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The roles of mitoferrin-2 in the process of arsenic trioxide-induced cell damage in human gliomas
WANG Ligang *
The first affiliated hospital of Harbin Medical University
*Correspondence author
#Submitted by
Subject:
Funding: Doctoral Scientific Fund Project of the Minitry of Education of China(No.20132307120028)
Opened online:17 May 2017
Accepted by: none
Citation: WANG Ligang.The roles of mitoferrin-2 in the process of arsenic trioxide-induced cell damage in human gliomas[OL]. [17 May 2017] http://en.paper.edu.cn/en_releasepaper/content/4733708
 
 
Background: Among 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. Methods: Human 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). Results: In 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. Conclusions: Our findings indicated that mitoferrin-2 participates in mitochondrial ROS-dependent mechanisms underlying As2O3-mediated damage in glioma cells.
Keywords: Glioma, Mitoferrin-2, Apoptosis, Oxidative stress, Arsenic trioxidekey
 
 
 

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