Iron chelators target both proliferating and quiescent cancer cells View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-12

AUTHORS

Mårten Fryknäs, Xiaonan Zhang, Ulf Bremberg, Wojciech Senkowski, Maria Hägg Olofsson, Peter Brandt, Ingmar Persson, Padraig D'Arcy, Joachim Gullbo, Peter Nygren, Leoni Kunz Schughart, Stig Linder, Rolf Larsson

ABSTRACT

Poorly vascularized areas of solid tumors contain quiescent cell populations that are resistant to cell cycle-active cancer drugs. The compound VLX600 was recently identified to target quiescent tumor cells and to inhibit mitochondrial respiration. We here performed gene expression analysis in order to characterize the cellular response to VLX600. The compound-specific signature of VLX600 revealed a striking similarity to signatures generated by compounds known to chelate iron. Validation experiments including addition of ferrous and ferric iron in excess, EXAFS measurements, and structure activity relationship analyses showed that VLX600 chelates iron and supported the hypothesis that the biological effects of this compound is due to iron chelation. Compounds that chelate iron possess anti-cancer activity, an effect largely attributed to inhibition of ribonucleotide reductase in proliferating cells. Here we show that iron chelators decrease mitochondrial energy production, an effect poorly tolerated by metabolically stressed tumor cells. These pleiotropic features make iron chelators an attractive option for the treatment of solid tumors containing heterogeneous populations of proliferating and quiescent cells. More... »

PAGES

38343

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/srep38343

DOI

http://dx.doi.org/10.1038/srep38343

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1031532542

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27924826


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