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

Auranofin (Au), an inhibitor of thioredoxin reductase, is a known anticancer drug. In the present study, the antigrowth effect of Au on HeLa cervical cancer cells was examined in association with levels of reactive oxygen species (ROS) and glutathione (GSH). Au inhibited the growth of HeLa cells with an IC50 of ∼2 μM at 24 h. This agent induced apoptosis and necrosis, accompanied by the cleavage of poly (ADPribose) polymerase and loss of mitochondrial membrane potential. The pancaspase inhibitor, benzyloxycarbonylValAlaAspfluoromethylketone, 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 O2-in the HeLa cells and induced GSH depletion. The pancaspase inhibitor reduced the levels of O2-and GSH depletion in Autreated HeLa cells. The antioxidant, Nacetyl cysteine, not only attenuated apoptosis and necrosis in the Autreated HeLa cells, but also decreased the levels of O2-and GSH depletion in the cells. By contrast, Lbuthionine sulfoximine, a GSH synthesis inhibitor, intensified cell death O2-and GSH depletion in the Autreated HeLa cells. In conclusion, Au induced apoptosis and necrosis in HeLa cells via the induction of oxidative stress and the depletion of GSH.