title: Mitochondrial and caspase pathways are involved in the induction of apoptosis by IB-MECA in ovarian cancer cell lines.
abstract: A3 adenosine receptor agonist (IB-MECA) has been shown to play important roles in cell proliferation and apoptosis in a variety of cancer cell lines. The present study was designed to understand the mechanism underlying IB-MECA-induced apoptosis in human ovarian cancer cell lines. The messenger RNA (mRNA) and protein expression levels of A3 adenosine receptor were detected in OVCAR-3 and Caov-4 ovarian cancer cells. IB-MECA was capable of decreasing intracellular cyclic adenosine monophosphate (cAMP) that was the reason for the presence of functional A3 adenosine receptor on the cell lines. IB-MECA significantly reduced cell viability in a dose-dependent manner. Cytotoxicity of IB-MECA was suppressed by MRS1220, an A3 adenosine receptor antagonist. The growth inhibition effect of IB-MECA was related to the induction of cell apoptosis, which was manifested by annexin V-FITC staining, activation of caspase-3 and caspase-9, and loss of mitochondrial membrane potentials (ΔΨm). In addition, downregulation of the regulatory protein Bcl-2 and upregulation of Bax protein by IB-MECA were also observed. These findings demonstrated that IB-MECA induces apoptosis via the mitochondrial signaling pathway. These suggest that A3 adenosine receptor agonists may be a potential agent for induction of apoptosis in human ovarian cancer cells.
authors.affiliation: Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, P.O. Box: 81746-73461, Isfahan, Iran.
authors.forename: Hamideh
authors.initials: H
authors.lastname: Abedi
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Aghaei
authors.forename: Mojtaba
authors.initials: M
authors.lastname: Panjehpour
authors.forename: Sima
authors.initials: S
authors.lastname: Hajiahmadi
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D058909:Adenosine A3 Receptor Agonists / Q000494:pharmacology; D058918:Adenosine A3 Receptor Antagonists / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D043684:Receptor, Adenosine A3 / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: D058909:Adenosine A3 Receptor Agonists; D058918:Adenosine A3 Receptor Antagonists; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D043684:Receptor, Adenosine A3; C084956:N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine; D000242:Cyclic AMP; D020169:Caspases; D000241:Adenosine
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