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Issue 3, 2017
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An andrographolide derivative AGP-26b exhibiting anti-angiogenic activity in HUVECs and zebrafish via blocking the VEGFA/VEGFR2 signaling pathway

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Abstract

The 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.

Graphical abstract: An andrographolide derivative AGP-26b exhibiting anti-angiogenic activity in HUVECs and zebrafish via blocking the VEGFA/VEGFR2 signaling pathway

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Publication details

The article was received on 09 Sep 2016, accepted on 29 Dec 2016 and first published on 05 Jan 2017


Article type: Paper
DOI: 10.1039/C6MB00641H
Mol. BioSyst., 2017,13, 525-536

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    An andrographolide derivative AGP-26b exhibiting anti-angiogenic activity in HUVECs and zebrafish via blocking the VEGFA/VEGFR2 signaling pathway

    B. Huang, Y. Peng, J. Li, S. Li, Y. Sun, D. Wang, B. Yang, J. Y. Chan, H. Yu, G. P. Leung, M. P. Hoi, G. Zhou and S. M. Lee, Mol. BioSyst., 2017, 13, 525
    DOI: 10.1039/C6MB00641H

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