title: A3 Adenosine Receptor Agonist Inhibited Survival of Breast Cancer Stem Cells via GLI-1 and ERK1/2 Pathway.
abstract: Numerous studies have demonstrated the role of A3 adenosine receptor (A3AR) and signaling pathways in the multiple aspects of the tumor. However, there is a little study about the function of A3AR in the biological processes of cancer stem cells (CSCs). CSCs have a critical role in the maintenance and survival of breast cancer. The aim of current study was to investigate the effect of A3AR agonist on breast cancer stem cells (BCSCs). XTT assay showed antiproliferative effect of A3AR agonist (Cl-IB-MECA) on BCSCs. Our results also demonstrated that A3AR agonist reduces mammosphere formation in a dose-dependent manner. Flow cytometry analysis showed that A3AR agonist induces G1 cell cycle arrest and apoptosis in BCSCs. Western blot assay showed that A3AR agonist inhibits the expression of cell cycle and apoptotic regulatory proteins as well as the expression of ERK1/2 and GLI-1 proteins. Finally, these findings propose that A3AR agonist induces cell cycle arrest and apoptosis in BCSCs by inhibition of ERK1/2 and GLI-1 cascade. J. Cell. Biochem. 118: 2909-2920, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Seyyed Mehdi
authors.initials: SM
authors.lastname: Jafari
authors.affiliation: Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.|Bioinformatics Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Mojtaba
authors.initials: M
authors.lastname: Panjehpour
authors.affiliation: Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.|Isfahan Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Mahmoud
authors.identifier: 0000-0002-1775-8761
authors.initials: M
authors.lastname: Aghaei
authors.affiliation: Medical Laboratory Research Center, Golestan University of Medical Sciences, Gorgan, Iran.
authors.forename: Hamid Reza
authors.initials: HR
authors.lastname: Joshaghani
authors.affiliation: Faculty of Medicine, Department of Medical Biotechnology and Nanotechnology, Zanjan University of Medical Sciences, Zanjan, Iran.
authors.forename: Seyed Ehsan
authors.initials: SE
authors.lastname: Enderami
mesh_terms: D058909:Adenosine A3 Receptor Agonists / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D061986:MCF-7 Cells; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D043684:Receptor, Adenosine A3 / Q000235:genetics / Q000378:metabolism*; D000071676:Zinc Finger Protein GLI1 / Q000378:metabolism*
chemical_list: D058909:Adenosine A3 Receptor Agonists; C400551:GLI1 protein, human; D009363:Neoplasm Proteins; D043684:Receptor, Adenosine A3; D000071676:Zinc Finger Protein GLI1; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: A3 ADENOSINE RECEPTOR; BREAST CANCER STEM CELLS; ERK1/2; GLI-1