DNA-binding activity and cytotoxicity of Pt-berenil compounds in MDA-MB-231 and MCF-7 breast cancer cells.

The compounds of formula [Pt2Cl4(berenil)2]Cl4 and [Pt2Cl2(NH3)2(berenil)2]Cl4 were examined for cytotoxicity in breast cancer cell cultures and for inhibition of topoisomerases I and II. Evaluation of the cytotoxicity of these compounds employing a MTT assay and inhibition of [3H]thymidine incorporation into DNA in both MDA-MB-231 and MCF-7 breast cancer cells demonstrated that these compounds were more active than cisplatin. The DNA-binding ability of these compounds was evaluated by an ultrafiltration method using calf thymus DNA, poly(dA-dT)2 and poly(dG-dC)2, indicated that these compounds show strong specificity for AT base pairs. Binding studies indicate that these compounds bind more tightly to double-stranded DNA than cisplatin. The degree to which these compounds inhibited cell growth breast cancer cells was generally consistent with their relative DNA binding affinity. Mechanistic studies revealed that these compounds act as topoisomerase II (topo II) inhibitors in plasmid relaxation assays.