CYTOTOXICITY OF CATIONIC DINUCLEAR PLATINUM(II) COMPLEXES IN AN EXPERIMENTAL MODEL OF MOUSE COLON CANCER

Abstract

The series of nine dinuclear platinum(II) complexes, [{Pt(L)Cl}2(μ-X)]2+ (where L is two NH3 or bidentantly coordinated diamine ligand – ethylenediamine, en; (±)-1,2-propylenediamine, 1,2-pn; isobutylenediamine, ibn; trans-(±)-1,2-diaminocyclohexane, dach; 1,3-propylenediamine, 1,3-pd; 2,2- dimethyl-1,3-propylenediamine, 2,2-diMe-1,3-pd; (±)-1,3-pentanediamine,1,3-pnd, and X is a bridging pyrazine (pz) or pyridazine (pydz) ligand) have been synthesized and characterized. The antitumor potential of these complexes against CT26 cells were determined by in vitro and in vivo assays. A murine model of heterotopic colon cancer tumor was induced in immunocompetent BALB/c mice for investigating antitumor potential of the Pt(II) complexes in vivo. It was found that complexes Pt1, Pt2 and Pt7 shows significant in vitro cytotoxic activity against mouse colon carcinoma CT26 cells, while all these complexes show moderate apoptotic effect. Complexes Pt1 and Pt7 arrested CT26 cells in G2/M phase of cell cycle, while complexes Pt5 and Pt6 exerted the highest antiproliferative effect which was evaluated by detection of Ki67 expressing cells. Complexes Pt1 and Pt2 performed significant in vivo antitumor effects reducing the growth of primary tumor and the incidence of lung and liver metastases without causing the significant hepato- and nephro- toxicity.