title: Activation of A2b adenosine receptor regulates ovarian cancer cell growth: involvement of Bax/Bcl-2 and caspase-3.
abstract: A2b adenosine receptor (A2bAR) acts as a potent regulator of cell growth in various cell lines. The present study was designed to understand the controlling mechanism of A2bAR agonist (NECA)-induced apoptosis in ovarian cancer cells. Real-time PCR and western blotting assays were used to evaluate the gene and protein expression profiles of A2bAR, respectively. MTT assay was used to study the cell proliferation effect of A2bAR agonist (NECA). Detection of apoptosis was conducted using annexin V-FITC/PI staining, caspase-3 activation assay, and the expression of Bax and Bcl-2 proteins analysis. The mitochondrial membrane potential (ΔΨM) was analyzed by employing JC-1 prob. The mRNA and protein expression levels of A2bAR in ovarian cancer cells were detected. NECA significantly reduced cell viability in a dose-dependent manner in OVCAR-3 and Caov-4 cell lines. The growth inhibition effect of NECA was related to the induction of cell apoptosis, which was manifested by annexin V-FITC staining, activation of caspase-3, and loss of mitochondrial membrane potentials (ΔΨm). In addition, downregulation of the regulatory protein Bcl-2 and upregulation of Bax protein by NECA were also observed. These findings demonstrated that NECA induces apoptosis via the mitochondrial signaling pathway. Thus, A2bAR agonists may be a potential agent for induction of apoptosis in ovarian cancer cells.
authors: a Department of Clinical Biochemistry, School of Pharmacy and Isfahan Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
authors: Sima
authors: S
authors: Hajiahmadi
authors: a Department of Clinical Biochemistry, School of Pharmacy and Isfahan Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
authors: Mojtaba
authors: M
authors: Panjehpour
authors: a Department of Clinical Biochemistry, School of Pharmacy and Isfahan Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
authors: Mahmoud
authors: M
authors: Aghaei
authors: b Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.
authors: Mahdi
authors: M
authors: Shabani
mesh_terms: D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology*; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D043704:Receptor, Adenosine A2B / Q000187:drug effects* / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: D058908:Adenosine A2 Receptor Agonists; C494826:BAX protein, human; D043704:Receptor, Adenosine A2B; D051028:bcl-2-Associated X Protein; D019830:Adenosine-5'-(N-ethylcarboxamide); D053148:Caspase 3
keywords: A2b adenosine receptor; RAA2b; apoptose; apoptosis; cancer ovarien; mitochondrial pathway; ovarian cancer; voie mitochondriale