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Investigation the Effect of Adenosine A1 Receptor Agonist and Antagonist on P53 Gene Expression, and Apoptosis Pathways and Rate in U87mg Multiform Glioblastoma Publisher



Zamanirarani F1 ; Shrifiandastjerdi Z2 ; Valiani A2 ; Zamanirarani M2 ; Kargarabargouei E2 ; Eftekhar E3 ; Pourentezari M4 ; Mohajeransari J2
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Authors Affiliations
  1. 1. Department of Anatomical Sciences, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  2. 2. Department of Anatomical Sciences, School of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
  3. 3. Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Science, Bandar Abbas, Iran
  4. 4. Department of Biology and Anatomical Sciences, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

Source: Journal of Isfahan Medical School Published:2021


Abstract

Background: Improper prognosis in brain cancers requires new treatments. Using family of purinergic receptors with confirmed apoptotic effect can be beneficial. As the role of type A1 receptor in multiform glioblastoma in relation to the P53 gene and apoptotic pathways is nor reported, we studied the role of agonist (N6-cyclopentyladenosine or CPA) and antagonist (8-cyclopentyl-1,3-dipropylxanthine or DPCPX) of this receptor on cell apoptosis and also expression of P53 genes and caspases 7, 8, and 9. Methods: In this study, MTT assay was used to investigate the rate of cellular proliferation, and flowcytometry method with annexin and Pi was also used to investigate early and late cell apoptosis. To evaluate the internal and external apoptotic pathways expression of P53 genes and caspases 7, 8, and 9, real-time reverse transcription polymerase chain reaction (real-time RT PCR) was used. Findings: The treatment of U87Mg cells with DPCPX increased the expression of P53 gene. Expression of caspase 7 as an executive caspase and caspase 9 as a caspase of the mitochondrial pathway of apoptosis increased, but no expression change was observed in the caspase 8 gene. Conclusion: The results of MTT and flowcytometry showed that DPCPX, in addition to suppressing cell proliferation, stimulated apoptosis in U87Mg cells. Inhibition of adenosine A1 receptors by stimulating the expression of genes involved in apoptotic pathways, especially mitochondrial pathway genes, suppressed cell proliferation and induced apoptosis in U87Mg cells. © 2021 Isfahan University of Medical Sciences(IUMS). All rights reserved.
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