title: 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.
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.
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Qi
authors.affiliation: Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Liu
authors.affiliation: Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Qiu
authors.affiliation: Department of Pharmacology, Capital Medical University, Beijing 100069, China.
authors.forename: Xiukun
authors.initials: X
authors.lastname: Lin
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China. Electronic address: lmouc@ouc.edu.cn.
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D002396:Catechols / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004987:Ethers / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D002396:Catechols; D004987:Ethers; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C583604:Vegfaa protein, zebrafish; D029961:Zebrafish Proteins; C000601939:bis(2,3-dibromo-4,5-dihydroxybenzyl) ether; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: Antiangiogenesis; Bis(2,3-dibromo-4,5-dihydroxybenzyl) ether; VEGF; VEGFR; Zebrafish