UM
An andrographolide derivative AGP-26b exibitiing anti-angiogenic activity in HUVECs and zebrafish via blocking the VEGFA/VEGFR2 signaling pathway
Huang, Bin; Peng, Yuran; Li, Jingjing; Li, Shang; Sun, Yicheng; Wang, Decai; Yang, Binrui; Chan, Judy Yuet-Wa; Yu, Huidong; Leung, George Pak-Heng; Hoi, Maggie Pui-Man; Zhou, Guo-Chun; Lee, Simon Ming-Yuen
2017-03
Source PublicationMOLECULAR BIOSYSTEMS
ISSN1742-206X
Volume13Issue:3Pages:525-536
AbstractThe aim of this study is to investigate the anti-angiogenic properties of andrographolide derivatives AGP-26a (12 beta-isomer), AGP-26b (12 alpha-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
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemistry & Molecular Biology
WOS IDWOS:000395894400009
PublisherROYAL SOC CHEMISTRY
The Source to ArticleWOS
Citation statistics
Document TypeJournal article
CollectionUniversity of Macau
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GB/T 7714
Huang, Bin,Peng, Yuran,Li, Jingjing,et al. An andrographolide derivative AGP-26b exibitiing anti-angiogenic activity in HUVECs and zebrafish via blocking the VEGFA/VEGFR2 signaling pathway[J]. MOLECULAR BIOSYSTEMS,2017,13(3):525-536.
APA Huang, Bin.,Peng, Yuran.,Li, Jingjing.,Li, Shang.,Sun, Yicheng.,...&Lee, Simon Ming-Yuen.(2017).An andrographolide derivative AGP-26b exibitiing anti-angiogenic activity in HUVECs and zebrafish via blocking the VEGFA/VEGFR2 signaling pathway.MOLECULAR BIOSYSTEMS,13(3),525-536.
MLA Huang, Bin,et al."An andrographolide derivative AGP-26b exibitiing 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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