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

Selenium (Sc) is a very effective anti-cancer agent. We studied the effects of inorganic Sc 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 Sc for 72 h, in the form of SeO₂ and Na₂SeO₃, but not Na ₂SeO₄, markedly induced apoptosis in a dose-dependent manner. Treatment of HSC-3 cells with 100 μM SeO₂ resulted in the caspasc-3-like and -9-like activation. Se compounds induced a loss of mitochondrial membrane potential (ΔΨm), but did not induce the generation of reactive oxygen species. Treatment with SeO₂ for 18 h resulted in 80% loss of reduced glutathione (GSH), which is known to be involved in the metabolism of Sc. Treatment with N-acctyl-L-cysteinc, or exogenous GSH, prevented the SeO₂-induced apoptosis. Treatment with GSH led to the partial reverse in reduction of ΔΨm caused by SeO₂ while buthionine sulfoximine augmented the SeO_2- or Na₂SeO _3- induced apoptosis. These results suggest that modulation of the mitochondrial redox equilibrium by Se contributes to the mitochondrial pathway, regulating caspasc-9-mediated apoptosis without a concurrent increase in ROS.