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

FEBS Letters

Crilly, Karan S¹  Kiss, Zoltan¹ 

[1] The Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912, USA

关键词: Tamoxifen;    Phosphatidylethanolamine synthesis;    P-glycoprotein;    Breast cancer;    TAM;    tamoxifen;    Etn;    ethanolamine;    EtnP;    ethanolamine phosphate;    Cho;    choline;    ChoP;    choline phosphate;    PtdEtn;    phosphatidylethanolamine;    PtdCho;    phosphatidylcholine;    P-gp;    P-glycoprotein;   

DOI  :  10.1016/0014-5793(95)00094-P

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown