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.
Daviet
I
I
Sanofi Recherche, Toulouse, France.
Herbert
J M
JM
Maffrand
J P
JP
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000098:blood supply; D004730:Endothelium, Vascular / Q000166:cytology*; D066298:In Vitro Techniques; D010703:Phorbol Esters / Q000494:pharmacology*; D011493:Protein Kinase C / Q000502:physiology*; D019311:Staurosporine
D000470:Alkaloids; D002273:Carcinogens; D010703:Phorbol Esters; D011493:Protein Kinase C; D019311:Staurosporine