INHIBITION OF PROTEIN KINASE-C BY TAMOXIFEN

Abstract

The antiestrogen drug tamoxifen inhibits rat brain protein kinase C in vitro, whether the enzyme is activated by Ca2+ and phospholipid (50% inhibitory dose, 100 .mu.M), 12-O-tetradecanoyl-phorbol-13-acetate and phospholipid (50% inhibitory dose, 40 .mu.M), or telecoidin and phospholipid. Tamoxifen does not inhibit the Ca2+- and phospholipid-independent phosphorylation of protamine sulfate by protein kinase C, indicating that the drug does not interact with the active site of the enzyme. The binding of [3H]phorbol dibutyrate to high-affinity membrane receptors of cultured mouse fibroblast cells was inhibited by tamoxifen (50% inhibitory dose, 5 .mu.M). The growth-inhibitory and cytotoxic effects of tamoxifen, which were observed at .mu.M concentrations of the drug, may be in part due to its effects on protein kinase C. [The use of this drug to treat breast cancer was described.].