Delphinidin inhibits endothelial cell proliferation and cell cycle progression through a transient activation of ERK-1/-2.
Epidemiological studies have shown that a diet rich in fruits and vegetables might reduce the risk of cardiovascular diseases and protect against cancer by mechanisms that have not been elucidated yet. This study was aimed to define the effect of delphinidin, a vasoactive polyphenol belonging to the class of anthocyanin, on bovine aortic endothelial cells (BAECs) proliferation. Delphinidin inhibited serum- and vascular endothelium growth factor-induced BAECs proliferation. This antiproliferative effect of delphinidin, is triggered by ERK-1/-2 activation, independent of nitric oxide pathway and is correlated with suppression of cell progression by blocking the cell cycle in G(0)/G(1) phase. Furthermore, suppression of cell cycle progression is associated with the modulation of the mitogenic signaling transduction cascade. This includes over-expression of caveolin-1 and p21(WAF1/Cip1) and down-expression of Ras and cyclin D1. In conclusion, the antiproliferative effect of delphinidin may be of importance in preventing both plaque development and stability in atherosclerosis and tumor dissemination in cancer.
Martin
Sophie
S
Pharmacologie et Physico-Chimie des Interactions Cellulaires et Moléculaires, UMR CNRS 7034, Faculté de Pharmacie, Université Louis Pasteur, 74 route du Rhin, BP 24, 67401 Illkirch, France.
Favot
Laure
L
Matz
Rachel
R
Lugnier
Claire
C
Andriantsitohaina
Ramaroson
R
D000818:Animals; D000872:Anthocyanins / Q000494:pharmacology*; D002417:Cattle; D051242:Caveolin 1; D022461:Caveolins / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D016228:Endothelial Growth Factors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D016193:G1 Phase / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007106:Immune Sera / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D008222:Lymphokines / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D016196:S Phase / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D018631:ras Proteins / Q000378:metabolism
D000872:Anthocyanins; D051242:Caveolin 1; D022461:Caveolins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016228:Endothelial Growth Factors; D007106:Immune Sera; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D019938:Cyclin D1; D009569:Nitric Oxide; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins; C017185:delphinidin