[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

✍ Scribed by Sabine Schertl; Rolf W. Hartmann; Christine Batzl-Hartmann; Günther Bernhardt; Thilo Spruß; Karin Beckenlehner; Marion Koch; Rudolf Krauser; Richard Schlemmer; Ronald Gust; Helmut Schönenberger

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 155 KB
• Volume: 337
• Category: Article
• ISSN: 0365-6233
• DOI: 10.1002/ardp.200300855

✦ Synopsis

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.