Possible role of glutathione in mitochondrial apoptosis of human oral squamous cell carcinoma caused by inorganic selenium compounds

Selenium (Se) is a very effective anti-cancer agent. We studied the effects of inorganic Se compounds on induction of apoptosis by which Se compounds exert cancer chemopreventive activity. With the use of HSC-3 human oral squamous cell carcinoma cells, the present study showed that treatment with Se for 72 h, in the form of SeO 2 and Na 2 SeO 3 , but not Na 2 SeO 4 , markedly induced apoptosis in a dose-dependent manner. Treatment of HSC-3 cells with 100 μM SeO 2 resulted in the caspase-3-like and -9-like activation. Se compounds induced a loss of mitochondrial membrane potential (AVm), but did not induce the generation of reactive oxygen species. Treatment with SeO 2 for 18 h resulted in 80% loss of reduced glutathione (GSH), which is known to be involved in the metabolism of Se. Treatment with N-acetyl-L-cysteine, or exogenous GSH, prevented the SeO 2 -induced apoptosis. Treatment with GSH led to the partial reverse in reduction of ΔΨm caused by SeO 2 , while buthionine sulfoximine augmented the SeO 2 - or Na 2 SeO 3 -induced apoptosis.These results suggest that modulation of the mitochondrial redox equilibrium by Se contributes to the mitochondrial pathway, regulating caspase-9-mediated apoptosis without a concurrent increase in ROS.