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.