Selenium is a widely studied dietary
anticancer agent. Among various
selenium compounds, the methylated forms appear to be particularly effective in
cancer prevention. Intracellular
glutathione (GSH) is known to be involved in the metabolism of many methylated forms of
selenium. In this study, we investigated the role of intracellular GSH in
methylseleninic acid (MSeA)-induced apoptosis in human
hepatoma (HepG(2)) cells. MSeA was shown to deplete intracellular GSH rapidly, preceding the typical apoptotic changes such as DNA fragmentation as measured by the TUNEL assay. When the intracellular GSH concentration was enhanced using N-acetylcysteiene (NAC) (a GSH synthesis precursor) and decreased using
buthionine sufoxamine (BSO) (a GSH synthesis inhibitor), NAC markedly augmented MSeA-induced apoptosis, while BSO significantly inhibited MSeA-induced apoptosis. Different from the effect of
sodium selenite, there was no measurable
superoxide radical level in MSeA-treated cells. These observations suggest that intracellular GSH mainly acts as a cofactor to facilitate MSeA-induced apoptosis, while its
antioxidant function becomes largely irrelevant. It is thus postulated that some
cancer cells, such as
liver cancer cells with higher level of intracellular GSH, would be more susceptible to MSeA cytotoxicity.