Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Iron chelators target both proliferating and quiescent cancer cells
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
Linkping Univ, Dept Med & Hlth Sci, SE-58183 Linkoping, Sweden.;Karolinska Inst, Dept Pathol & Oncol, Canc Ctr Karolinska, SE-17176 Stockholm, Sweden..
Beactica, SE-75450 Uppsala, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
Show others and affiliations
2016 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 38343Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2016. Vol. 6, article id 38343
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-312636DOI: 10.1038/srep38343ISI: 000389738800001OAI: oai:DiVA.org:uu-312636DiVA, id: diva2:1066860
Funder
Swedish Research CouncilKnut and Alice Wallenberg FoundationSwedish Cancer SocietySwedish Childhood Cancer Foundation
Available from: 2017-01-19 Created: 2017-01-12 Last updated: 2017-11-29Bibliographically approved

Open Access in DiVA

fulltext(1205 kB)128 downloads
File information
File name FULLTEXT01.pdfFile size 1205 kBChecksum SHA-512
1efaf1239f84ad0788adb54ac17714b5bd182e8ceb38efff7a7b9c82df6bbadbf2c1e51f64f55d7ad600aea7d0f91dfd59cd05fe037f34bf6ffd58dbe558aae7
Type fulltextMimetype application/pdf

Other links

Publisher's full text

Search in DiVA

By author/editor
Fryknäs, MårtenSenkowski, WojciechBrandt, PeterGullbo, JoachimNygren, PeterLarsson, Rolf
By organisation
Cancer Pharmacology and Computational MedicineOrganic Pharmaceutical ChemistryExperimental and Clinical Oncology
In the same journal
Scientific Reports
Cancer and Oncology

Search outside of DiVA

GoogleGoogle Scholar
Total: 128 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 526 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf