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Division of Environmental Sciences and Institute of Cancer Research, Columbia University, New York, New York 10032
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 µM), 12-O-tetradecanoylphorbol-13-acetate and phospholipid (50% inhibitory dose, 40 µM), 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 µM). Our findings suggest that the growth-inhibitory and cytotoxic effects of tamoxifen, which have been observed at µM concentrations of the drug, may be in part due to its effects on protein kinase C.
1 This work was supported by National Cancer Institute Grant CA-26056 and the Netherlands Cancer Foundation.
2 To whom requests for reprints should be addressed.
Received 10/29/84. Revised 1/22/85. Accepted 3/13/85.
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