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Iron chelators target both proliferating and quiescent cancer cells

Fryknäs, Mårten and Zhang, Xiaonan and Bremberg, Ulf and Senkowski, Wojciech and Hägg Olofsson, Maria and Brandt, Peter and Persson, Ingmar and D’Arcy, Padraig and Gullbo, Joachim and Nygren, Peter and Kunz Schughart, Leoni and Linder, Stig and Larsson, Rolf (2016). Iron chelators target both proliferating and quiescent cancer cells. Scientific Reports. 6, 1-11
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Official URL: http://dx.doi.org/10.1038/srep38343

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.

Authors/Creators:Fryknäs, Mårten and Zhang, Xiaonan and Bremberg, Ulf and Senkowski, Wojciech and Hägg Olofsson, Maria and Brandt, Peter and Persson, Ingmar and D’Arcy, Padraig and Gullbo, Joachim and Nygren, Peter and Kunz Schughart, Leoni and Linder, Stig and Larsson, Rolf
Title:Iron chelators target both proliferating and quiescent cancer cells
Series/Journal:Scientific Reports (2045-2322)
Year of publishing :2016
Volume:6
Page range:1-11
Number of Pages:11
Publisher:Nature Publishing Group
ISSN:2045-2322
Language:English
Publication Type:Journal article
Refereed:Yes
Article category:Scientific peer reviewed
Version:Published version
Full Text Status:Public
Agris subject categories.:X Agricola extesions > X50 Chemistry
Subjects:(A) Swedish standard research categories 2011 > 3 Medical and Health Sciences > 301 Basic Medicine > Medicinal Chemistry
(A) Swedish standard research categories 2011 > 3 Medical and Health Sciences > 304 Medical Biotechnology > Biomaterials Science
Keywords:Iron(II) chelate, cancer, therapy, proliferating cells, quiescent cells
URN:NBN:urn:nbn:se:slu:epsilon-e-3872
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-e-3872
ID Code:13917
Faculty:NJ - Fakulteten för naturresurser och jordbruksvetenskap
Department:(NL, NJ) > Department of Chemistry and Biotechnology (140101-161231)
Deposited By: SLUpub Connector
Deposited On:09 Jan 2017 12:53
Metadata Last Modified:14 Jun 2017 10:58

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