSH). Treatment with 100 µM GA inhibited the growth of A549 cells and induced apoptosis and/or necrosis, which was accompanied by the loss of mitochondrial membrane potential (MMP; ∆Ψ(m)). GA increased ROS levels as well as GSH depletion in A549 cells at 24 h. MEK inhibitor seemed to enhance cell growth inhibition by GA. This inhibitor also increased cell death, MMP (∆Ψ(m)) loss and GSH depletion in GA-treated A549 cells. Both JNK and p38 inhibitors intensified growth inhibition, cell death, MMP (∆Ψ(m)) loss and GSH depletion by GA. However, none of the MAPK inhibitors significantly altered ROS levels in GA-treated A549 cells. In conclusion, MAPK inhibitors enhanced growth inhibition and death in GA-treated A549 cells, which were correlated with GSH depletion rather than ROS levels.
没食子酸（GA）通过改变活性氧（ROS）参与细胞生长抑制和细胞凋亡等各种生物过程。在本研究中，我们研究了 MAPK（MEK、JNK 或 p38）抑制剂对 GA 诱导的 A549 肺癌细胞死亡的影响，以及 ROS 和谷胱甘肽（GSH）之间的关系。用 100μM GA 处理可抑制 A549 细胞的生长，并诱导凋亡和/或坏死，同时伴随着线粒体膜电位（MMP；∆Ψ（m））的丧失。GA 在 24 小时内增加了 A549 细胞中的 ROS 水平和 GSH 耗竭。MEK 抑制剂似乎增强了 GA 引起的细胞生长抑制。该抑制剂还增加了 GA 处理的 A549 细胞中的细胞死亡、MMP（∆Ψ（m））丧失和 GSH 耗竭。JNK 和 p38 抑制剂均增强了 GA 引起的细胞生长抑制、细胞死亡、MMP（∆Ψ（m））丧失和 GSH 耗竭。然而，MAPK 抑制剂均未显著改变 GA 处理的 A549 细胞中的 ROS 水平。总之，MAPK 抑制剂增强了 GA 处理的 A549 细胞中的生长抑制和死亡，这与 GSH 耗竭而不是 ROS 水平有关。
