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

Cellular & molecular biology letters(2018)

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摘要
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.
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关键词
Arsenic trioxide (As2O3),Reactive oxygen species (ROS),Glioma,Apoptosis
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