title: γ-Tocotrienol inhibits angiogenesis of human umbilical vein endothelial cell induced by cancer cell.
abstract: Antiangiogenic therapy mediated by food components is an established strategy for cancer chemoprevention. Growth factors play critical roles in tumor angiogenesis. A conditioned medium containing growth factors from human gastric adenocarcinoma SGC-7901 cell conditioned medium was used as an angiogenic stimulus in this study. The purpose of this study was to evaluate the inhibitory effect and possible mechanism of γ-tocotrienol on tumor angiogenesis. The results showed that γ-tocotrienol (10-40 μmol/L) significantly suppressed proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVECs) induced by SGC-7901 cell conditioned medium in a dose-dependent manner. γ-Tocotrienol (800-1200 μg/egg) also inhibited new blood vessel formation on the growing chick embryo chorioallantoic membrane in a dose-dependent manner. Moreover, the inhibitory effects of γ-tocotrienol on HUVECs were correlated with inducing the apoptosis and arresting cell cycle at the G(0)/G(1) phase at a dose of 40 μmol/L γ-tocotrienol. In addition, γ-tocotrienol inhibited angiogenesis in HUVECs by down-regulation of β-catenin, cyclin D1, CD44, phospho-VEGFR-2 and MMP-9. The antiangiogenic effects of γ-tocotrienol on HUVECs may be attributable to regulation of Wnt signaling by decreasing β-catenin expression. Thus, our results suggest that γ-tocotrienol has a potential chemopreventive agent via antiangiogenesis.
authors.affiliation: Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin 150081, People's Republic of China. liyang820119@sohu.com
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Wen-Guang
authors.initials: WG
authors.lastname: Sun
authors.forename: Hui-Kun
authors.initials: HK
authors.lastname: Liu
authors.forename: Gui-Yun
authors.initials: GY
authors.lastname: Qi
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Xiang-Rong
authors.initials: XR
authors.lastname: Sun
authors.forename: Bing-Qing
authors.initials: BQ
authors.lastname: Chen
authors.forename: Jia-Ren
authors.initials: JR
authors.lastname: Liu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018890:Chemoprevention; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology* / Q000627:therapeutic use; D015536:Down-Regulation; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D046529:Microscopy, Electron, Transmission; D009369:Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000517:prevention & control; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D015398:Signal Transduction; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D002839:Chromans; D051176:beta Catenin; D014810:Vitamin E; C013649:plastochromanol 8; D040301:Vascular Endothelial Growth Factor Receptor-2