PUBLICATION
An andrographolide derivative AGP-26b exhibiting anti-angiogenic activity in HUVECs and zebrafish via blocking the VEGFA/VEGFR2 signaling pathway
- Authors
- Huang, B., Peng, Y., Li, J., Li, S., Sun, Y., Wang, D., Yang, B., Chan, J.Y., Yu, H., Leung, G.P., Hoi, M.P., Zhou, G.C., Lee, S.M.
- ID
- ZDB-PUB-170119-5
- Date
- 2017
- Source
- Molecular Biosystems 13(3): 525-536 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Angiogenesis Inhibitors/chemistry
- Angiogenesis Inhibitors/pharmacology*
- Animals
- Biomarkers
- Cell Movement/drug effects
- Cell Proliferation/drug effects
- Cells, Cultured
- Diterpenes/chemistry
- Diterpenes/pharmacology*
- Human Umbilical Vein Endothelial Cells/drug effects
- Human Umbilical Vein Endothelial Cells/metabolism
- Humans
- Molecular Conformation
- Molecular Structure
- Phosphorylation
- Signal Transduction/drug effects*
- Vascular Endothelial Growth Factor A/metabolism*
- Vascular Endothelial Growth Factor Receptor-2/metabolism*
- Zebrafish
- PubMed
- 28098292 Full text @ Mol. Biosyst.
Citation
Huang, B., Peng, Y., Li, J., Li, S., Sun, Y., Wang, D., Yang, B., Chan, J.Y., Yu, H., Leung, G.P., Hoi, M.P., Zhou, G.C., Lee, S.M. (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.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping