Issue 14, 2017

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

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

Supplementary files

Article information

Article type
Paper
Submitted
06 Dec 2016
Accepted
17 Mar 2017
First published
17 Mar 2017

Dalton Trans., 2017,46, 4759-4767

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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