title: Thio-Cl-IB-MECA, a novel A₃ adenosine receptor agonist, suppresses angiogenesis by regulating PI3K/AKT/mTOR and ERK signaling in endothelial cells.
abstract: Although A₃AR agonists exhibit a variety of biological activities including anticancer effects, their possible anti-angiogenic effects have not yet been investigated. In the present study, we assayed the anti-angiogenic activity of thio-Cl-IB-MECA, a novel A₃AR agonist, in cultured HUVECs and mES/EB-derived endothelial cells. Thio-Cl-IB-MECA inhibited migration and tube formation by endothelial cells and dramatically decreased ex vivo microvessel sprouting in cultured mouse aortic rings. The anti-angiogenic activity of thio-Cl-IB-MECA was associated with suppression of the expression of the endothelial biomarker PECAM via regulation of PI3K/AKT/mTOR and ERK signaling in mES/EB-derived endothelial cells.
authors.affiliation: College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Gi Dae
authors.initials: GD
authors.lastname: Kim
authors.forename: Jedo
authors.initials: J
authors.lastname: Oh
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* / Q000737:chemistry / Q000494:pharmacology; D058909:Adenosine A3 Receptor Agonists / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D058732:Embryoid Bodies / Q000166:cytology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D000241:Adenosine; D058909:Adenosine A3 Receptor Agonists; D015415:Biomarkers; D048049:Extracellular Signal-Regulated MAP Kinases; D019869:Phosphatidylinositol 3-Kinases; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C504222:thio-Cl-IB-MECA; C546842:MTOR protein, human
keywords: 2-chloro-N(6)-(3-iodobenzyl)-4′-thioadenosine-5′-N-methyluronamide; 2-chloro-N(6)-(3-iodobenzyl)-adenosine-5′-N-methylcarboxamide; A(3) adenosine receptor; A(3)AR; Anti-angiogenesis; Cl-IB-MECA; EB; ERK; Endothelial cells; HUVECs; IB-MECA; N(6)-(3-iodobenzyl)adenosine-5′-N-methyluronamide; PECAM; PI3K; PI3K/AKT/mTOR; Thio-Cl-IB-MECA; embryoid body; extracellular signal-regulated kinase; human umbilical vein endothelial cells; mES; mouse embryonic stem; phosphatidylinositol-3-kinase; platelet/endothelial cell adhesion molecule; thio-Cl-IB-MECA