title: MAPK inhibitors augment gallic acid-induced A549 lung cancer cell death through the enhancement of glutathione depletion.
abstract: 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.
authors: Department of Physiology, Medical School, Research Institute for Endocrine Sciences, Chonbuk National University, Jeonju 561-180, Republic of Korea. parkwh71@chonbuk.ac.kr
authors: Woo Hyun
authors: WH
authors: Park
authors: Suhn Hee
authors: SH
authors: Kim
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005707:Gallic Acid / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017382:Reactive Oxygen Species; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: D047428:Protein Kinase Inhibitors; D017382:Reactive Oxygen Species; D005707:Gallic Acid; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D005978:Glutathione