Costunolide, a sesquiterpene lactone from Saussurea lappa, inhibits the VEGFR KDR/Flk-1 signaling pathway

Sei Joon Jeong, Takashi Itokawa, Masabumi Shibuya, Michihiko Kuwano, Mayumi Ono, Ryuichi Higuchi, Tomofumi Miyamoto

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Costunolide (CT), a sesquiterpene lactone constituent isolated from Saussurea lappa (Compositae), exerted an antiangiogenic effect. CT selectively inhibited the endothelial cell proliferation induced by vascular endothelial growth factor (VEGF). Further, CT was also found to inhibit the VEGF-induced chemotaxis of human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner. From these results, we hypothesized that CT might inhibit angiogenesis by blocking the angiogenic factor signaling pathway. VEGF interacts with its cognate receptors, KDR/Flk-1 and Flt-1, and exerts its angiogenic effect. CT inhibited the autophosphorylation of KDR/Flk-1 without affecting that of Flt-1. Moreover, administration of CT reduced VEGF-induced neovascularization in a mouse corneal micropocket assay. These results suggest that CT may prove useful for the development of a novel angiogenesis inhibitor.

Original languageEnglish
Pages (from-to)129-133
Number of pages5
JournalCancer Letters
Volume187
Issue number1-2
DOIs
Publication statusPublished - Dec 10 2002

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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