Pan S.-L.JIH-HWA GUHPeng C.-Y.Wang S.-W.Chang Y.-L.Cheng F.-C.Chang J.-H.Kuo S.-C.Lee F.-Y.Teng C.-M.2021-06-022021-06-022005223565https://www.scopus.com/inward/record.uri?eid=2-s2.0-23044433522&doi=10.1124%2fjpet.105.085126&partnerID=40&md5=c9197c090b22c56df4ea5007c9dce6f7https://scholars.lib.ntu.edu.tw/handle/123456789/564858Angiogenesis is a process that involves endothelial cell proliferation, migration, invasion, and tube formation, and inhibition of these processes has implications for angiogenesis-mediated disorders. The purpose of this study was to evaluate the antiangiogenic efficacy of YC-1 [3-(5′-hydroxymethyl- 2′-furyl)-1-benzyl indazole] in well characterized in vitro and in vivo systems. YC-1 inhibited the ability of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in a dose-dependent manner to induce proliferation, migration, and tube formation in human umbilical vascular endothelial cells; these outcomes were evaluated using [3H]thymidine incorporation, transwell chamber, and Matrigel-coated slide assays, respectively. YC-1 inhibited VEGF- and bFGF-induced p42/p44 mitogen-activated protein kinase and Akt phosphorylation as well as protein kinase Cα translocation using Western blot analysis. The effect of YC-1 on angiogenesis in vivo was evaluated using the mouse Matrigel implant model. YC-1 administered orally in doses of 1 to 100 mg/kg/day inhibited VEGF- and bFGF-induced neovascularization in a dose-dependent manner over 7 days. These results indicate that YC-1 has antiangiogenic activity at very low doses. Moreover, in transplantable murine tumor models, YC-1 administered orally displayed a high degree of antitumor activity (treatment-to-control life span ratio > 175%) without cytotoxicity. YC-1 may be useful for treating angiogenesis-dependent human diseases such as cancer. Copyright ? 2005 by The American Society for Pharmacology and Experimental Therapeutics.[SDGs]SDG31 benzyl 3 (5 hydroxymethyl 2 furyl)indazole; angiogenic factor; basic fibroblast growth factor; matrigel; mitogen activated protein kinase 1; mitogen activated protein kinase 3; protein kinase B; protein kinase C alpha; tritium; vasculotropin; angiogenesis; animal experiment; animal model; antiangiogenic activity; antineoplastic activity; article; bioassay; cancer therapy; cell function; cell migration; cell proliferation; controlled study; cytotoxicity; DNA synthesis; dose response; endometrium cell; human; human cell; lifespan; low drug dose; mouse; neovascularization (pathology); nonhuman; priority journal; protein phosphorylation; protein transport; tumor model; Western blotting; 1-Phosphatidylinositol 3-Kinase; Angiogenesis Inducing Agents; Angiogenesis Inhibitors; Blotting, Western; Cell Movement; Cell Proliferation; Endothelial Cells; Endothelium, Vascular; Enzyme Activators; Extracellular Signal-Regulated MAP Kinases; Fibroblast Growth Factor 2; Guanylate Cyclase; Humans; Indazoles; Longevity; Microtubules; Neoplasms; Neovascularization, Pathologic; Protein Kinase C; Signal Transduction; Tetrazolium Salts; Thiazoles; Thymidine; Vascular Endothelial Growth Factor Ajournal article10.1124/jpet.105.085126157846552-s2.0-23044433522