title: Anti-angiogenic effect of furanodiene on HUVECs in vitro and on zebrafish in vivo.
abstract: BACKGROUND
  Furanodiene is an active ingredient of the traditional Chinese medicine, Rhizoma Curcumae, commonly used for the treatment of cancer in China.
  
  
  OBJECTIVE
  To investigate the anti-cancer property of Rhizoma Curcumae, this study describes the anti-angiogenic activities of furanodiene in human umbilical vein endothelial cells (HUVECs) in vitro and in zebrafish in vivo.
  
  
  METHODS
  HUVECs were treated with different doses of furanodiene in the presence or absence of vascular endothelial growth factor (VEGF). The anti-proliferative effect of furanodiene was measured using the XTT assay. The anti-migration and anti-invasion activities of this compound were investigated with a wound-healing migration model and a three-dimensional cell invasion model, respectively. The effects of furanodiene on HUVEC differentiation were assessed by in vitro tube formation in Matrigel™. The expression of related proteins was detected by Western blot. Morphological observations of zebrafish were evaluated in transgenic Tg (fli1: EGFP) zebrafish embryos.
  
  
  RESULTS
  Our results showed that furanodiene exposure could significantly inhibit the proliferation of HUVECs in a dose-dependent manner and inhibit VEGF-induced proliferation at a low dose. Relative to the VEGF-induced control, the number of invading and migrating cells was significantly reduced in the furanodiene-treated groups. Furanodiene also dramatically suppressed tube formation and p-Akt (Ser473), p-Erk 1/2 (Thr202/Tyr204), ICAM-1, p-p85 (Ser428) as well as p85 protein expression. Furthermore, exposure to furanodiene inhibited angiogenesis in the zebrafish model.
  
  
  CONCLUSIONS
  This study demonstrated that furanodiene exposure exhibits a potential anti-angiogenic effect through suppression of endothelial cell growth, invasion, migration and tube formation via regulation of the PI3K pathway. This potential anti-angiogenic effect of furanodiene may play an important role in the anti-tumor activity of the traditional Chinese medicine, Rhizoma Curcumae.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau, China.
authors.forename: Zhang-Feng
authors.initials: ZF
authors.lastname: Zhong
authors.forename: Pui-Man
authors.initials: PM
authors.lastname: Hoi
authors.forename: Guo-Sheng
authors.initials: GS
authors.lastname: Wu
authors.forename: Zeng-Tao
authors.initials: ZT
authors.lastname: Xu
authors.forename: Wen
authors.initials: W
authors.lastname: Tan
authors.forename: Xiu-Ping
authors.initials: XP
authors.lastname: Chen
authors.forename: Liao
authors.initials: L
authors.lastname: Cui
authors.forename: Tie
authors.initials: T
authors.lastname: Wu
authors.forename: Yi-Tao
authors.initials: YT
authors.lastname: Wang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D030801:Animals, Genetically Modified; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D058543:Class Ia Phosphatidylinositol 3-Kinase / Q000378:metabolism; D030024:Curcuma / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology*; D005663:Furans / Q000302:isolation & purification / Q000494:pharmacology*; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006574:Heterocyclic Compounds, 2-Ring / Q000302:isolation & purification / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008516:Medicine, Chinese Traditional; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010766:Phosphorylation; D010946:Plants, Medicinal; D051789:Proto-Oncogene Protein c-fli-1 / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012694:Serine; D015398:Signal Transduction / Q000187:drug effects; D013912:Threonine; D014443:Tyrosine; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D005663:Furans; D006574:Heterocyclic Compounds, 2-Ring; D051789:Proto-Oncogene Protein c-fli-1; D042461:Vascular Endothelial Growth Factor A; C485184:enhanced green fluorescent protein; D018799:Intercellular Adhesion Molecule-1; D049452:Green Fluorescent Proteins; C442489:furanodiene; D013912:Threonine; D014443:Tyrosine; D012694:Serine; D058543:Class Ia Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3