Department of Physiology, Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju 561-180, Korea.
Mol Med Rep. 2011 Jan-Feb;4(1):193-04. doi: 10.3892/mmr.2010.361. Epub 2010 Sep 10.
Gallic acid (GA) has various biological properties, including an anti-cancer effect. However, little is known about the toxicological effect of GA in primary normal cells in relation to mitogen-activated protein kinase (MAPK) signaling. In this study, we investigated the effects of MAPK (MEK, JNK or p38) inhibitors on GA-treated human pulmonary fibroblast (HPF) cells in relation to cell growth inhibition, cell death, reactive oxygen species (ROS) and glutathione (GSH). GA induced HPF cell growth inhibition and cell death at 24 h, which was accompanied by the loss of mitochondrial membrane potential (MMP; ∆ψm). GA increased ROS levels and GSH-depleted cell numbers in the HPF cells. The MEK inhibitor did not affect cell growth inhibition, cell death, ROS and GSH levels in the GA-treated HPF cells. The JNK inhibitor slightly enhanced cell growth inhibition by GA, while the p38 inhibitor significantly prevented the growth inhibition. Both JNK and p38 inhibitors did not affect cell death, ROS and GSH levels in the GA-treated HPF cells. In conclusion, MAPK inhibitors differentially affected the growth inhibition of GA-treated HPF cells, which were not related to cell death, ROS and GSH levels.
没食子酸（GA）具有多种生物学特性，包括抗癌作用。然而，关于 GA 在与丝裂原活化蛋白激酶（MAPK）信号相关的原代正常细胞中的毒理学效应知之甚少。在这项研究中，我们研究了 MAPK（MEK、JNK 或 p38）抑制剂对 GA 处理的人肺成纤维细胞（HPF）细胞的影响，涉及细胞生长抑制、细胞死亡、活性氧（ROS）和谷胱甘肽（GSH）。GA 在 24 小时诱导 HPF 细胞生长抑制和细胞死亡，同时伴随着线粒体膜电位（MMP；∆ψm）的丧失。GA 增加了 ROS 水平和 GA 处理的 HPF 细胞中 GSH 耗竭细胞的数量。MEK 抑制剂对 GA 处理的 HPF 细胞中细胞生长抑制、细胞死亡、ROS 和 GSH 水平没有影响。JNK 抑制剂轻度增强了 GA 引起的细胞生长抑制，而 p38 抑制剂则显著阻止了生长抑制。JNK 和 p38 抑制剂均不影响 GA 处理的 HPF 细胞中的细胞死亡、ROS 和 GSH 水平。总之，MAPK 抑制剂对 GA 处理的 HPF 细胞的生长抑制有差异影响，与细胞死亡、ROS 和 GSH 水平无关。
