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Issue 14, 2017
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Structurally related hydrazone-based metal complexes with different antitumor activities variably induce apoptotic cell death

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Abstract

Three new complexes bearing the tridentate hydrazone-based ligand 2-(2-(1-(pyridin-2-yl)ethylidene)hydrazinyl)pyridine (L) were synthesized and structurally characterized. Biological tests indicate that the Zn(II) complex [ZnCl2(L)] is of low cytotoxicity against the hepatocellular carcinoma cell line HepG2. In contrast, the Cu(II) and Mn(II) complexes [CuCl2(L)] and [MnCl2(L)] are highly cytotoxic with EC50 values of 1.25 ± 0.01 μM and 20 ± 1 μM, respectively. A quantitative proteome analysis reveals that treatment of the cells with the Cu(II) complex leads to a significantly altered abundance of 102 apoptosis-related proteins, whereas 38 proteins were up- or down-regulated by the Mn(II) complex. A closer inspection of those proteins regulated only by the Cu(II) complex suggests that the superior cytotoxic activity of this complex is likely to be related to an initiation of the caspase-independent cell death (CICD). In addition, an increased generation of reactive oxygen species (ROS) and a strong up-regulation of proteins responsive to oxidative stress suggest that alterations of the cellular redox metabolism likely contribute to the cytotoxicity of the Cu(II) complex.

Graphical abstract: Structurally related hydrazone-based metal complexes with different antitumor activities variably induce apoptotic cell death

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Publication details

The article was received on 06 Dec 2016, accepted on 17 Mar 2017 and first published on 17 Mar 2017


Article type: Paper
DOI: 10.1039/C6DT04613D
Citation: Dalton Trans., 2017,46, 4759-4767
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    Structurally related hydrazone-based metal complexes with different antitumor activities variably induce apoptotic cell death

    D. A. Megger, K. Rosowski, C. Radunsky, J. Kösters, B. Sitek and J. Müller, Dalton Trans., 2017, 46, 4759
    DOI: 10.1039/C6DT04613D

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