PUBLICATION
AGS-30, an andrographolide derivative, suppresses tumor angiogenesis and growth in vitro and in vivo
- Authors
- Li, J., Li, F., Tang, F., Zhang, J., Li, R., Sheng, D., Lee, S.M., Zhou, G.C., Leung, G.P.
- ID
- ZDB-PUB-191111-20
- Date
- 2019
- Source
- Biochemical pharmacology 171: 113694 (Journal)
- Registered Authors
- Keywords
- Andrographolide derivative, Anti-angiogenic, Colon cancer, VEGF
- MeSH Terms
-
- Angiogenesis Inhibitors/chemistry
- Angiogenesis Inhibitors/pharmacology*
- Animals
- Animals, Genetically Modified
- Cells, Cultured
- Diterpenes/chemistry
- Diterpenes/pharmacology*
- Embryo, Nonmammalian/blood supply
- Embryo, Nonmammalian/drug effects*
- Embryo, Nonmammalian/embryology
- HT29 Cells
- Human Umbilical Vein Endothelial Cells/drug effects*
- Human Umbilical Vein Endothelial Cells/metabolism
- Humans
- Male
- Mice, Inbred C57BL
- Mice, Nude
- Molecular Structure
- Neovascularization, Pathologic/prevention & control*
- Rats, Sprague-Dawley
- Xenograft Model Antitumor Assays/methods
- Zebrafish/embryology*
- Zebrafish/genetics
- PubMed
- 31706845 Full text @ Biochem. Pharmacol.
Citation
Li, J., Li, F., Tang, F., Zhang, J., Li, R., Sheng, D., Lee, S.M., Zhou, G.C., Leung, G.P. (2019) AGS-30, an andrographolide derivative, suppresses tumor angiogenesis and growth in vitro and in vivo. Biochemical pharmacology. 171:113694.
Abstract
Poor bioavailability and limited efficacy are challenges associated with using andrographolide as a therapeutic agent. We recently synthesized AGS-30, a new andrographolide derivative, in our laboratory. In this study we investigated the potential anti-tumor effect of AGS-30 and the underlying mechanisms, particularly those related to angiogenesis. Results from our in vitro experiments showed that AGS-30 exerted anti-angiogenic effects by inhibiting endothelial cell proliferation, migration, invasion, and tube formation. Phosphorylation and activation of angiogenesis-related signaling molecules (e.g., vascular endothelial growth factor [VEGF] receptor 2, mitogen-activated protein kinase kinase 1/2, extracellular signal-regulated kinase 1/2, mechanistic target of rapamycin [mTOR], protein kinase B [Akt], and p38) were markedly reduced by AGS-30. Meanwhile, AGS-30 potently inhibited cell proliferation and phosphorylation of cell survival-related proteins (e.g., Akt, mTOR, and ERK1/2) and decreased the expression of VEGF in HT-29 colon cancer cells. AGS-30 blocked microvessel sprouting in a rat aortic ring model and blood vessel formation in zebrafish embryos and a mouse Matrigel plug model. Additionally, AGS-30 suppressed tumor growth and angiogenesis in HT-29 colon cancer cell xenografts in nude mice. These effects were not observed when same concentration of andrographolide, the parent compound of AGS-30, was used. Thus, AGS-30 exerted a strong antitumor effect by inhibiting tumor cell growth and angiogenesis and is a candidate compound for the treatment of cancer.
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