A novel adenosine analong, Thio-Cl-IB-MECA induces G_(0)/G_(1) cell cycle arrest and apoptosis in human promyelocytic leukemia HL-60 cells

다국어 초록 (Multilingual Abstract)

Human A_(3) adenosine receptor(A_(3)AR) agonists have been shown to play important roles in several physiological and pathological processes, including growth inhibition of human cancer cells. On the line, we recently found that n novel adenosine analog 2-chloro-N^(6)-(3-iodobenzyl)-4`-thioadenosine-5`-N-methyluronamide (thio-Cl-IB-MECA) was a potent human A_(3)AR agonist and is superior to a known agonist Cl-IB-MECA[JeonLS,Jin DZ,Kim HO,Shin DH,Moon HR,Gunaga P,et al. J Med Chem 2003;46;3775]Here wwe report thar novel A_(3)AR agonist thio-Cl-IB-MECA inhibied the growth of human promyelocytic leukemia HL-60 cells by arresting cell cycle and induction apoptosis Thio-Cl-IB-MECA induced the cell cycle arrest of G_(0)/G_(1) in the early time and at lower conentration (up to 25㎛) At higher concentration (50㎛)the apoptotic cell deaths were manifested by obsercation of the increase of sub-G_(0)to S phase Further study revealed that the growth inhibitort activity of thio-Cl-IB-MECA is also related with the modulation of Wnt signaling pathway The levels of β-catenin, phosphorylated forms of GSK-β and were Akt were down-regulated by the tretment of thio-Cl-IB-MECA(10nM) in a time-dependent manner providing one of plausible mechanistic evidence for the involvement of the Wnt signaling pathway in the HL-60 cell growth inhibitory effects by thio-Cl_IB-MECA These results suggest that a novel A_(3)AR agonist thio-CL-IB-MECA can compound in the potential therapeutic value of the tretment of lekemia