title: Activity of tamoxifen and new antiestrogens on estrogen receptor positive and negative breast cancer cells.
abstract: The effect of some new antiestrogens (ICI 164384, ICI 182780, Ly 133314 and Ly 117018) on the growth of a panel of breast cancer cell lines (MDA-MB 231, BT20, MCF7 and T47D) was studied. Their antiestrogenic activity was investigated in the presence of a physiologic concentration of estradiol and compared with the effect displayed by tamoxifen in the same experimental conditions. Tamoxifen confirmed its antagonistic activity in the presence of estradiol, whereas when given alone it did not exhibit a clear antiproliferative effect. All other compounds showed variable activity: ICI 164384 and ICI 182780 exerted a variable inhibitory effect in all cell lines, but only in the absence of estradiol; Ly 133314 and Ly 117018 did not show a clear antagonistic activity and sometimes had a synergistic effect with estradiol in increasing cell growth. These results indicate an extreme variability in terms of antagonistic effect of these new compounds and suggest their inadequacy to replace tamoxifen as an antiestrogen during endocrine treatment. Interestingly, ICI 164384 exerted an antiproliferative action also an estrogen receptor-negative cell lines, probably through an alternative mechanism non estrogen receptor-mediated, supporting the hypothesis that it could be effective on estrogen receptor-positive as well as estrogen receptor-negative tumors.
authors.affiliation: Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Coradini
authors.forename: A
authors.initials: A
authors.lastname: Biffi
authors.forename: V
authors.initials: V
authors.lastname: Cappelletti
authors.forename: G
authors.initials: G
authors.lastname: Di Fronzo
mesh_terms: D001943:Breast Neoplasms / Q000737:chemistry / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D053284:Polyunsaturated Alkamides; D011759:Pyrrolidines / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000032:analysis*; D013629:Tamoxifen / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D004965:Estrogen Antagonists; D053284:Polyunsaturated Alkamides; D011759:Pyrrolidines; D011960:Receptors, Estrogen; D013876:Thiophenes; D013629:Tamoxifen; D000077267:Fulvestrant; D004958:Estradiol; C025430:LY 117018; C051781:ICI 164384; C014934:trioxifene