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Tamoxifen inhibits uptake and metabolism of ethanolamine and choline in multidrug‐resistant, but not in drug‐sensitive, MCF‐7 human breast carcinoma cells
Author(s) -
Kiss Zoltan,
Crilly Karan S
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)00094-p
Subject(s) - mcf 7 , tamoxifen , p glycoprotein , efflux , pharmacology , estrogen receptor , choline , ethanolamine , multiple drug resistance , antiestrogen , phosphocholine , phosphatidylethanolamine , cancer cell , chemistry , fulvestrant , cancer research , medicine , breast cancer , biology , biochemistry , cancer , phospholipid , phosphatidylcholine , human breast , membrane , antibiotics
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 μM) 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 of phosphatidylethanolamine (PtdEtn), inhibition of PtdEtn synthesis may represent an additional mechanism by which TAM inhibits P‐gp‐mediated drug efflux.