Reactive oxygen species from mitochondria mediate SW480 cells apoptosis induced by Na2SeO3

A number of selenium compounds have been found to inhibit tumorigenesis in a variety of animal and cell models. In order to explore the molecular mechanism involved in the anticarcinogenesis activity of selenium, we examined the effects of sodium selenite on cell viabilty, generation of reactive oxygen species (ROS), and mitochondrial transmembrane potential (DeltaPsi(m)) in human colonic carcinoma cells SW480. The result from MTT test showed that sodium selenite reduced cell viability. Morophologic and flow cytometric results indicated that Na2SeO3 induced the apoptosis of SW480 cells. Na2SeO3 increased the generation of intracellular ROS, whereas BAPTA-AM, rotenone, and NaCN completely inhibited the increase of ROS induced by Na2SeO3. Na2SeO3 also caused the disruption of DeltaPsi(m). The intracellular ROS increase and apoptosis induced by Na2SeO3 were significantly decreased by superoxide dismutase (SOD), catalase. These data suggest that the ROS mediate apoptosis induced by Na2SeO3 and mitochondria may be a major source of Na2SeO3-induced ROS.