期刊
NEW JOURNAL OF CHEMISTRY
卷 45, 期 41, 页码 19506-19514出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/d1nj03533a
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资金
- Department of Medical Biochemistry in Hradec Kralove of Charles University in Prague
- Charles University in Prague [Progres/UK Q40/01]
Two series of heterobimetallic compounds, including neutral Pt-Sn complexes and ionic Pt-Ag complexes, were synthesized and showed high cytotoxicity against ovarian cancer cells, particularly cisplatin resistant ones. Mechanistic studies revealed the induction of cell apoptosis through regulation of apoptotic proteins and activation of caspase pathways.
Two series of heterobimetallic compounds were prepared from the starting complex [cis-L2PtCl2] containing an aminophosphine ligand (L = 2,6-iPr(2)-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.
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