The roles of mitoferrin-2 in the process of arsenic trioxide-induced cell damage in human gliomas

Background Among glioma treatment strategies, arsenic trioxide (As 2 O 3 ) has shown efficacy as a therapeutic agent against human gliomas. However, the exact antitumor mechanism of action of As 2 O 3 is still unclear. Mitochondria are considered to be the major source of intracellular reactive oxygen species (ROS), which are known to be associated with As 2 O 3 -induced cell damage. Therefore, we investigated whether mitoferrin-2, a mitochondrial iron uptake transporter, participates in As 2 O 3 -induced cell killing in human gliomas. Methods Human glioma cell lines were used to explore the mechanism of As 2 O 3 ’s antitumor effects. First, expression of mitoferrin-2 was analyzed in glioma cells that were pretreated with As 2 O 3. Changes in ROS production and apoptosis were assessed. Furthermore, cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Results In the present study we found that As 2 O 3 induced ROS production and apoptosis in glioma cells. In addition, gene expression of mitoferrin-2, a mitochondrial iron uptake transporter, was increased 4 to 5 fold after exposure to As 2 O 3 (5 μM) for 48 hours. Furthermore, apoptosis and cytotoxicity induced by As 2 O 3 in glioma cells were decreased after silencing the mitoferrin-2 gene. Conclusions Our findings indicated that mitoferrin-2 participates in mitochondrial ROS-dependent mechanisms underlying As 2 O 3 -mediated damage in glioma cells.