title: Effect of continuous vs intermittent application of 3-OH-tamoxifen or tamoxifen on the proliferation of the human breast cancer cell line MCF-7 M1.
abstract: The antiproliferative potency of 5 x 10(-7) M tamoxifen (TAM) and 3-hydroxytamoxifen (3-OH-TAM) was investigated during continuous (8 days) or intermittent (2 h every 2nd or 3rd day, respectively) application to the oestrogen-receptor-positive, estradiol-sensitive human mammary carcinoma cell line MCF-7 M1, a variant of MCF-7 wild type. Growth modulation was evaluated in parallel by counting cells and by measuring DNA content. Continuous incubation resulted in a growth inhibition to 21.8 +/- 3.2% by 3-OH-TAM and to 39.5 +/- 4.8% by TAM when compared with control cultures defined as 100%. Intermittent addition induced a growth reduction to 23.0 +/- 2.1% by 3-OH-TAM and to 41.2 +/- 2.4% by TAM in relation to 100% controls. Addition of 3-OH-TAM for 2 h only at day 1 resulted in an inhibition to 70.3 +/- 3.2%, again in relation to 100% controls. When TAM was administered once for 2 h at day 1 it induced an inhibition to 79.0 +/- 4.9% at day 8. The in vitro results indicate that (a) at 5 x 10(-7) M 3-OH-TAM has a better antiproliferative effectiveness than TAM, (b) the intermittent application is as effective as continuous application (no significant difference), and (c) the addition once a week reveals only a slight growth reduction after 8 days of culture. Application of the long-living TAM results in continuously high serum concentrations, which have been shown to create resistant cell clones. Compared to TAM the 3-OH metabolite has a considerably shorter half-life and its application in vivo reveals rise and fall of its serum concentrations. Since the presented data demonstrate that 3-OH-TAM is more potent than TAM and that the intermittent application is as effective as the continuous form, interval therapy with 3-OH-TAM may slow down the process of acquiring resistance to antioestrogens.
authors.affiliation: Institute of Pathology, University of Hamburg, Federal Republic of Germany.
authors.forename: M
authors.initials: M
authors.lastname: Dietel
authors.forename: R
authors.initials: R
authors.lastname: Löser
authors.forename: P
authors.initials: P
authors.lastname: Röhlke
authors.forename: W
authors.initials: W
authors.lastname: Jonat
authors.forename: A
authors.initials: A
authors.lastname: Niendorf
authors.forename: D
authors.initials: D
authors.lastname: Gerding
authors.forename: A
authors.initials: A
authors.lastname: Kohr
authors.forename: F
authors.initials: F
authors.lastname: Hölzel
authors.forename: H
authors.initials: H
authors.lastname: Arps
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D004965:Estrogen Antagonists; D013629:Tamoxifen; C038345:droloxifene