title: Inhibition of vascular endothelial growth factor-induced angiogenesis by scopoletin through interrupting the autophosphorylation of VEGF receptor 2 and its downstream signaling pathways.
abstract: Our previous studies revealed that scopoletin, the main bioactive constituent of Erycibe obtusifolia Benth stems, exerted anti-arthritic activity in vivo partly by preventing synovial angiogenesis. Herein we further investigated the anti-angiogenic potential and related mechanisms of this coumarin compound in vivo and in vitro. On chick chorioallantoic membrane (CAM) model, scopoletin (10, 30, 100 nmol/egg) dose-dependently reduced the blood vessels that were quantified by counting the number of blood vessel branch points. In vitro, scopoletin at concentrations above 30 microM obviously inhibited the VEGF-induced tube formation, proliferation and migration of human umbilical vein endothelial cells (HUVECs). Furthermore, scopoletin was shown to block VEGF-induced autophosphorylation of VEGFR2 but not VEGFR1, and down-regulate the following activation of ERK1/2, p38 MAPK and endothelial nitric oxide synthase (eNOS) as well as the production of nitric oxide (NO) in HUVECs. In sum, our findings further support that scopoletin is a candidate of angiogenesis inhibitors, and it functions by interrupting the autophosphorylation of VEGF receptor 2 (VEGFR2) and the downstream signaling pathways.
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, Jiangsu Province, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Pan
authors.forename: Yue
authors.initials: Y
authors.lastname: Dai
authors.forename: Xing-Hua
authors.initials: XH
authors.lastname: Gao
authors.forename: Dan
authors.initials: D
authors.lastname: Lu
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Xia
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control; D009569:Nitric Oxide / Q000378:metabolism; D010766:Phosphorylation; D012603:Scopoletin / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D014471:Umbilical Veins; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D040301:Vascular Endothelial Growth Factor Receptor-2; D012603:Scopoletin