title: Prevention of FGF-2-induced angiogenesis by scopoletin, a coumarin compound isolated from Erycibe obtusifolia Benth, and its mechanism of action.
abstract: Previous work in our laboratory has shown that scopoletin, one of the main bioactive constituents of Erycibe obtusifolia Benth stems, exerts anti-arthritic activity in vivo partly by preventing synovial angiogenesis. The present study was performed to further investigate the anti-angiogenic potential of scopoletin, focusing on the mechanisms of action in vitro. In the aortic ring sprouting assay, scopoletin (10, 30 and 100 μM) significantly inhibited the growth of endothelial sprouts in a concentration-dependent manner. As to human umbilical vein endothelial cells (HUVECs), scopoletin could inhibit their proliferation, migration and tubule formation induced by FGF-2, especially the proliferation. It also remarkably decreased the expression of VEGF at mRNA and protein levels, and the phosphorylations of IKKα and IκB but not Akt, as well as the degradation of IκB caused by FGF-2 in HUVECs. These findings suggest that scopoletin is substantially able to attenuate FGF-2-induced angiogenesis, and it might act by directly preventing the stimulation action of FGF-2 and by indirectly decreasing the production of VEGF. Scopoletin down-regulated the VEGF expression through NF-κB rather than PI-3K/Akt signaling pathway.
authors: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, Jiangsu Province, China.
authors: Rong
authors: R
authors: Pan
authors: XingHua
authors: X
authors: Gao
authors: Dan
authors: D
authors: Lu
authors: XianXiang
authors: X
authors: Xu
authors: YuFeng
authors: Y
authors: Xia
authors: Yue
authors: Y
authors: Dai
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010766:Phosphorylation; D051381:Rats; D012603:Scopoletin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D020533:Angiogenesis Inhibitors; D020672:I-kappa B Proteins; D016328:NF-kappa B; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D051550:I-kappa B Kinase; D012603:Scopoletin