Auranofin induces mesothelioma cell death through oxidative stress and GSH depletion
| Autor: | Woo Hyun Park, Bo Ra You |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Mesothelioma
0301 basic medicine Thioredoxin Reductase 1 Cancer Research Programmed cell death Auranofin Necrosis Cell Survival Apoptosis Biology medicine.disease_cause 03 medical and health sciences chemistry.chemical_compound Cell Line Tumor medicine Humans neoplasms chemistry.chemical_classification Reactive oxygen species General Medicine Glutathione respiratory system medicine.disease respiratory tract diseases Gene Expression Regulation Neoplastic Oxidative Stress 030104 developmental biology Oncology chemistry Caspases Cancer research medicine.symptom Oxidative stress medicine.drug |
| Zdroj: | Oncology Reports. 35:546-551 |
| ISSN: | 1791-2431 1021-335X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|