Involvement of cyclin-dependent pathway in the inhibitory effect of delphinidin on angiogenesis.
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.


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 G(0)/G(1) phase. Western blot analysis shows that delphinidin reverses the vascular endothelial growth factor-induced decrease in expression of cyclin-dependent kinase inhibitor p27(kip1) and the vascular endothelial growth factor-induced increase of cyclin D1 and cyclin A, both being necessary to achieve the G(1)-to-S transition. Furthermore, delphinidin inhibits neovascularisation in vivo in chorioallantoic membrane model.


CONCLUSIONS
Delphinidin overcomes in vitro and in vivo angiogenesis and thus appears promising for the development of an anti-angiogenic therapy.
Favot
Laure
L
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.
Martin
Sophie
S
Keravis
Thérèse
T
Andriantsitohaina
Ramaroson
R
Lugnier
Claire
C
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000872:Anthocyanins / Q000494:pharmacology*; D015153:Blotting, Western / Q000379:methods; D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D016213:Cyclins / Q000378:metabolism*; D003864:Depression, Chemical; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D020533:Angiogenesis Inhibitors; D000872:Anthocyanins; D016213:Cyclins; D042461:Vascular Endothelial Growth Factor A; C017185:delphinidin