Relationship between intracellular glutathione level and the mode of cell death induced by pingyangmycin

The effects of intracellular glutathione (GSH) concentration on the toxicity of pingyangmycin in human squamous cell carcinoma cell line were evaluated. By using the GSH synthesis inhibitor D,L-buthionine-S,R-sulfoximine and the precursor of cysteine 2-oxothiazolidine-4-carboxylate (OTZ), intracellular glutathione levels were artificially changed. After exposed to different GSH concentrations cultured tumor cells were treated with pingyangmycin and the resultant mode of cell death was analyzed using morphological and biochemical criteria. It was found that the toxicity of pingyangmycin was obviously increased to cultured tumor cells on lowering GSH levels, with the mode of cell death switching from necrosis to apoptosis. In contract, treatment with OTZ increased GSH level compared with that of control cells, inhibited cell death induced by pingyangmycin via a necrotic rather than apoptotic process. These observations suggest that modulation of GSH levels effects the toxicity of pingyangmycin and that GSH influences the mode of cell death induced by pingyangmycin.