Tamoxifen inhibits uptake and metabolism of ethanolamine and choline in multidrug-resistant, but not in drug-sensitive, MCF-7 human breast carcinoma cells.

Tamoxifen (TAM), a widely used agent in the hormonal therapy of breast cancer, is also an antagonist of P-glycoprotein (P-gp), a cell surface protein which confers drug resistance to cells. Here we report that in an estrogen receptor-deficient multidrug-resistant subline of MCF-7 human breast carcinoma cells (MCF-7/MDR), but not in the parent drug-sensitive cells (MCF-7/WT), clinically relevant concentrations (1-5 microM) of TAM inhibited the uptake and phosphorylation of ethanolamine and choline. These inhibitory effects resulted in decreased synthesis of the corresponding phospholipids. In view of the known dependence of P-gp function on phosphatidylethanolamine (PtdEtn), inhibition of PtdEtn synthesis may represent an additional mechanism by which TAM inhibits P-gp-mediated drug efflux.