Auranofin induces mesothelioma cell death through oxidative stress and GSH depletion

You,Bo  Ra; Park,Woo  Hyun

doi:10.3892/or.2015.4382

Auranofin induces mesothelioma cell death through oxidative stress and GSH depletion

Authors:
- Bo Ra You
- Woo Hyun Park
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Affiliations: Department of Physiology, Medical School, Institute for Medical Sciences, Chonbuk National University, Jeonju 561‑180, Republic of Korea
Published online on: November 2, 2015 https://doi.org/10.3892/or.2015.4382
Pages: 546-551

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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.

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