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

Abstract

BackgroundAmong glioma treatment strategies, arsenic trioxide (As2O3) has shown efficacy as a therapeutic agent against human gliomas. However, the exact antitumor mechanism of action of As2O3 is still unclear. Mitochondria are considered to be the major source of intracellular reactive oxygen species (ROS), which are known to be associated with As2O3-induced cell damage. Therefore, we investigated whether mitoferrin-2, a mitochondrial iron uptake transporter, participates in As2O3-induced cell killing in human gliomas.MethodsHuman glioma cell lines were used to explore the mechanism of As2O3’s antitumor effects. First, expression of mitoferrin-2 was analyzed in glioma cells that were pretreated with As2O3. 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).ResultsIn the present study we found that As2O3 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 As2O3 (5 μM) for 48 hours. Furthermore, apoptosis and cytotoxicity induced by As2O3 in glioma cells were decreased after silencing the mitoferrin-2 gene.ConclusionsOur findings indicated that mitoferrin-2 participates in mitochondrial ROS-dependent mechanisms underlying As2O3-mediated damage in glioma cells.

Arsenic trioxide inhibits glioma cell growth through induction of telomerase displacement and telomere dysfunction

“…These results are similar to those of Wu [ 16 ], who studied the time-dependent effect of As 2 O 3 on U87 and U251 cell viability. Our study also indicates that after 48 h of treatment, the inhibitory effects significantly differ between 2 μM and 16 μM As 2 O 3 which is similar to the finding of Wang [ 17 ], who studied the dose-dependent effect of As 2 O 3 in U87 cells. We extended those findings by adding the study of SHG44 (another type of malignant human glioma) and C6 (mouse glioma cells) cell.…”

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

“…Cell viability, ROS levels, apoptosis and autophagy in human glioblastoma cell line have been shown to be regulated by As 2 O 3 [ 31 , 32 ] and/or As 2 O 3 in combination with other agents [ 33 ]. As 2 O 3 induces ROS production and apoptosis in glioma cells through the upregulation of the mitoferrin-2 gene [ 34 ]. Consistently with the results of those studies, we also found that intracellular ROS levels increased significantly after As 2 O 3 treatment.…”

Arsenic trioxide as a novel anti-glioma drug: a review

“…Silencing mitoferrin-2 led to a decrease in arsenic trioxide cytotoxicity. Therefore, the mitoferrin-2 transporter could participate in arsenic trioxide-induced cytotoxicity by promoting the production of ROS [ 45 ].…”