Heterobimetallic platinum(ii) complexes with increased cytotoxicity against ovarian cancer cell lines

Abstract

Two series of heterobimetallic compounds were prepared from the starting complex [cis-L₂PtCl₂] containing an aminophosphine ligand (L = 2,6-iPr₂-C₆H₃-NHPPh₂). They include neutral Pt–Sn complexes [cis-L₂PtX(SnCl₃)] (X = Cl, SnCl₃) and ionic Pt–Ag complexes [cis-L₂PtCl₂Ag]X (X = OTf, PF₆). The in vitro WST-1 assays of the ionic complexes revealed a high cytotoxic effect on ovarian cancer cells, including the cisplatin resistant cell line A2780cis, while the sensitivity to the non-cancer cell line MRC-5 stays very low. The mechanism of the cytotoxic effect was studied in detail on one representative. It revealed the up-regulation of the apoptotic proteins p38 and BAX, activation of caspase 9 and initiation of cell apoptosis. Here, cell death is accompanied by an increased amount of p21 protein and increased activity of the check point kinases, which result in the G2 arrest. Sensitivity to cisplatin resistant cells, high selectivity to cancer cells and activity at a low dosage are the advantages of the Pt–Ag compounds presented here.