Auranofin induces apoptosis and necrosis in He La cells via oxidative stress and glutathione depletion

作者：You Bo Ra; Shin Hye Rim; Han Bo Ram; Kim Suhn Hee; Park Woo Hyun^*

来源：Molecular Medicine Reports, 2015, 11(2): 1428-1434.

DOI：10.3892/mmr.2014.2830

• auranofin
• apoptosis
• necrosis
• reactive oxygen species
• glutathione

Auranofin (Au), an inhibitor of thioredoxin reductase, is a known anti-cancer drug. In the present study, the anti-growth effect of Au on He La cervical cancer cells was examined in association with levels of reactive oxygen species (ROS) and glutathione (GSH). Au inhibited the growth of He La cells with an IC50 of similar to 2 mu M at 24 h. This agent induced apoptosis and necrosis, accompanied by the cleavage of poly (ADP-ribose) polymerase and loss of mitochondrial membrane potential. The pan-caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone, prevented apoptotic cell death and each of the assessed caspase inhibitors inhibited necrotic cell death induced by Au. With respect to the levels of ROS and GSH, Au increased intracellular O-2(center dot-) in the He La cells and induced GSH depletion. The pan-caspase inhibitor reduced the levels of O-2(center dot-) and GSH depletion in Au-treated He La cells. The antioxidant, N-acetyl cysteine, not only attenuated apoptosis and necrosis in the Au-treated He La cells, but also decreased the levels of O-2(center dot-) and GSH depletion in the cells. By contrast, L-buthionine sulfoximine, a GSH synthesis inhibitor, intensified cell death O-2(center dot-) and GSH depletion in the Au-treated HeLa cells. In conclusion, Au induced apoptosis and necrosis in HeLa cells via the induction of oxidative stress and the depletion of GSH.

• 出版日期2015-2