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

• Published in: Molecular nutrition & food research 2013-02, Vol.57 (2), p.225-234
• Main Authors: Lee, Sun H., Lee, Jongkook, Jung, Myung H., Lee, You M.
• Format: Article
• Language: English
• Subjects: Angiogenesis inhibitor; Angiogenesis Inhibitors - pharmacology; Animals; Antineoplastic Agents - pharmacology; bFGF; Biological and medical sciences; Blotting, Western; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - drug effects; Chick Embryo; Fibroblast Growth Factor 2 - antagonists & inhibitors; Fibroblast Growth Factor 2 - genetics; Fibroblast Growth Factor 2 - metabolism; Food industries; Fundamental and applied biological sciences. Psychology; Glyceollins; Glycine max - chemistry; Human Umbilical Vein Endothelial Cells; Humans; Immunohistochemistry; JNK Mitogen-Activated Protein Kinases - genetics; JNK Mitogen-Activated Protein Kinases - metabolism; Mice; Mice, Inbred C57BL; Neovascularization, Pathologic - prevention & control; p38 Mitogen-Activated Protein Kinases - genetics; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphorylation; Phytoalexins; Plant Extracts - pharmacology; Pterocarpans - isolation & purification; Pterocarpans - pharmacology; Receptor, Fibroblast Growth Factor, Type 1 - genetics; Receptor, Fibroblast Growth Factor, Type 1 - metabolism; Sesquiterpenes - isolation & purification; Sesquiterpenes - pharmacology; Signal Transduction; Signaling pathway; Vascular Endothelial Growth Factor A - antagonists & inhibitors; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; Vascular Endothelial Growth Factor Receptor-2 - genetics; Vascular Endothelial Growth Factor Receptor-2 - metabolism; VEGF; Zebrafish - growth & development
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.201200489

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.