CAPE suppresses VEGFR-2 activation, and tumor neovascularization and growth

Tae Wook Chung, Seok Jo Kim, Hee Jung Choi, Choong Hwan Kwak, Kwon Ho Song, Seok Jong Suh, Keuk Jun Kim, Ki Tae Ha, Young Guk Park, Young Chae Chang, Hyeun Wook Chang, Young Choon Lee, Cheorl Ho Kim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

The growth and metastasis of human solid tumors and the development of conditions such as diabetic retinopathy, rheumatoid arthritis, inflammatory psoriasis, and others are regulated by the balance between angiogenic stimulators and inhibitors released in the angiogenic-pathological microenvironment. Vascular endothelial growth factor (VEGF), an angiogenic factor, is a potent endothelial-specific mitogen that activates endothelial cells in pathological angiogenesis. Recently, we demonstrated that caffeic acid phenethyl ester (CAPE) inhibits tumor growth, invasion, and metastasis. However, the precise molecular mechanism underlying the inhibitory effect of CAPE on VEGF-mediated angiogenesis remains unknown. Here, we show that CAPE suppressed VEGF-induced proliferation, tube formation, migration, the formation of actin stress fibers and loss of VE-cadherin at cell-cell contacts in endothelial cells, indicating the inhibition of VEGF-mediated VEGF receptor-2 (VEGFR-2) and its downstream signal activation in vitro. CAPE blocked VEGF-stimulated neovascularization in the Matrigel plugs assay, and reduced vascular permeability in mouse skin capillaries in vivo. CAPE inhibited the growth and neovascularization of primary tumor cells in C57BL/6 and BALB/c mice inoculated with Lewis lung carcinoma, colon carcinoma, and melanoma cells. These results suggest that CAPE negatively modulates VEGF-induced angiogenesis by suppressing VEGFR-2 activation, and might be a therapeutic avenue for anti-angiogenesis.

Original languageEnglish (US)
Pages (from-to)271-282
Number of pages12
JournalJournal of Molecular Medicine
Volume91
Issue number2
DOIs
StatePublished - Feb 2013

Keywords

  • Angiogenesis
  • Caffeic acid phenethyl ester (CAPE)
  • Vascular endothelial growth factor (VEGF)
  • Vascular endothelial growth factor receptor-2 (VEGFR-2)

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)

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