Inhibition of DNA synthesis by phorbol esters through protein kinase C in cultured rabbit aortic smooth muscle cells

Abstract

In cultured rabbit aortic smooth muscle cells (SMC), 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) induced DNA synthesis in the presence of plasma‐derived serum to a small extent, but inhibited markedly the rabbit whole blood serum (WBS)‐, platelet‐derived growth factor (PDGF)‐ and epidermal growth factor‐induced DNA synthesis. Phorbol‐12,13‐dibutyrate (PDBu) mimicked this antiproliferative action of TPA, but 4α‐phorbol‐12, 13‐didecanoate was inactive in this capacity. Prolonged treatment of the cells with PDBu caused the partial down‐regulation of protein kinase C. In these protein kinase C‐reduced cells, WBS still induced DNA synthesis, but TPA did not inhibit the WBS‐induced DNA synthesis. We have previously shown that protein kinase C is involved at least partially in the PDGF‐induced DNA synthesis in rabbit aortic SMC. The present results together with this earlier observation suggest that protein kinase C has not only a proliferative but also an antiproliferative action in rabbit aortic SMC.