title: 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.affiliation: College of Pharmacy, Ewha Womans University, 11-1 Daehyun-dong, Seodaemun-ku, Seoul 120-750, Republic of Korea.
authors.forename: Sun-Jack
authors.initials: SJ
authors.lastname: Kim
authors.forename: Hye-Young
authors.initials: HY
authors.lastname: Min
authors.forename: Hwa-Jin
authors.initials: HJ
authors.lastname: Chung
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Park
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Hong
authors.forename: You-Jin
authors.initials: YJ
authors.lastname: Kang
authors.forename: Dae-Hong
authors.initials: DH
authors.lastname: Shin
authors.forename: Lak Shin
authors.initials: LS
authors.lastname: Jeong
authors.forename: Sang Kook
authors.initials: SK
authors.lastname: Lee
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D058909:Adenosine A3 Receptor Agonists; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000378:metabolism
chemical_list: D058909:Adenosine A3 Receptor Agonists; D000970:Antineoplastic Agents; C504222:thio-Cl-IB-MECA; D051057:Proto-Oncogene Proteins c-akt; D020169:Caspases; D000241:Adenosine