Biological activities of malvidin, a red wine anthocyanidin.
Malvidin (mv) has been identified as a potential inhibitor of 3',5'-cyclic adenosine monophosphate (cAMP) phosphodiesterases (PDE). This study was to investigate if, as a possible consequence of intracellular PDE inhibition, the activity of the mitogen-activated protein kinase (MAPK) cascade is affected by mv treatment. At a concentration of 5 microM of mv a significant decrease of phosphorylated ERK1 and ERK2 (ERK, extracellular regulated kinase) in HT29 cells was observed. However, an increase in substance concentration led to a substantial recurrence of the phosphorylated enzymes. Cell cycle analysis underlined that indeed G(1)-relevant targets are only marginally affected by mv. The recurrence of phosphorylated ERK1/2 and the lack of effectiveness on the G(1)-passage up to 100 microM indicated that the inhibition of cAMP-specific PDEs is of minor relevance for the growth-inhibitory properties of mv in HT29 cells. In contrast, the release of cells, synchronised in the G(2)/M-phase of the cell cycle by nocodazole treatment, was effectively blocked in the presence of 1 microM mv. These results suggest that mv interferes with cellular targets relevant for G(2)/M-progression which have not been identified so far.
Fritz
Jessica
J
Section of Food Toxicology, Institute of Applied Biosciences, University of Karlsruhe TH, Germany.
Kern
Melanie
M
Pahlke
Gudrun
G
Vatter
Sandra
S
Marko
Doris
D
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000872:Anthocyanins / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016195:G2 Phase / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000032:analysis; D048052:Mitogen-Activated Protein Kinase 3 / Q000032:analysis; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D015739:Nocodazole / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010766:Phosphorylation; D014920:Wine / Q000032:analysis*
D000872:Anthocyanins; D004791:Enzyme Inhibitors; D010726:Phosphodiesterase Inhibitors; C065861:malvidin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D015739:Nocodazole