You Bo Ra, Park Woo Hyun
Department of Physiology, Medical School, Institute for Medical Sciences, Chonbuk National University, Jeonju 561‑180, Republic of Korea.
Oncol Rep. 2016 Jan;35(1):546-51. doi: 10.3892/or.2015.4382. Epub 2015 Nov 2.
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.
间皮瘤是一种与接触石棉相关的侵袭性肿瘤。金诺芬作为硫氧还蛋白还原酶（TrxR）的抑制剂，会影响许多生物学过程，如炎症和增殖。在本研究中，我们研究了金诺芬对源自患者的间皮瘤细胞的细胞效应，以及与活性氧（ROS）和谷胱甘肽（GSH）水平的关系。间皮细胞和某些间皮瘤细胞之间的基础TrxR1水平没有差异。特别是，ADA、CON和Hmeso间皮瘤细胞显示出较低水平的TrxR1表达。金诺芬以剂量依赖性方式抑制间皮瘤细胞的增殖。在间皮瘤细胞中，ADA和CON细胞对金诺芬敏感。该药物还在ADA细胞中诱导了非半胱天冬酶依赖性凋亡和坏死。此外，金诺芬增加了包括O2(•-)在内的ROS水平，并诱导间皮瘤细胞中的GSH耗竭。虽然N-乙酰半胱氨酸（NAC）可防止金诺芬处理的间皮瘤细胞死亡并降低ROS水平，但L-丁硫氨酸亚砜胺（BSO）会加剧这些细胞中的凋亡和GSH耗竭。总之，金诺芬通过氧化应激诱导间皮瘤细胞死亡，且细胞死亡受GSH含量状态的调节。
