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

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.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Jeong SJ,Itokawa T,Shibuya M,Kuwano M,Ono M,Higuchi R,Miyamoto T

doi

10.1016/s0304-3835(02)00361-0

keywords:

subject

Has Abstract

pub_date

2002-12-10 00:00:00

pages

129-33

issue

1-2

eissn

0304-3835

issn

1872-7980

pii

S0304383502003610

journal_volume

187

pub_type

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