Reduction of the membrane fluidity of human breast cancer cells by tamoxifen and 17 beta-estradiol.
The intracellular steady-state levels of methotrexate were previously shown to be reduced in estrogen receptor (ER)-negative human breast cancer MDA-MB-436 cells and ER-positive human breast cancer MCF7 cells following treatment with pharmacologically relevant concentrations of 17 beta-estradiol (E2). We now report that both E2 and tamoxifen (TMX) significantly decreased the fluidity of MCF7 and MDA-MB-436 cellular membranes. With E2 or TMX at concentrations greater than 1 microM, perturbations in membrane fluidity were accompanied by apparently non-ER-mediated cytotoxicity. Alterations in membrane structure may have contributed to the cytotoxicity of high-dose endocrine therapy and to the ability of E2 to inhibit methotrexate transport and cytotoxicity in some human breast cancer cells.
Clarke
R
R
Vincent T. Lombardi Cancer Research Center, Georgetown University Medical School, Washington, DC 20007.
van den Berg
H W
HW
Murphy
R F
RF
D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000648:ultrastructure*; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008560:Membrane Fluidity / Q000187:drug effects*; D013629:Tamoxifen / Q000008:administration & dosage / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D013629:Tamoxifen; D004958:Estradiol; D004247:DNA