Department of Physiology, Medical School, Institute for Medical Sciences, Chonbuk National University, JeonJu, Republic of Korea.
Drug Chem Toxicol. 2011 Jan;34(1):38-44. doi: 10.3109/01480545.2010.494182. Epub 2010 Oct 18.
Gallic acid (GA), as a polyhydroxylphenolic compound, has various biological properties, including an anticancer effect. However, little is known about the toxicological effect of GA in primary normal cells. In the present study, we investigated the molecular mechanisms of GA on human pulmonary fibroblast (HPF) cell death in relation to apoptosis. HPF cell growth was dose dependently diminished with an IC(50) of approximately 400 μM of GA at 24 hours. GA-induced HPF cell death was accompanied by the loss of mitochondrial membrane potential (MMP; ΔΨ(m)). All the tested caspase inhibitors (e.g., pan-caspase, caspase-3, -8, or -9 inhibitor) did not rescue HPF cells from GA-induced cell death. GA increased reactive oxygen species (ROS) levels and glutathione (GSH)-depleted cell numbers. Caspase inhibitors partially altered ROS levels, but did not reduce GSH-depleted cell number, in GA-treated HPF cells. In conclusion, we demonstrated that GA induced the growth inhibition and death of HPF cells, which was accompanied by ROS increase and GSH depletion.
没食子酸（GA）作为一种多羟基酚类化合物，具有多种生物学特性，包括抗癌作用。然而，关于 GA 在原代正常细胞中的毒理学效应知之甚少。在本研究中，我们研究了 GA 对人肺成纤维细胞（HPF）细胞凋亡相关死亡的分子机制。GA 呈剂量依赖性地抑制 HPF 细胞生长，在 24 小时时 IC50 约为 400 μM 的 GA。GA 诱导的 HPF 细胞死亡伴随着线粒体膜电位（MMP；ΔΨ（m））的丧失。所有测试的半胱天冬酶抑制剂（例如，泛半胱天冬酶、半胱天冬酶-3、-8 或-9 抑制剂）均不能挽救 GA 诱导的 HPF 细胞死亡。GA 增加活性氧（ROS）水平和谷胱甘肽（GSH）耗竭细胞数量。半胱天冬酶抑制剂部分改变了 GA 处理的 HPF 细胞中的 ROS 水平，但并未减少 GSH 耗竭细胞数量。总之，我们证明了 GA 诱导 HPF 细胞的生长抑制和死亡，这伴随着 ROS 增加和 GSH 耗竭。
