In the search for new anti-
breast cancer compounds a series of diastereomeric aqua[1-(2,6-dichloro-4-hydroxyphenyl)-2-phenylethylenediamine]sulfato
platinum(II) complexes was tested on the
hormone-sensitive MXT-M-3.2
breast cancer of the mouse. By simultaneous determination of
tumor and uterine weights at the end of the experiment we obtained an insight into the mode of action. Changes in the uterine weights indicate whether the anti-
breast cancer effect of the test substance is caused either by its capability to reduce the endogenous
estrogen level via inhibition of
estrogen biosynthesis (mechanism B), or by its estrogenic side effects which enhance the immune defense in the host animals (mechanism C). Studies on the [3H]
thymidine incorporation into
DNA of MDAMB-231
breast cancer cells showed that all test compounds inhibit
deoxyribonucleic acid synthesis, like
cisplatin (mechanism A). However, in comparison to the standard
cisplatin, their activities were low. The three most effective test compounds threo-2-PtSO4 (2-phenyl-residue), threo-5-PtSO4 (2-(4-hydroxyphenyl)-residue), and threo-8-PtSO4 (2-(2-fluoro-4-hydroxyphenyl)-residue) seem to exert their anti-
breast cancer effect by mechanism B. Moreover, threo-5-PtSO4 was moderately active on the
hormone- insensitive MXT-M-3.2 (
Ovex)
breast cancer of the mouse. Aqua[erythro-1-(2,6-dichloro-4-hydroxyphenyl)-2-(2-chloro-4-hydroxypheny l)
ethylenediamine]sulfato-
platinum(II) (erythro-9-PtSO4) was the only
breast cancer inhibiting compound of the series acting mainly according to mechanism C. A minor contribution of mechanism A, impairment of the
DNA function in the
tumor cell, to the anti-
breast cancer activity of these aqua[1-(2,6-dichloro-4-hydroxyphenyl)-2-phenylethylenediamine]sulfato
platinum(II) complexes cannot be excluded, since such effects are apparent in the MDA-MB-231 as well as in the MCF-7
breast cancer cell line at higher drug concentrations. In this test series which was performed with the
crystal violet chemosensitivity assay, the MCF-7 cells proved to be somewhat more sensitive.