Heterobimetallic Platinum(II) Complexes with Increased Cytotoxicity against Ovarian Cancer Cell Lines

Two series of heterobimetallic compounds were prepared from the starting complex [cis-L2PtCl2] containing aminophosphine ligand (L = 2,6-iPr2-C6H3-NHPPh2). They cover 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 cisplatin resistant line A2780cis, while a sensitivity to non-cancer cell line MRC-5 stays very low. Mechanism of cytotoxic effect was studied in detail on one representative. It revealed up-regulation of the apoptotic proteins p38 and BAX, activation of caspase 9 and initiation of the cell apoptosis. Cell death is here accompanied with an increased amount of p21 protein and increased activity of the check point kinases, which results in the G2 arrest. Sensitivity to the cisplatin resistant cells, high selectivity to the cancer cells and activity at low dosage are the advantages of here presented Pt-Ag compounds.