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Iron chelators targ...
Iron chelators target both proliferating and quiescent cancer cells
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- Fryknäs, Mårten (author)
- Uppsala universitet,Cancerfarmakologi och beräkningsmedicin
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- Zhang, Xiaonan (author)
- Karolinska Institutet,Linköpings universitet,Avdelningen för läkemedelsforskning,Medicinska fakulteten,Karolinska Institute, Sweden,Linkping Univ, Dept Med & Hlth Sci, SE-58183 Linkoping, Sweden.;Karolinska Inst, Dept Pathol & Oncol, Canc Ctr Karolinska, SE-17176 Stockholm, Sweden.
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- Bremberg, Ulf (author)
- Beactica, SE-75450 Uppsala, Sweden.
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- Senkowski, Wojciech (author)
- Uppsala universitet,Cancerfarmakologi och beräkningsmedicin
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- Hägg Olofsson, Maria (author)
- Karolinska Institutet,Karolinska Inst, Dept Pathol & Oncol, Canc Ctr Karolinska, SE-17176 Stockholm, Sweden.
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- Brandt, Peter (author)
- Uppsala universitet,Avdelningen för organisk farmaceutisk kemi
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- Persson, Ingmar (author)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för Kemi och Bioteknologi,The Department of Chemistry and Biotechnology,Swedish Univ Agr Sci, Dept Chem & Biotechnol, POB 7015, SE-75651 Uppsala, Sweden.
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- D´arcy, Padraig (author)
- Karolinska Institutet,Linköpings universitet,Avdelningen för läkemedelsforskning,Medicinska fakulteten,Linkping Univ, Dept Med & Hlth Sci, SE-58183 Linkoping, Sweden.
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- Gullbo, Joachim (author)
- Uppsala universitet,Cancerfarmakologi och beräkningsmedicin,Experimentell och klinisk onkologi
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- Nygren, Peter (author)
- Uppsala universitet,Experimentell och klinisk onkologi
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- Kunz Schughart, Leoni (author)
- Technical University of Dresden, Germany,Tech Univ Dresden, OncoRay Natl Ctr Radiat Res Oncol, D-01307 Dresden, Germany.
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- Linder, Stig (author)
- Karolinska Institutet,Linköpings universitet,Avdelningen för läkemedelsforskning,Medicinska fakulteten,Cancer Center Karolinska, Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden,Linkping Univ, Dept Med & Hlth Sci, SE-58183 Linkoping, Sweden.;Karolinska Inst, Dept Pathol & Oncol, Canc Ctr Karolinska, SE-17176 Stockholm, Sweden.
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- Larsson, Rolf (author)
- Uppsala universitet,Cancerfarmakologi och beräkningsmedicin
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(creator_code:org_t)
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- 2016-12-07
- 2016
- English.
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In: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 6
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Läkemedelskemi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medicinal Chemistry (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Biomaterialvetenskap (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Biomaterials Science (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Fryknäs, Mårten
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Zhang, Xiaonan
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Bremberg, Ulf
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Senkowski, Wojci ...
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Hägg Olofsson, M ...
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Brandt, Peter
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show more...
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Persson, Ingmar
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D´arcy, Padraig
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Gullbo, Joachim
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Nygren, Peter
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Kunz Schughart, ...
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Linder, Stig
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Larsson, Rolf
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medicinal Chemis ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Medical Biotechn ...
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and Biomaterials Sci ...
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MEDICAL AND HEAL ...
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- Articles in the publication
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Scientific Repor ...
- By the university
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Linköping University
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Karolinska Institutet
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Swedish University of Agricultural Sciences
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Uppsala University