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

Bo Jeong Pyun, Sun Choi, Yoonji Lee, Tae Woong Kim, Jeong Ki Min, Yonghak Kim, Byung Dong Kim, Jeong Han Kim, Tae Yoon Kim, Young Myeong Kim, Young-Guen Kwon

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)227-235
Number of pages9
JournalCancer Research
Volume68
Issue number1
DOIs
Publication statusPublished - 2008 Jan 1

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src-Family Kinases
Capsaicin
Capillary Permeability
Vascular Endothelial Growth Factor A
Endothelial Cells
Pathologic Neovascularization
Capsicum
Vascular Endothelial Growth Factor Receptor
Intercellular Junctions
capsiate
Blood Vessels
Aorta
Permeability
Phosphotransferases
Adenosine Triphosphate
Binding Sites
Phosphorylation

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Pyun, Bo Jeong ; Choi, Sun ; Lee, Yoonji ; Kim, Tae Woong ; Min, Jeong Ki ; Kim, Yonghak ; Kim, Byung Dong ; Kim, Jeong Han ; Kim, Tae Yoon ; Kim, Young Myeong ; Kwon, Young-Guen. / Capsiate, a nonpungent capsaicin-like compound, inhibits angiogenesis and vascular permeability via a direct inhibition of Src kinase activity. In: Cancer Research. 2008 ; Vol. 68, No. 1. pp. 227-235.
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Capsiate, a nonpungent capsaicin-like compound, inhibits angiogenesis and vascular permeability via a direct inhibition of Src kinase activity. / Pyun, Bo Jeong; Choi, Sun; Lee, Yoonji; Kim, Tae Woong; Min, Jeong Ki; Kim, Yonghak; Kim, Byung Dong; Kim, Jeong Han; Kim, Tae Yoon; Kim, Young Myeong; Kwon, Young-Guen.

In: Cancer Research, Vol. 68, No. 1, 01.01.2008, p. 227-235.

Research output: Contribution to journalArticle

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AU - Kim, Young Myeong

AU - Kwon, Young-Guen

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