title: A fucoidan from Nemacystus decipiens disrupts angiogenesis through targeting bone morphogenetic protein 4.
abstract: A sulfated and acetylated fucoidan, named NDH01, was extracted from seaweed Nemacystus decipiens. NDH01 was composed of mannose, glucuronic acid, fucose, sulfate group and acetyl group in the molar ratio of 3.0: 14.4: 82.6: 34.3: 13.9. The backbone of NDH01 was fucose-free core, composed of α-d-1,2-Manp and β-d-1,4-GlcpA disaccharide repeat unit. The branches were attached at the C3, C4 and C6 of α-d-1,2-Manp. The sidechain was composed of α-l-1,3,4-Fucp, α-l-1,4-Fucp, α-l-1,3-Fucp and α-l-1,4-GlcpA. The sulfate group was linked to C4 of α-l-1,3,4-Fucp, whereas, acetyl group was branched on C2 of α-l-1,2,3-Fucp. NDH01 could disrupt tube formation and inhibit the migration as well as cell growth of human microvascular endothelial cells. Besides, phosphorylation of Smad/1/5/8, Erk and FAK was significantly inhibited by NDH01. Further studies uncovered that NDH01 blocked Smad1/5/8 signaling via interacting with bone morphogenetic protein 4 and downregulating bone morphogenetic protein 4 expression. The results suggested that NDH01 might be an angiogenesis inhibitor through targeting bone morphogenetic protein 4.
authors.affiliation: Glycochemistry and Glycobiology Lab., Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China.
authors.forename: Wucheng
authors.initials: W
authors.lastname: Wang
authors.affiliation: Glycochemistry and Glycobiology Lab., Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China.
authors.forename: Huanjun
authors.initials: H
authors.lastname: Chen
authors.affiliation: Glycochemistry and Glycobiology Lab., Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Glycochemistry and Glycobiology Lab., Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Glycochemistry and Glycobiology Lab., Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China.
authors.forename: Qifei
authors.initials: Q
authors.lastname: Cong
authors.affiliation: Glycochemistry and Glycobiology Lab., Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China.
authors.forename: Peipei
authors.initials: P
authors.lastname: Wang
authors.affiliation: Glycochemistry and Glycobiology Lab., Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China. Electronic address: dingkan@simm.ac.cn.
authors.forename: Kan
authors.initials: K
authors.lastname: Ding
mesh_terms: D020533:Angiogenesis Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism*; D002240:Carbohydrate Sequence; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D010766:Phosphorylation / Q000187:drug effects; D011134:Polysaccharides / Q000302:isolation & purification / Q000494:pharmacology*; D012624:Seaweed / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D055415:Bone Morphogenetic Protein 4; D011134:Polysaccharides; D051785:Smad Proteins; C007789:fucoidan; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Anti-angiogenic activity; Bone morphogenetic protein 4; Fucoidan; Nemacystus decipiens; Structure