title: Alteration in proliferative and endocrine responsiveness of human mammary carcinoma cells by prototypic tumor-suppressing agents.
abstract: The experiments performed in this study were designed to establish that (1) acquisition of anchorage-independent growth, a biological characteristic of tumorigenically transformed phenotype, can be modulated by prototypic tumor-suppressing agents, and (2) modulation of growth is influenced by the metabolic competence of the cells to biotransform estradiol, MCF-7 human breast carcinoma cells exhibited linear cell proliferative kinetics with a 41-hour population doubling time, and a 15% colony-forming efficiency in 0.33% agar. Indole-3-carbinol (13C), a naturally occurring tumor-suppressive agent; tamoxifen (TAM), an antiestrogenic agent; and 4-hydroxytamoxifen (4-OHTAM), a metabolite of TAM, demonstrated 73.7%, 72.5%, and 89.9% suppression in anchorage-independent growth of MCF-7 cells, respectively. At the metabolic level, 13C and 4-OHTAM induced 2.3-fold (P < 0.0001) and 1.3-fold increase (P = 0.001) relative to their own controls in the extent of 2-hydroxylation of estradiol. The results indicate that growth inhibition by 13C, TAM, and 4-OHTAM may in part be due to altered estradiol metabolism in MCF-7 cells. Thus, anchorage-independent growth and altered biotransformation of estradiol may constitute useful cellular and endocrine markers to evaluate the biological response of chemosuppressive agents.
authors.affiliation: Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Suto
authors.forename: H L
authors.initials: HL
authors.lastname: Bradlow
authors.forename: T
authors.initials: T
authors.lastname: Kubota
authors.forename: M
authors.initials: M
authors.lastname: Kitajima
authors.forename: G Y
authors.initials: GY
authors.lastname: Wong
authors.forename: M P
authors.initials: MP
authors.lastname: Osborne
authors.forename: N T
authors.initials: NT
authors.lastname: Telang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D004958:Estradiol / Q000378:metabolism*; D006801:Humans; D006900:Hydroxylation; D007211:Indoles / Q000494:pharmacology; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D013629:Tamoxifen; C016601:afimoxifene; D004958:Estradiol; C016517:indole-3-carbinol