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Synergistic Effects of Arsenic Trioxide and Radiation: Triggering the Intrinsic Pathway of Apoptosis Publisher Pubmed



Moloudi K1 ; Neshasteriz A2 ; Hosseini A3 ; Eyvazzadeh N4 ; Shomali M5 ; Eynali S6 ; Mirzaei E7 ; Azarnezhad A8, 9
Authors
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Authors Affiliations
  1. 1. Radiation Sciences Department, Faculty of allied Medicine school, Iran University of Medical Sciences, Tehran, Iran
  2. 2. Radiation biology research center, Iran University of medical sciences, Tehran, Iran
  3. 3. Department of Medical Biotechnology, Faculty of allied Medicine, Iran University of Medical Sciences, Tehran, Iran
  4. 4. Radiation Research Center, Faculty of Paramedicine, AJA University of Medical sciences, Tehran, Iran
  5. 5. Radiology Department, Faculty of allied Medicine, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Medical physics and Biomedical Engineering Department, school of Medicine, Tran University of Medical Sciences, Tehran, Iran
  7. 7. Microbiology Department, Faculty of Science, Islamic Azad University, Tehran, Iran
  8. 8. Cellular & Molecular Research Center, Kurdistan University of Medical Sciences, Sanandaj, Iran
  9. 9. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Source: Iranian Biomedical Journal Published:2017


Abstract

Background: Arsenic trioxide (ATO) has been reported as an effective anti-cancer and a US Food and Drug Administration (FDA) approved drug for treatment of some cancers. The aim of this study was to determine the underlying apoptosis molecular and cellular mechanisms of ATO in the presence or absence of ionizing radiation (IR) in vitro in the glioblastoma multiforme (GBM) cell line, U87MG. Methods: Cells were treated by different concentrations of ATO either in presence or absence of IR. Viability and apoptosis pathway of both treated and control groups were evaluated using MTT assay and the expression analysis of Bax, Bcl-2, and caspase-3 genes, respectively. All treatments were performed on 100-μm diameter spheroids. Results: Results showed a significant reduction in the survival of the cells in all treated groups. As expected, cell survival was much less in combination treatment than treatment with only ATO. Moreover, combination therapy made Bax and caspase-3 up-regulated and Bcl-2 down-regulated. Conclusion: ATO and radiation had a synergistic apoptotic effect on GBM cells by up-regulation of caspase-3 and alteration of the Bax-Bcl-2 balance; therefore, ATO may act as a potential anti-cancer agent against GBM cells through triggering the mitochondrial pathway of apoptosis. © 2017, Pasteur Institute of Iran. All rights reserved.
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