Marine compound catunaregin inhibits angiogenesis through the modulation of phosphorylation of akt and eNOS in vivo and in vitro.
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.
Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China. liujxiu@mail.sysu.edu.cn.
Jun-Xiu
JX
Liu
Department of Clinical Laboratory, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China. zhanglmq@sina.com.
Min-Qi
MQ
Luo
Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China. xiameng25@163.com.
Meng
M
Xia
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. wuqi@medmail.com.cn.
Qi
Q
Wu
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. ivylsm@163.com.
Si-Mei
SM
Long
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China. yaohuahu225@aliyun.com.
Yaohua
Y
Hu
Jiaxing University College of Medicine, Jiaxing 314001, China. gaogcjx@163.com.
Guang-Chun
GC
Gao
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. liliyao71@163.com.
Xiao-Li
XL
Yao
Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China. gz87335487@163.net.
Mian
M
He
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China. Huanxingsu@umac.mo.
Huanxing
H
Su
CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China. xiongmingluo@scsio.ac.cn.
Xiong-Ming
XM
Luo
Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China. yaoshuzh@mail.sysu.edu.cn.
Shu-Zhong
SZ
Yao
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D058500:Animal Fins / Q000187:drug effects / Q000254:growth & development; D000818:Animals; D002396:Catechols / Q000737:chemistry / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D004625:Embryo, Nonmammalian; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D017705:Lignans / Q000737:chemistry / Q000494:pharmacology*; D052250:Nitric Oxide Synthase Type III / Q000187:drug effects*; D051058:Oncogene Protein v-akt / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D012038:Regeneration / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015027:Zebrafish
D020533:Angiogenesis Inhibitors; D002396:Catechols; D017705:Lignans; D042461:Vascular Endothelial Growth Factor A; C000593624:catunaregin; D052250:Nitric Oxide Synthase Type III; D051058:Oncogene Protein v-akt