Glyceollins, a novel class of soy phytoalexins, inhibit angiogenesis by blocking the VEGF and bFGF signaling pathways.

Abstract

SCOPE:

Glyceollins are a novel class of soybean phytoalexins with potential cancer-preventive and antiestrogenic effects. The angiogenic cascade during tumor development consists of the release of angiogenic factors and binding of angiogenic factors to receptors on endothelial cells to activate downstream signaling pathways. However, the potential medicinal value of glyceollins, especially in antiangiogenesis, remains unexplored.

METHODS AND RESULTS:

Here, we investigated the antiangiogenic activity of glyceollins and their underlying mechanisms. Glyceollins inhibited vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF) induced in vitro angiogenic activity. Glyceollins inhibited VEGF receptor-2 or FGF receptor-1 activity and their downstream signaling pathways such as extracellular regulated kinase 1/2, c-Jun N-terminal kinase, as well as p38 mitogen-activated protein kinase and focal adhesion kinase induced by VEGF or bFGF. Glyceollins significantly suppressed VEGF receptor-2 kinase activity assayed by the ELISA. Glyceollins significantly attenuated in vivo and ex vivo microvessel development in a dose-dependent manner and tumor growth by suppressing microvessel density in Lewis lung carcinoma (LLC) mouse xenograft.

CONCLUSION:

Thus, glyceollins, elicited ingredients of soy source, target the signaling pathways mediated by VEGF or bFGF, providing new perspectives into potential therapeutics for preventing and treating hypervascularized diseases including cancer.

• Authors: Sun H Lee, Jongkook Lee, Myung H Jung, You M Lee
• Journal: Molecular nutrition & food research (Mol Nutr Food Res) Vol. 57 Issue 2 Pg. 225-34 (Feb 2013) ISSN: 1613-4133 [Electronic] Germany
• PMID: 23229497 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Angiogenesis Inhibitors
• Antineoplastic Agents
• Plant Extracts
• Pterocarpans
• Sesquiterpenes
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• Fibroblast Growth Factor 2
• glyceollin
• Receptor, Fibroblast Growth Factor, Type 1
• Vascular Endothelial Growth Factor Receptor-2
• JNK Mitogen-Activated Protein Kinases
• p38 Mitogen-Activated Protein Kinases
• Phytoalexins

Topics

• Angiogenesis Inhibitors (pharmacology)
• Animals
• Antineoplastic Agents (pharmacology)
• Blotting, Western
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Chick Embryo
• Fibroblast Growth Factor 2 (antagonists & inhibitors, genetics, metabolism)
• Human Umbilical Vein Endothelial Cells
• Humans
• Immunohistochemistry
• JNK Mitogen-Activated Protein Kinases (genetics, metabolism)
• Mice
• Mice, Inbred C57BL
• Neovascularization, Pathologic (prevention & control)
• Phosphorylation
• Plant Extracts (pharmacology)
• Pterocarpans (isolation & purification, pharmacology)
• Receptor, Fibroblast Growth Factor, Type 1 (genetics, metabolism)
• Sesquiterpenes (isolation & purification, pharmacology)
• Signal Transduction
• Soybeans (chemistry)
• Vascular Endothelial Growth Factor A (antagonists & inhibitors, genetics, metabolism)
• Vascular Endothelial Growth Factor Receptor-2 (genetics, metabolism)
• Zebrafish (growth & development)
• p38 Mitogen-Activated Protein Kinases (genetics, metabolism)
• Phytoalexins