Inhibition of cell proliferation through cell cycle arrest and apoptosis by thio-Cl-IB-MECA, a novel A3 adenosine receptor agonist, in human lung cancer cells

Human A(3) adenosine receptor (A(3)AR) agonists showed the anti-tumor activity in various in vitro and in vivo studies. The present study investigates the anti-proliferative effect of a novel adenosine analog 2-chloro-N-6-(3-iodobenzyl)-4'-thioideiiosine-5'-N-methyluronamide (thio-Cl-IB-MECA) in A549 human lung cancer cells. Thio-Cl-IB-MECA induced arrest of cell cycle progression in G0/G1 phase at lower concentrations (up to 20 mu M) and apoptotic cell death at a higher concentration (80 mu M), which were manifested by clown-regulation of cyclin D1, c-myc, and CDK4, activation of caspase-3 and -9, and cleavage of poly(ADP-ribose) polymerase (PARP). The activation of Akt-mediated signaling was also inhibited by treatment with thio-G-IB-MECA. These data might suggest the potential therapeutic value of an adenosine analog in the treatment of human lung cancer. (C) 2008 Elsevier Ireland Ltd. All rights reserved.