title: CS5931, a novel polypeptide in Ciona savignyi, represses angiogenesis via inhibiting vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs).
abstract: CS5931 is a novel polypeptide from Ciona savignyi with anticancer activities. Previous study in our laboratory has shown that CS5931 can induce cell death via mitochondrial apoptotic pathway. In the present study, we found that the polypeptide could inhibit angiogenesis both in vitro and in vivo. CS5931 inhibited the proliferation, migration and formation of capillary-like structures of HUVECs (Human Umbilical Vein Endothelial Cell) in a dose-dependent manner. Additionally, CS5931 repressed spontaneous angiogenesis of the zebrafish vessels. Further studies showed that CS5931 also blocked vascular endothelial growth factor (VEGF) production but without any effect on its mRNA expression. Moreover, CS5931 reduced the expression of matrix metalloproteinases (MMP-2 and MMP-9) both on protein and mRNA levels in HUVEC cells. We demonstrated that CS5931 possessed strong anti-angiogenic activity both in vitro and in vivo, possible via VEGF and MMPs. This study indicates that CS5931 has the potential to be developed as a novel therapeutic agent as an inhibitor of angiogenesis for the treatment of cancer.
authors.affiliation: Institute of Oceanology, Chinese Academy of Sciences, 7 Nanhai Road, Qingdao 266071, China. liug878@163.com.
authors.forename: Ge
authors.initials: G
authors.lastname: Liu
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China. lmouc@hotmail.com.
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.affiliation: Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, China. Weijt@163.com.
authors.forename: Jianteng
authors.initials: J
authors.lastname: Wei
authors.affiliation: Qingdao University of Science and Technology, Qingdao 266042, China. qkhuanghaijuan@126.com.
authors.forename: Haijuan
authors.initials: H
authors.lastname: Huang
authors.affiliation: Qingdao University of Science and Technology, Qingdao 266042, China. zhangyuyanlcs@163.com.
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Biotechnology, Zhengzhou University, Zhengzhou 450001, China. zhaojinwang2136@126.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Qingdao Agricultural University, Qingdao 266109, China. xiaolin_qd@163.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Institute of Oceanology, Chinese Academy of Sciences, 7 Nanhai Road, Qingdao 266071, China. Wuning2283720@126.com.
authors.forename: Ning
authors.initials: N
authors.lastname: Wu
authors.affiliation: Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266109, China. Zhenglanhong@126.com.
authors.forename: Lanhong
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Pharmacology, Capital Medical University, Beijing 100069, China. linxiukun@yahoo.com.
authors.forename: Xiukun
authors.initials: X
authors.lastname: Lin
mesh_terms: D000469:Alkaline Phosphatase / Q000032:analysis / Q000378:metabolism; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004396:Coloring Agents; D004625:Embryo, Nonmammalian / Q000187:drug effects; D005260:Female; D000077155:Granulins; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology*; D020782:Matrix Metalloproteinases / Q000096:biosynthesis; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000737:chemistry; D013778:Tetrazolium Salts; D013844:Thiazoles; D014470:Umbilical Cord / Q000187:drug effects / Q000254:growth & development; D014561:Urochordata / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D015027:Zebrafish
chemical_list: D020533:Angiogenesis Inhibitors; D004396:Coloring Agents; D000077155:Granulins; D036341:Intercellular Signaling Peptides and Proteins; D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D011994:Recombinant Proteins; D013778:Tetrazolium Salts; D013844:Thiazoles; D042461:Vascular Endothelial Growth Factor A; D000469:Alkaline Phosphatase; D020782:Matrix Metalloproteinases; C022616:thiazolyl blue