title: Auranofin induces mesothelioma cell death through oxidative stress and GSH depletion.
abstract: Mesothelioma is an aggressive tumor associated with asbestos exposure. Auranofin as an inhibitor of thioredoxin reductase (TrxR) affects many biological processes such as inflammation and proliferation. In the present study, we investigated the cellular effects of auranofin on patient-derived mesothelioma cells in relation to reactive oxygen species (ROS) and glutathione (GSH) levels. Basal TrxR1 levels have no difference between mesothelial cells and certain mesothelioma cells. In particular, ADA, CON and Hmeso mesothelioma cells showed lower levels of TrxR1 expression. Auranofin inhibited the proliferation of mesothelioma cells in a dose-dependent manner. Among mesothelioma cells were ADA and CON cells sensitive to auranofin. This agent also induced caspase-independent apoptosis and necrosis in ADA cells. In addition, auranofin increased ROS levels including O2(•-) and induced GSH depletion in mesothelioma cells. While N-acetyl cysteine (NAC) prevented cell death and decreased ROS levels in auranofin-treated mesothelioma cells, L-buthionine sulfoximine (BSO) intensified apoptosis and GSH depletion in these cells. In conclusion, auranofin induced mesothelioma cell death through oxidative stress and the death was regulated by the status of GSH content.
authors.affiliation: Department of Physiology, Medical School, Institute for Medical Sciences, Chonbuk National University, Jeonju 561‑180, Republic of Korea.
authors.forename: Bo Ra
authors.initials: BR
authors.lastname: You
authors.affiliation: Department of Physiology, Medical School, Institute for Medical Sciences, Chonbuk National University, Jeonju 561‑180, Republic of Korea.
authors.forename: Woo Hyun
authors.initials: WH
authors.lastname: Park
mesh_terms: D017209:Apoptosis; D001310:Auranofin / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D008654:Mesothelioma / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D054481:Thioredoxin Reductase 1 / Q000378:metabolism
chemical_list: D001310:Auranofin; C516124:TXNRD1 protein, human; D054481:Thioredoxin Reductase 1; D020169:Caspases; D005978:Glutathione