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Mar. Drugs 2014, 12(3), 1530-1544; doi:10.3390/md12031530

CS5931, a Novel Polypeptide in Ciona savignyi, Represses Angiogenesis via Inhibiting Vascular Endothelial Growth Factor (VEGF) and Matrix Metalloproteinases (MMPs)

3,* , 4
1 Institute of Oceanology, Chinese Academy of Sciences, 7 Nanhai Road, Qingdao 266071, China 2 The University of Chinese Academy of Sciences, Beijing 100049, China 3 Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China 4 Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, China 5 Qingdao University of Science and Technology, Qingdao 266042, China 6 Department of Biotechnology, Zhengzhou University, Zhengzhou 450001, China 7 Qingdao Agricultural University, Qingdao 266109, China 8 Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China 9 Department of Pharmacology, Capital Medical University, Beijing 100069, China
* Authors to whom correspondence should be addressed.
Received: 15 November 2013 / Revised: 9 January 2014 / Accepted: 22 January 2014 / Published: 13 March 2014
(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)
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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.
Keywords: CS5931; anti-angiogenesis; zebrafish; HUVECs; VEGF and MMPs CS5931; anti-angiogenesis; zebrafish; HUVECs; VEGF and MMPs
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Liu, G.; Liu, M.; Wei, J.; Huang, H.; Zhang, Y.; Zhao, J.; Xiao, L.; Wu, N.; Zheng, L.; Lin, X. CS5931, a Novel Polypeptide in Ciona savignyi, Represses Angiogenesis via Inhibiting Vascular Endothelial Growth Factor (VEGF) and Matrix Metalloproteinases (MMPs). Mar. Drugs 2014, 12, 1530-1544.

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