Premium
Glyceollins, a novel class of soy phytoalexins, inhibit angiogenesis by blocking the VEGF and b FGF signaling pathways
Author(s) -
Lee Sun H.,
Lee Jongkook,
Jung Myung H.,
Lee You M.
Publication year - 2013
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201200489
Subject(s) - angiogenesis , vascular endothelial growth factor , fibroblast growth factor , signal transduction , cancer research , kinase , pharmacology , chemistry , protein kinase a , receptor , microbiology and biotechnology , endocrinology , medicine , biology , biochemistry , vegf receptors
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 (b FGF ) 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 b FGF . 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 b FGF , providing new perspectives into potential therapeutics for preventing and treating hypervascularized diseases including cancer.