Andrographolide inhibits tumor angiogenesis via blocking VEGFA/VEGFR2-MAPKs signaling cascade.

Abstract

Traditional medicinal herb Andrographis paniculata is known to possess anti-tumor activity, and its potential active compound is the diterpenoid lactone andrographolide (ANGL). In this study, we have found that ANGL inhibits tumor growth in nude mice bearing xenografted Hep3B cancer cells, concomitant with a reduction in tumor vessel counts. ANGL inhibits vascular endothelial growth factor A (VEGFA)-induced angiogenic responses in vitro and neoangiogenesis in vivo. We also found that ANGL inhibits VEGFA-induced phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2) and its downstream targets such as the mitogen-activated protein kinases (MAPKs). ANGL interferes with the binding of VEGFA to VEGFR2, but has no effect on VEGFR2 kinase activity in vitro. Taken together, our results indicate that ANGL possesses anti-angiogenic activity which is mediated by preventing VEGFA-induced phosphorylation and activation of VEGFR2 and MAPKs. The present study indicates that ANGL can block tumor angiogenesis and therefore represents therapeutic potential for cancer treatment.

• Authors: Kaikai Shen, Lili Ji, Bin Lu, Chong Xu, Chenyuan Gong, Grant Morahan, Zhengtao Wang
• Journal: Chemico-biological interactions (Chem Biol Interact) Vol. 218 Pg. 99-106 (Jul 25 2014) ISSN: 1872-7786 [Electronic] Ireland
• PMID: 24814888 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Angiogenesis Inhibitors
• Diterpenes
• Vascular Endothelial Growth Factor A
• andrographolide
• Vascular Endothelial Growth Factor Receptor-2
• Mitogen-Activated Protein Kinases

Topics

• Angiogenesis Inhibitors (chemistry, pharmacology, therapeutic use)
• Animals
• Cell Survival (drug effects)
• Cells, Cultured
• Diterpenes (chemistry, pharmacology, therapeutic use)
• Human Umbilical Vein Endothelial Cells
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Nude
• Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism)
• Models, Animal
• Molecular Structure
• Neovascularization, Pathologic (drug therapy)
• Protein Binding (drug effects)
• Signal Transduction (drug effects)
• Vascular Endothelial Growth Factor A (antagonists & inhibitors)
• Vascular Endothelial Growth Factor Receptor-2 (antagonists & inhibitors, metabolism)