title: The roles of mitoferrin-2 in the process of arsenic trioxide-induced cell damage in human gliomas.
abstract: 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.
authors.forename: Chunlei
authors.initials: C
authors.lastname: Wang
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Chen
authors.forename: Huichao
authors.initials: H
authors.lastname: Zou
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.forename: Yaohua
authors.initials: Y
authors.lastname: Liu
authors.forename: Shiguang
authors.initials: S
authors.lastname: Zhao
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D027682:Cation Transport Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D010087:Oxides / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D027682:Cation Transport Proteins; D010087:Oxides; D017382:Reactive Oxygen Species; C425684:SLC25A28 protein, human; D000077237:Arsenic Trioxide