[Meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl)enthylenediamine] dichloroplatinum(II), an estrogenic platinum(II)-complex for the therapy of breast cancer: relationship between stability and effect

Abstract

The inhibiting effect of [meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]dichloroplatinum(II) (meso-Pt(1)Cl2) (I) on the estrogen receptor-pos. (ER+) breast cancer in vivo is due to its cytotoxic as well as its estrogenic properties. In in vitro expts. on the ER+ MCF-7 breast cancer cell line meso-Pt(1)Cl2 can react with bionucleophils in cell culture medium, esp. with serum proteins, which leads to the release of the pharmacol. active diammine ligand. The comparison of the kinetics of ligand release with the exposure time required for meso-Pt(1)Cl2 to induce its cytotoxic and estrogenic effects (i.e. induction of ER-processing and progesterone receptor synthesis) show that the biol. response of the MCF-7 cells can be attributed to the intact meso-Pt(1)Cl2.