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  • Fryknäs, MårtenUppsala universitet,Cancerfarmakologi och beräkningsmedicin (author)

Iron chelators target both proliferating and quiescent cancer cells

  • Article/chapterEnglish2016

Publisher, publication year, extent ...

  • 2016-12-07
  • NATURE PUBLISHING GROUP,2016
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:liu-133733
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-133733URI
  • https://doi.org/10.1038/srep38343DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:134795831URI
  • https://res.slu.se/id/publ/78343URI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-312636URI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Funding Agencies|Swedish Research Council; Knut och Alice Wallenbergs Stiftelse; Cancerforeningen in Stockholm; Cancerfonden; Vetenskapsradet; Barncancerfonden
  • 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 and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Zhang, XiaonanKarolinska 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.(Swepub:liu)xiazh59 (author)
  • Bremberg, UlfBeactica, SE-75450 Uppsala, Sweden. (author)
  • Senkowski, WojciechUppsala universitet,Cancerfarmakologi och beräkningsmedicin(Swepub:uu)wojse115 (author)
  • Hägg Olofsson, MariaKarolinska Institutet,Karolinska Inst, Dept Pathol & Oncol, Canc Ctr Karolinska, SE-17176 Stockholm, Sweden. (author)
  • Brandt, PeterUppsala universitet,Avdelningen för organisk farmaceutisk kemi(Swepub:uu)petbr436 (author)
  • Persson, IngmarSwedish 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.(Swepub:slu)49008 (author)
  • D´arcy, PadraigKarolinska Institutet,Linköpings universitet,Avdelningen för läkemedelsforskning,Medicinska fakulteten,Linkping Univ, Dept Med & Hlth Sci, SE-58183 Linkoping, Sweden.(Swepub:liu)padda29 (author)
  • Gullbo, JoachimUppsala universitet,Cancerfarmakologi och beräkningsmedicin,Experimentell och klinisk onkologi(Swepub:uu)joacgull (author)
  • Nygren, PeterUppsala universitet,Experimentell och klinisk onkologi(Swepub:uu)peterng (author)
  • Kunz Schughart, LeoniTechnical University of Dresden, Germany,Tech Univ Dresden, OncoRay Natl Ctr Radiat Res Oncol, D-01307 Dresden, Germany. (author)
  • Linder, StigKarolinska 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.(Swepub:liu)stili13 (author)
  • Larsson, RolfUppsala universitet,Cancerfarmakologi och beräkningsmedicin(Swepub:uu)rolflars (author)
  • Uppsala universitetCancerfarmakologi och beräkningsmedicin (creator_code:org_t)
  • Sveriges lantbruksuniversitet

Related titles

  • In:Scientific Reports: NATURE PUBLISHING GROUP62045-2322

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