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 (Δω _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 Δω _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.