Arsenic trioxide (As 2 O 3) has been shown to induce apoptosis in hepatocellular carcinoma cells. However, the molecular mechanism of As 2 O 3-induced apoptosis in the hepatocellular carcinoma cells remains poorly understood. Here, we investigated the impact of As 2 O 3 exposure on the human hepatocellular carcinoma cell line HepG2 and examined the underlying mechanism of cell death. As 2 O 3 induced apoptosis of HepG2 cells in a dose-and time-dependent manner and caused a massive production of

more »

... reactive oxygen species (ROS). The antioxidant N-acetylcysteine (NAC) was able to prevent As 2 O 3-induced cell death, implying an involvement of ROS in the induction of As 2 O 3-triggered apoptosis. Furthermore, As 2 O 3 initiated apoptosis by triggering of the mitochondria apoptotic pathway as indicated by inhibited Bcl-2 expression, a collapse of the mitochondrial membrane potential (MMP), release of cytochrome c and activation of the caspase cascade. However, these As 2 O 3-induced events can be prevented by NAC. Taken together, these findings suggest that the As 2 O 3 induced apoptosis through a ROS-mediated mitochondrial pathway and activation of caspases.