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Mar. Drugs 2014, 12(5), 2790-2801; doi:10.3390/md12052790

Marine Compound Catunaregin Inhibits Angiogenesis through the Modulation of Phosphorylation of Akt and eNOS in vivo and in vitro

, 2,†
, 1
, 3
, 3
, 4
, 5
, 3
, 1
, 4
, 6,*  and 1,*
1 Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China 2 Department of Clinical Laboratory, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China 3 Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China 4 State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China 5 Jiaxing University College of Medicine, Jiaxing 314001, China 6 CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China These two authors contributed equally to the work.
* Authors to whom correspondence should be addressed.
Received: 10 February 2014 / Revised: 9 April 2014 / Accepted: 14 April 2014 / Published: 12 May 2014
(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)
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Angiogenesis is the formation of blood vessels from pre-existing vasculature. Excessive or uncontrolled angiogenesis is a major contributor to many pathological conditions whereas inhibition of aberrant angiogenesis is beneficial to patients with pathological angiogenesis. Catunaregin is a core of novel marine compound isolated from mangrove associate. The potential anti-angiogenesis of catunaregin was investigated in human umbilical vein endothelial cells (HUVECs) and zebrafish. HUVECs were treated with different concentrations of catunaregin in the presence or absence of VEGF. The angiogenic phenotypes including cell invasion cell migration and tube formation were evaluated following catunaregin treatment in HUVECs. The possible involvement of AKT, eNOS and ERK1/2 in catunaregin-induced anti-angiogenesis was explored using Western blotting. The anti-angiogenesis of catunaregin was further tested in the zebrafish embryo neovascularization and caudal fin regeneration assays. We found that catunaregin dose-dependently inhibited angiogenesis in both HUVECs and zebrafish embryo neovascularization and zebrafish caudal fin regeneration assays. In addition, catunaregin significantly decreased the phosphorylation of Akt and eNOS, but not the phosphorylation of ERK1/2. The present work demonstrates that catunaregin exerts the anti-angiogenic activity at least in part through the regulation of the Akt and eNOS signaling pathways.
Keywords: anti-angiogenesis; catunaregin; VEGF; zebrafish; HUVECs anti-angiogenesis; catunaregin; VEGF; zebrafish; HUVECs
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Liu, J.-X.; Luo, M.-Q.; Xia, M.; Wu, Q.; Long, S.-M.; Hu, Y.; Gao, G.-C.; Yao, X.-L.; He, M.; Su, H.; Luo, X.-M.; Yao, S.-Z. Marine Compound Catunaregin Inhibits Angiogenesis through the Modulation of Phosphorylation of Akt and eNOS in vivo and in vitro. Mar. Drugs 2014, 12, 2790-2801.

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