Inhibition of protein kinase C by tamoxifen.
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 microM), 12-O-tetradecanoylphorbol-13-acetate and phospholipid (50% inhibitory dose, 40 microM), or teleocidin 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 is inhibited by tamoxifen (50% inhibitory dose, 5 microM). Our findings suggest that the growth-inhibitory and cytotoxic effects of tamoxifen, which have been observed at microM concentrations of the drug, may be in part due to its effects on protein kinase C.
Mesh Terms:
Animals, Brain, Phorbol 12,13-Dibutyrate, Phorbol Esters, Phospholipids, Protein Kinase C, Protein Kinase Inhibitors, Rats, Tamoxifen, Tetradecanoylphorbol Acetate
Animals, Brain, Phorbol 12,13-Dibutyrate, Phorbol Esters, Phospholipids, Protein Kinase C, Protein Kinase Inhibitors, Rats, Tamoxifen, Tetradecanoylphorbol Acetate
Cancer Res.
Date: Jun. 01, 1985
PubMed ID: 3157445
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