Arsenic trioxide induces apoptosis and the formation of reactive oxygen species in rat glioma cells

BACKGROUND: Arsenic trioxide (As(2)O(3)) has a dramatic therapeutic effect on acute promyelocytic leukemia (APL) patients. It can also cause apoptosis in various tumor cells. This study investigated whether As(2)O(3) has an antitumor effect on glioma and explored the underlying mechanism. RESULTS: MTT and trypan blue assays showed that As(2)O(3) remarkably inhibited growth of C6 and 9 L glioma cells. Cell viability decreased in glioma cells to a greater extent than in normal glia cells. The annexin V-FITC/PI and Hoechest/PI staining assays revealed a significant increase in apoptosis that correlated with the duration of As(2)O(3) treatment and occurred in glioma cells to a greater extent than in normal glial cells. As(2)O(3) treatment induced reactive oxygen species (ROS) production in C6 and 9 L cells in a time-dependent manner. Cells pretreated with the antioxidant N-acetylcysteine (NAC) showed significantly lower As(2)O(3)-induced ROS generation. As(2)O(3) significantly inhibited the expression of the anti-apoptotic gene Bcl-2, and upregulated the proapoptotic gene Bax in both C6 and 9 L glioma cells in a time-dependent manner. CONCLUSIONS: As(2)O(3) can significantly inhibit the growth of glioma cells and it can induce cell apoptosis in a time- and concentration-dependent manner. ROS were found to be responsible for apoptosis in glioma cells induced by As(2)O(3). These results suggest As(2)O(3) is a promising agent for the treatment of glioma.