Mechanisms underlying reductant-induced reactive oxygen species formation by anticancer copper(II) compounds View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-03

AUTHORS

Christian R. Kowol, Petra Heffeter, Walter Miklos, Lars Gille, Robert Trondl, Loredana Cappellacci, Walter Berger, Bernhard K. Keppler

ABSTRACT

Intracellular generation of reactive oxygen species (ROS) via thiol-mediated reduction of copper(II) to copper(I) has been assumed as the major mechanism underlying the anticancer activity of copper(II) complexes. The aim of this study was to compare the anticancer potential of copper(II) complexes of Triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone; currently in phase II clinical trials) and its terminally dimethylated derivative with that of 2-formylpyridine thiosemicarbazone and that of 2,2'-bipyridyl-6-carbothioamide. Experiments on generation of oxidative stress and the influence of biologically relevant reductants (glutathione, ascorbic acid) on the anticancer activity of the copper complexes revealed that reductant-dependent redox cycling occurred mainly outside the cells, leading to generation and dismutation of superoxide radicals resulting in cytotoxic amounts of H(2)O(2). However, without extracellular reductants only weak intracellular ROS generation was observed at IC(50) levels, suggesting that cellular thiols are not involved in copper-complex-induced oxidative stress. Taken together, thiol-induced intracellular ROS generation might contribute to the anticancer activity of copper thiosemicarbazone complexes but is not the determining factor. More... »

PAGES

409-423

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00775-011-0864-x

DOI

http://dx.doi.org/10.1007/s00775-011-0864-x

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1021572393

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22189939


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