Protein kinase C inhibitor (H-7) potentiates antiproliferative effects of a polyamine biosynthesis inhibitor.

In this study, a protein kinase C inhibitor, H-7, was found to potentiate the antiproliferative effects of difluoromethyl ornithine (DFMO), inhibitor of the polyamine biosynthesis, on NIH 3T3 and 3T3/SV40 cells in culture. Incubation of the cells with DFMO inhibited the cell growth, whereas the addition of polyamine spermidine to these cells restored the normal rate of cell proliferation with the fact that these cells took up the polyamine from the extracellular medium to compensate the intracellular needs. The addition of H-7 to both the 3T3 and 3T3/SV40 cells, inhibited the cell proliferation, though the level of inhibition was always lower than in those treated with the DFMO alone. The addition of H-7 to the DFMO containing cells potentiated the antiproliferative effects of the latter with the fact that the former inhibited the uptake of the spermidine, though there might be additional targets, like the protein kinase C, involved in the inhibition process.