title: Carrier mediated action of platinum complexes on estrogen receptor positive tumors.
abstract: Three 1,2-diaminoethane-dichloro-platinum(II) complexes linked to 5-hydroxy-2-(4-hydroxyphenyl)-3-methylindole by spacer groups of varying length were evaluated for cytostatic activity in estrogen receptor (ER) positive and negative tumor cells. In vitro, only the growth of ER positive MCF-7 mammary tumor cells was inhibited whereas hormone independent MDA-MB 231 cells did not respond. In vivo, a strong inhibitory effect was only observed in ER positive MXT mammary tumors of the mouse. The complex with a hexyl group as spacer reduced the tumor weight by 89% after 6 weeks of treatment. The R 3327 Dunning prostatic tumor of the rat, which also contains ER was inhibited, too. Generally, the effect in ER negative tumors was weak. These findings can be rationalized by the high binding affinities of the complexes for ER. By the mouse uterine weight test it was shown that the endocrine activity of the complexes is very low. Therefore, a mode of action different from that exerted by estrogens or antiestrogens has to be assumed.
authors.affiliation: Institut für Pharmazie, Universität Regensburg, Regensburg, F.R.G.
authors.forename: N
authors.initials: N
authors.lastname: Knebel
authors.forename: C D
authors.initials: CD
authors.lastname: Schiller
authors.forename: M R
authors.initials: MR
authors.lastname: Schneider
authors.forename: H
authors.initials: H
authors.lastname: Schönenberger
authors.forename: E
authors.initials: E
authors.lastname: von Angerer
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy; D004337:Drug Carriers; D005260:Female; D006801:Humans; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000032:analysis / Q000188:drug therapy*; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size / Q000187:drug effects; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy; D011960:Receptors, Estrogen / Q000032:analysis*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014599:Uterus / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D009944:Organoplatinum Compounds; D011960:Receptors, Estrogen; C002892:platinum ethylenediamine dichloride