PUBLICATION
Anti-angiogenicactivity of a new andrographolide derivative in zebrafish and HUVECs
- Authors
- Li, J., Peng, Y., Li, S., Sun, Y., Chan, J.Y., Cui, G., Wang, D., Zhou, G.C., Lee, S.M.
- ID
- ZDB-PUB-160730-6
- Date
- 2016
- Source
- European Journal of Pharmacology 789: 344-53 (Journal)
- Registered Authors
- Keywords
- Andrographolide, angiogenesis, zebrafish
- MeSH Terms
-
- Angiogenesis Inhibitors/chemistry
- Angiogenesis Inhibitors/pharmacology*
- Angiogenesis Inhibitors/therapeutic use
- Animals
- Cell Line, Tumor
- Cell Movement/drug effects
- Cell Proliferation/drug effects
- Diterpenes/chemistry
- Diterpenes/pharmacology*
- Diterpenes/therapeutic use
- Human Umbilical Vein Endothelial Cells/cytology
- Human Umbilical Vein Endothelial Cells/drug effects*
- Humans
- Neovascularization, Pathologic/drug therapy
- Signal Transduction/drug effects
- Vascular Endothelial Growth Factor A/metabolism
- Zebrafish*
- PubMed
- 27471159 Full text @ Eur. J. Pharmacol.
Citation
Li, J., Peng, Y., Li, S., Sun, Y., Chan, J.Y., Cui, G., Wang, D., Zhou, G.C., Lee, S.M. (2016) Anti-angiogenicactivity of a new andrographolide derivative in zebrafish and HUVECs. European Journal of Pharmacology. 789:344-53.
Abstract
Andrographolide is among the most promising anti-tumor and anti-angiogenic components in Andrographis paniculata but its poor bioavailability and limited efficacy pose difficulties for its therapeutic development. Therefore, improving its pharmaceutical features and potency, by modifying its chemical structure, is desirable. In the present study, a new andrographolide derivative (AGP-40) was synthesized and characterized for its anti-angiogenic properties. Human umbilical vein endothelial cells (HUVECs) and zebrafish models were used to identify the anti-angiogenic activity of AGP-40. AGP-40 significantly suppressed the formation of blood vessels in zebrafish and inhibited proliferation, migration and tube formation in vitro. The anti-angiogenic effects of AGP-40 are at least partially mediated via the PI3K/Akt and MEK/Erk(1/2) signaling pathways. Furthermore, AGP-40 exhibited stronger anti-proliferative effects than andrographolide against A549, HepG2, Hela cancer cell lines. This study is the first to demonstrate the promising anti-angiogenic activity of the new andrographolide derivative AGP-40. Our results indicate that AGP-40 could serve as a potential therapeutic agent for the treatment and prevention of diseases associated with excessive angiogenesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping