© 2003 by European Society of Cardiology
Copyright © 2003, European Society of Cardiology
Involvement of cyclin-dependent pathway in the inhibitory effect of delphinidin on angiogenesis
Pharmacologie et Physico-Chimie des Interactions Cellulaires et Moléculaires, UMR CNRS 7034, Université Louis Pasteur de Strasbourg, 74 Route du Rhin, B.P. 24, 67401 Illkirch, France
* Corresponding author. Tel.: +33-390-244-264; fax: +33-390-244-313. claire{at}aspirine.u-strasbg.fr
Objective: Epidemiologic studies have shown that a diet rich in fruits and vegetables has a beneficial preventive effect for cancer and cardiovascular diseases. The mechanisms of these beneficial effects are not known although there is evidence that polyphenolic compounds in food may be of some benefit. The purpose of this study was to define the effect of delphinidin, a vasoactive polyphenol belonging to the class of anthocyanin, on endothelial cell proliferation and migration as well as on in vivo angiogenesis. Methods and results: Vascular endothelial growth factor-stimulated human umbilical endothelial cell migration and proliferation are potently inhibited by delphinidin. Flow cytometric analysis demonstrates that delphinidin inhibition of proliferation is correlated with the blockade of cell cycle in G0/G1 phase. Western blot analysis shows that delphinidin reverses the vascular endothelial growth factor-induced decrease in expression of cyclin-dependent kinase inhibitor p27kip1 and the vascular endothelial growth factor-induced increase of cyclin D1 and cyclin A, both being necessary to achieve the G1-to-S transition. Furthermore, delphinidin inhibits neovascularisation in vivo in chorioallantoic membrane model. Conclusion: Delphinidin overcomes in vitro and in vivo angiogenesis and thus appears promising for the development of an anti-angiogenic therapy.
KEYWORDS VEGF, vascular endothelial growth factor; bFGF, fibroblast growth factor; HUVEC, human umbilical vein endothelial cell; RWPC, red wine polyphenolic extract; cdk, cyclin dependent kinase; cki, cyclin kinase inhibitor of cyclin dependent kinase; DMSO, dimethylsulfoxide; HS, human serum; CAM, chorioallantoic membrane; L-NA, NG-L-nitroarginine; Delph, delphinidin
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