title: In vitro evaluation of 1-(2-chloroethyl)-1-nitroso-3-(2-hydroxyethyl)urea linked to 4-acetoxy-bisdesmethyltamoxifen, estradiol and dihydrotestosterone.
abstract: The anticancer efficacies of three 1-(2-chloroethyl)-1-nitroso-3-(2- hydroxyethyl)urea (HECNU) derivatives--4-acetoxybisdesmethyltamoxifen-1,4-hemisuccinate-H ECNU (4-OAc-BDMT-hs-HECNU), 17-beta-estradiol-1,4-hemisuccinate-HECNU (E2-hs-HECNU) and 17-dihydrotestosterone-1,4-hemisuccinate-HECNU (DHT-hs-HECNU)--are compared with their unlinked equimolar mixtures using the estrogen and androgen receptor positive cell line MCF-7. Following 72 h incubation at a concentration of 100 mumol/l, 4-OAc-BDMT-hs-HECNU and DHT-hs-HECNU have a growth inhibitory effect of 76% and 73%, respectively, whereas E2-hs-HECNU causes an inhibition of 55%. Within this time period, DHT-hs-HECNU (100 mumol/l) is more effective as compared to the unlinked equimolar combination of HECNU plus dihydrotestosterone; E2-hs-HECNU (100 mumol/l) is slightly more and 4-OAc-BDMT-hs-HECNU (100 mumol/l) is even less effective than the respective unlinked equimolar mixtures. At this concentration (100 mumol/l) the growth inhibitory effect of 4-OAc-BDMT-hs-HECNU is not antagonized by coincubation with estradiol.
authors.affiliation: Deutsches Krebsforschungszentrum, Institut für Toxikologie und Chemotherapie, Heidelberg, Fed. Rep. of Germany.
authors.forename: F
authors.initials: F
authors.lastname: Kaleagasioglu
authors.forename: M R
authors.initials: MR
authors.lastname: Berger
authors.forename: D
authors.initials: D
authors.lastname: Schmähl
authors.forename: G
authors.initials: G
authors.lastname: Eisenbrand
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D009607:Nitrosourea Compounds / Q000494:pharmacology*; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D013196:Dihydrotestosterone; D013629:Tamoxifen; D004958:Estradiol; C013876:elmustine