The JNK signaling pathway is involved in sodium-selenite-induced apoptosis mediated by reactive oxygen in HepG2 cells.

Selenium compounds as effective chemopreventive agents can induce apoptosis in tumor cells, and reactive oxygen species (ROS) are important mediators in apoptosis induced by various stimuli including chemopreventive agents. The major mitogen-activated protein kinases (MAPKs), c-JUN N-terminal kinase (JNK), p38 and extracelluar signal-regulated kinase (ERK) are three kinases that have been shown to regulate apoptosis. In this study, we showed that selenite-induced apoptosis in HepG2 cells was mediated by ROS that activated JNK to regulate apoptosis. The selenite-treated HepG2 cells showed a dose- and time-dependent decrease in cell viability that was coincident with increased the levels of the apoptosis rate. The levels of selenite-induced ROS as measured by 2', 7'-dichlorofluorescein diacetate (DCFH-DA) fluorescence also showed a dose- and time-dependent increase in HepG2 cells. The kinase activity of JNK was induced by selenite in a dose-dependent manner and HepG2 cells exposed to selenite (10 microM) for 4 h showed increased levels of phosphorylated JNK, which decreased when exposed for additional 4 h. In contrast, Sp600125, a specific inhibitor of JNK, remarkably blocked the apoptosis of HepG2 exposed to selenite. Furthermore, N-acetylcysteine (NAC), a known antioxidant, increased cell viability and decreased ROS generation. Moreover, NAC effectively blocked apoptosis and decreased the levels of phosphorylated JNK induced by selenite. These results revealed that JNK might be involved in selenite-induced ROS-mediated apoptosis in HepG2 cells.