Capsiate, a nonpungent capsaicin-like compound, inhibits angiogenesis and vascular permeability via a direct inhibition of Src kinase activity

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Title
Capsiate, a nonpungent capsaicin-like compound, inhibits angiogenesis and vascular permeability via a direct inhibition of Src kinase activity
Author(s)
B J Pyun; S Choi; Y Lee; T W Kim; Jeong Ki Min; Y Kim; B D Kim; J H Kim; T Y Kim; Y M Kim; Y G Kwon
Bibliographic Citation
Cancer Research, vol. 68, no. 1, pp. 227-235
Publication Year
2008
Abstract
Capsiate, a nonpungent capsaicin analogue, and its dihydroderivative dihydrocapsiate are the major capsaicinoids of the nonpungent red pepper cultivar CH-19 Sweet. In this study, we report the biological actions and underlying molecular mechanisms of capsiate on angiogenesis and vascular permeability. In vitro, capsiate and dihydrocapsiate inhibited vascular endothelial growth factor (VEGF)-induced proliferation, chemotactic motility, and capillary-like tube formation of primary cultured human endothelial cells. They also inhibited sprouting of endothelial cells in the rat aorta and formation of new blood vessels in the mouse Matrigel plug assay in response to VEGF. Moreover, both compounds blocked VEGF-induced endothelial permeability and loss of vascular endothelial (VE)-cadherin-facilitated endothelial cell-cell junctions. Importantly, capsiate suppressed VEGF-induced activation of Src kinase and phosphorylation of its downstream substrates, such as p125 FAK and VE-cadherin, without affecting autophosphorylation of the VEGF receptor KDR/Flk-1. In vitro kinase assay and molecular modeling studies revealed that capsiate inhibits Src kinase activity via its preferential docking to the ATP-binding site of Src kinase. Taken together, these results suggest that capsiate could be useful for blocking pathologic angiogenesis and vascular permeability caused by VEGF.
ISSN
0008-5472
Publisher
Amer Assoc Cancer Research
DOI
http://dx.doi.org/10.1158/0008-5472.CAN-07-2799
Type
Article
Appears in Collections:
Division of Biomedical Research > Biotherapeutics Translational Research Center > 1. Journal Articles
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