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An andrographolide derivative AGP-26b exhibiting anti-angiogenic activity in HUVECs and zebrafish via blocking the VEGFA/VEGFR2 signaling pathway
Huang B.3; Peng Y.4; Li J.3; Li S.3; Sun Y.4; Wang D.4; Yang B.3; Chan J.Y.-W.3; Yu H.1; Leung G.P.-H.2; Hoi M.P.-M.3; Zhou G.-C.4; Lee S.M.-Y.3
2017
Source PublicationMolecular BioSystems
ISSN17422051 1742206X
Volume13Issue:3Pages:525-536
AbstractThe aim of this study is to investigate the anti-angiogenic properties of andrographolide derivatives AGP-26a (12β-isomer), AGP-26b (12α-isomer) and AGP-26 (4:1 mixture of AGP-26a and AGP-26b) in vitro and in vivo. Human umbilical vein endothelial cells (HUVECs) and the Tg(fli-1a:EGFP)y1 zebrafish model were used to identify the anti-angiogenic activities of AGP-26, AGP-26a, and AGP-26b. The results showed that AGP-26b exhibits the strongest inhibitory effect on VEGF-induced proliferation, migration, invasion and formation of capillary-like structures in HUVECs. In the zebrafish model, AGP-26b also showed the strongest suppression of ISV development. Further studies showed that the underlying mechanism of the anti-angiogenic effects of AGP-26b was at least partly through the blockage of the VEGF/VEGFR2 signaling pathways. AGP-26b blocked the activation of VEGFR2. Consequently, the phosphorylation of key intracellular proangiogenic kinases such as Src family kinase (Src), focal adhesion kinase (Fak), mitogen-activated protein kinase (MEK), extracellular signal-regulated kinase 1 and 2 (Erk1/2) and Akt induced by VEGF was suppressed by treatment with AGP-26b. Moreover, AGP-26b reduced the protein expression of matrix metalloproteinases (MMP-9 but not MMP-2) in HUVECs. These results provide evidence supporting the notion that AGP-26b may serve as a potential therapeutic anti-angiogenic agent.
DOI10.1039/C6MB00641H
URLView the original
Language英語
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Cited Times [WOS]:1   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.Rongene Pharma Co., Ltd.
2.The University of Hong Kong
3.University of Macau
4.Nanjing Tech University
First Author AffilicationUniversity of Macau
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GB/T 7714
Huang B.,Peng Y.,Li J.,et al. An andrographolide derivative AGP-26b exhibiting anti-angiogenic activity in HUVECs and zebrafish via blocking the VEGFA/VEGFR2 signaling pathway[J]. Molecular BioSystems,2017,13(3):525-536.
APA Huang B..,Peng Y..,Li J..,Li S..,Sun Y..,...&Lee S.M.-Y..(2017).An andrographolide derivative AGP-26b exhibiting anti-angiogenic activity in HUVECs and zebrafish via blocking the VEGFA/VEGFR2 signaling pathway.Molecular BioSystems,13(3),525-536.
MLA Huang B.,et al."An andrographolide derivative AGP-26b exhibiting anti-angiogenic activity in HUVECs and zebrafish via blocking the VEGFA/VEGFR2 signaling pathway".Molecular BioSystems 13.3(2017):525-536.
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