Tumor-promoting phorbol esters stimulate bovine cerebral cortex capillary endothelial cell growth in vitro

The active tumor promoters, 12-O-tetradecanoyl phorbol 13-acetate (TPA) and phorbol 12, 13-dibutyrate (PDBu), which activate protein kinase C (PKC), were found to stimulate bovine brain cortex capillary endothelial cell (CEC) proliferation in a dose-dependent manner. 4 alpha-phorbol-12, 13-didecanoate (4 alpha-PDD), known to be inactive for PKC, was without effect in stimulating CEC proliferation. Furthermore, prolonged incubation with TPA led to a decrease in the number of [3H]-PDBu binding sites with a parallel loss of responses of the cells to TPA. Finally, staurosporine, a potent PKC inhibitor, showed a strong antiproliferative effect on CEC (IC50 = 1.3 nM). Therefore, this work suggests that PKC plays a fundamental role in CEC growth.