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.

Abstract

Human A3 adenosine receptor (A3AR) 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-N6-(3-iodobenzyl)-4'-thioadenosine-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 microM) and apoptotic cell death at a higher concentration (80 microM), which were manifested by down-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-Cl-IB-MECA. These data might suggest the potential therapeutic value of an adenosine analog in the treatment of human lung cancer.

• Authors: Sun-Jack Kim, Hye-Young Min, Hwa-Jin Chung, Eun-Jung Park, Ji-Young Hong, You-Jin Kang, Dae-Hong Shin, Lak Shin Jeong, Sang Kook Lee
• Journal: Cancer letters (Cancer Lett) Vol. 264 Issue 2 Pg. 309-15 (Jun 18 2008) ISSN: 0304-3835 [Print] Ireland
• PMID: 18321638 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adenosine A3 Receptor Agonists
• Antineoplastic Agents
• thio-Cl-IB-MECA
• Proto-Oncogene Proteins c-akt
• Caspases
• Adenosine

Topics

• Adenosine (analogs & derivatives, pharmacology)
• Adenosine A3 Receptor Agonists
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Blotting, Western
• Caspases (drug effects, metabolism)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Enzyme Activation (drug effects)
• Gene Expression (drug effects)
• Humans
• Lung Neoplasms (drug therapy)
• Proto-Oncogene Proteins c-akt (drug effects, metabolism)