title: [1, 2-Bis(2, 6-difluoro-3-hydroxyphenyl)ethylene-diamine]platinum(II) complexes, compounds for the endocrine therapy of breast cancer - mode of action I: antitumor activity due to the reduction of the endogenous estrogen level.
abstract: Aqua[meso-1, 2-bis(2, 6-difluoro-3-hydroxyphenyl)ethylenediamine]sulfatoplatinum(II) (meso-3-PtSO(4)) and its racemate (rac-3-PtSO(4)) are highly active on the hormone-sensitive MXT-M-3, 2 breast cancer of the mouse. In vitro, on the MXT(+) cell culture derived from this tumor, however, they are inactive (meso-3-PtSO(4)) or moderately active (rac-3-PtSO(4)) in concentrations corresponding to levels of these drugs in animal experiments. The in vivo effect is mainly caused by a reduction of the endogenous estrogen level in the host animals due to an interference with the ovarian steroid biosynthesis as demonstrated for meso-3-PtSO(4). Therefore, a reversal of the breast cancer inhibiting effect of meso-3-PtSO(4) can be achieved by simultaneous estrone administration. Histological results on ovaries, uterus, and tumor of meso-3-PtSO(4)-treated mice also favor such a mode of action. However, especially for rac-3-PtSO(4) cytotoxic effects contributing to the anti-breast cancer activity cannot be excluded. Considerations on the mode of action of Pt-complexes which inhibit breast cancer by interference with estrogen receptor mediated processes of growth control and with DNA replication are presented.
authors.affiliation: Lehrstuhl für Pharmazeutische Chemie II, Institut für Pharmazie, Universität Regensburg, Regensburg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Schertl
authors.forename: Rolf W
authors.initials: RW
authors.lastname: Hartmann
authors.forename: Christine
authors.initials: C
authors.lastname: Batzl-Hartmann
authors.forename: Günther
authors.initials: G
authors.lastname: Bernhardt
authors.forename: Thilo
authors.initials: T
authors.lastname: Spruss
authors.forename: Karin
authors.initials: K
authors.lastname: Beckenlehner
authors.forename: Marion
authors.initials: M
authors.lastname: Koch
authors.forename: Rudolf
authors.initials: R
authors.lastname: Krauser
authors.forename: Richard
authors.initials: R
authors.lastname: Schlemmer
authors.forename: Ronald
authors.initials: R
authors.lastname: Gust
authors.forename: Helmut
authors.initials: H
authors.lastname: Schönenberger
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004967:Estrogens / Q000096:biosynthesis / Q000378:metabolism*; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D010053:Ovary / Q000187:drug effects / Q000473:pathology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013997:Time Factors; D014599:Uterus / Q000187:drug effects / Q000473:pathology
chemical_list: C488612:(1,2-bis(2, 6-difluoro-3-hydroxyphenyl)ethylene-diamine)platinum(II); D018931:Antineoplastic Agents, Hormonal; D004967:Estrogens; D009944:Organoplatinum Compounds