title: Characterization of the effects of the novel non-steroidal antiestrogen EM-800 on basal and estrogen-induced proliferation of T-47D, ZR-75-1 and MCF-7 human breast cancer cells in vitro.
abstract: Since estrogens play a predominant role in the development and growth of human breast cancer, antiestrogens represent a logical approach to the treatment of this disease. The present study compares the effects of the novel nonsteroidal anti-estrogen EM-800 and related compounds with those of a series of anti-estrogens on basal and 17 beta-estradiol (E2)-induced cell proliferation in human breast cancer cell lines. In the absence of added E2, EM-800 and related compounds failed to change basal cell proliferation, thus showing the absence of intrinsic estrogenic activity in the ER-positive T-47D, ZR-75-1 and MCF-7 cell lines. The stimulation of T-47D cell proliferation induced by 0.1 nM E2 was competitively blocked by a simultaneous incubation with EM-652, EM-800, OH-tamoxifen, OH-toremifene, ICI 182780, ICI 164384, droloxifene, tamoxifen and toremifene at apparent Ki values of 0.015, 0.011-0.017, 0.040-0.054, 0.043, 0.044, 0.243 and 0.735 nM, approx. 10 nM and > 10 nM, respectively. Similar data were obtained in ZR-75-1 and/or MCF-7 cells. Moreover, EM-652 was 6-fold more potent than OH-Tamoxifen in inhibiting the proportion of cycling MCF-7 cells. Our data show that EM-800 and EM-652 are the most potent known antiestrogens in human breast cancer cells in vitro and that they are devoid of the estrogenic activity of OH-tamoxifen and droloxifene suggested by stimulation of cell growth in the absence of estrogens in ZR-75-1 and MCF-7 cells.
authors.affiliation: Laboratory of Molecular Endocrinology, CHUL Research Center, Québec, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Simard
authors.forename: C
authors.initials: C
authors.lastname: Labrie
authors.forename: A
authors.initials: A
authors.lastname: Bélanger
authors.forename: S
authors.initials: S
authors.lastname: Gauthier
authors.forename: S M
authors.initials: SM
authors.lastname: Singh
authors.forename: Y
authors.initials: Y
authors.lastname: Mérand
authors.forename: F
authors.initials: F
authors.lastname: Labrie
mesh_terms: D001578:Benzopyrans / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D006801:Humans; D011422:Propionates / Q000494:pharmacology*; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D001578:Benzopyrans; D004965:Estrogen Antagonists; D011422:Propionates; D013629:Tamoxifen; C038345:droloxifene; C016601:afimoxifene; D004958:Estradiol; C106945:EM 800