title: KR-31831, benzopyran derivative, inhibits VEGF-induced angiogenesis of HUVECs through suppressing KDR expression.
abstract: Angiogenesis is important in the development and progression of cancer, therefore the therapeutic approach based on anti-angiogenesis may represent a promising therapeutic option. KR-31831 is a novel anti-ischemic agent. Previously, we reported the anti-angiogenic activity of KR-31831. In the present study we investigated the molecular mechanisms underlying anti-angiogenic activity of KR-31831. We show that KR-31831 inhibits vascular endothelial growth factor (VEGF)-induced proliferation and tube formation via release of intracellular Ca2+ and phosphorylation of extra-cellular regulated kinase 1/2 (Erk 1/2) in human umbilical vein endothelial cells (HUVECs). Moreover, the expression of VEGF receptor 2 (VEGFR2, known as Flk-1 or KDR) was reduced by the treatment of KR-31831. These results suggest that KR-31831 may have inhibitory effects on tumor angiogenesis through down-regulation of KDR expression.
authors.affiliation: Department of Molecular Biology, Pusan National University, Busan 609-735, Korea.
authors.forename: Shi-Young
authors.initials: SY
authors.lastname: Park
authors.forename: Eun-Hee
authors.initials: EH
authors.lastname: Seo
authors.forename: Hyun Seok
authors.initials: HS
authors.lastname: Song
authors.forename: Seung-Youn
authors.initials: SY
authors.lastname: Jung
authors.forename: Young-Kyoung
authors.initials: YK
authors.lastname: Lee
authors.forename: Kyu-Yang
authors.initials: KY
authors.lastname: Yi
authors.forename: Sung-Eun
authors.initials: SE
authors.lastname: Yoo
authors.forename: Yung-Jin
authors.initials: YJ
authors.lastname: Kim
mesh_terms: D001578:Benzopyrans / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D015151:Immunoblotting; D007797:Laminin / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D010766:Phosphorylation; D011509:Proteoglycans / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014471:Umbilical Veins / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001578:Benzopyrans; D004338:Drug Combinations; D007093:Imidazoles; C503693:KR 31831; D007797:Laminin; D011509:Proteoglycans; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C059485:matrigel; D003094:Collagen; D040301:Vascular Endothelial Growth Factor Receptor-2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3