Auranofin induces mesothelioma cell death through oxidative stress and GSH depletion

Area of Science:

• Oncology
• Biochemistry
• Cell Biology

Background:

• Mesothelioma is an aggressive cancer linked to asbestos exposure.
• Auranofin inhibits thioredoxin reductase (TrxR), impacting inflammation and proliferation.
• TrxR1 expression varies in mesothelioma cells, with some showing lower levels.

Purpose of the Study:

• To investigate auranofin's cellular effects on patient-derived mesothelioma cells.
• To examine the roles of reactive oxygen species (ROS) and glutathione (GSH) in auranofin's action.
• To determine if NAC or BSO could modulate auranofin's effects.

Main Methods:

• Culturing patient-derived mesothelioma cells (ADA, CON, Hmeso).
• Treating cells with auranofin and measuring proliferation, apoptosis, necrosis, ROS, and GSH levels.
• Using N-acetyl cysteine (NAC) and L-buthionine sulfoximine (BSO) to assess the role of oxidative stress and GSH.

Main Results:

• Auranofin inhibited mesothelioma cell proliferation dose-dependently.
• ADA and CON cells were sensitive to auranofin, which induced caspase-independent apoptosis and necrosis.
• Auranofin increased ROS and depleted GSH in mesothelioma cells.
• NAC mitigated auranofin's effects, while BSO exacerbated them.

Conclusions:

• Auranofin induces mesothelioma cell death via oxidative stress.
• Glutathione (GSH) levels regulate the cell death induced by auranofin.
• Targeting TrxR with auranofin presents a potential therapeutic strategy for mesothelioma.