Dual role of glutathione in selenite-induced oxidative stress and apoptosis in human hepatoma cells

It is well known that glutathione, the major intracellular antioxidant, is closely involved in the metabolism and bioactivity of selenium. In the pres ent study, glutathione was demonstrated to play a dual role on selenite (Se )-induced oxidative stress and apoptosis in human hepatoma HepG(2) cells. T he experiment was carried out in two different modes to modulate intracellu lar reduced glutathione (GSH) content. In Mode A (pretreatment), cells were pretreated with N-acetylcysteine (NAC), buthionine sulfoximine (BSO), or G SH prior to Se exposure. In Mode B (simultaneous treatment), cells were tre ated with Se and NAC, BSO, or GSH simultaneously. It was found that Se-indu ced oxidative stress and apoptosis are closely related to the intracellular level of GSH. Both the increase and depletion of GSH content significantly enhanced Se-induced oxidative stress and apoptosis in HepG(2) cells. Resul ts from this study clearly demonstrated that GSH has a dual role in the eff ects of Se on cancer cells: (i) GSH acts as a pro-oxidant, facilitating Se- induced oxidative stress, and (ii) GSH acts as an antioxidant, protecting a gainst Se-induced oxidative stress and apoptosis. Understanding such a uniq ue association between GSH and Se may help to explain the controversy in th e literature over the complex relationship between selenium and glutathione , and ultimately the capability of selenium to prevent cancer. (C) 2000 Els evier Science Inc.