Mitochondrial and caspase pathways are involved in the induction of apoptosis by IB-MECA in ovarian cancer cell lines

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.