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[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
Author(s) -
Schertl Sabine,
Hartmann Rolf W.,
BatzlHartmann Christine,
Bernhardt Günther,
Spruß Thilo,
Beckenlehner Karin,
Koch Marion,
Krauser Rudolf,
Schlemmer Richard,
Gust Ronald,
Schönenberger Helmut
Publication year - 2004
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200300855
Subject(s) - chemistry , mode of action , estrone , breast cancer , in vivo , estrogen , estrogen receptor , ovarian cancer , endocrinology , ethylenediamine , cancer , cancer research , in vitro , medicine , pharmacology , hormone , biology , biochemistry , microbiology and biotechnology , inorganic chemistry
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.