Marine bromophenol bis(2,3-dibromo-4,5-dihydroxybenzyl) ether, represses angiogenesis in HUVEC cells and in zebrafish embryos via inhibiting the VEGF signal systems

Biomed Pharmacother. 2015 Oct:75:58-66. doi: 10.1016/j.biopha.2015.08.033. Epub 2015 Sep 7.

Abstract

Bis(2,3-dibromo-4,5-dihydroxybenzyl) ether (BDDE) is a bromophenol compound derived from marine algae. Our previous reports have shown that BDDE possessed anticancer activity in vitro. However, its antiangiogenesis activity and possible mechanisms remain unclear. The present study demonstrated that BDDE displayed in vitro antiangiogenesis capabilities by significantly inhibiting HUVEC cells proliferation, migration, and tube formation, without any effect on the preformed vascular tube. Western blot analysis revealed that BDDE decreased the protein level of VEGF and VEGFR but not that of EGFR, FGFR, and IGFR. In addition, BDDE inactivated the VEGF downstream signaling molecules including mTOR and Src, whereas activated Akt and ERK. Moreover, BDDE blocked subintestinal vessel formation in zebrafish embryos in vivo and showed toxicity under high concentrations of BDDE. The results of this present study indicated that BDDE, which has unique chemical structure different from current antiangiogenesis agents, could be used as a potential drug candidate for cancer prevention and therapy.

Keywords: Antiangiogenesis; Bis(2,3-dibromo-4,5-dihydroxybenzyl) ether; VEGF; VEGFR; Zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Catechols / pharmacology*
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Ethers / pharmacology*
  • Human Umbilical Vein Endothelial Cells / drug effects*
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Neovascularization, Physiologic / drug effects*
  • Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors
  • Receptors, Vascular Endothelial Growth Factor / metabolism
  • S Phase Cell Cycle Checkpoints / drug effects
  • Signal Transduction / drug effects*
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor A / metabolism
  • Zebrafish / embryology
  • Zebrafish / metabolism*
  • Zebrafish Proteins / antagonists & inhibitors*
  • Zebrafish Proteins / metabolism

Substances

  • Angiogenesis Inhibitors
  • Catechols
  • Ethers
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Vegfaa protein, zebrafish
  • Zebrafish Proteins
  • bis(2,3-dibromo-4,5-dihydroxybenzyl) ether
  • Receptors, Vascular Endothelial Growth Factor