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
Interconnections between apoptotic and autophagic pathways during thiopurine-induced toxicity in cancer cells: the role of reactive oxygen species
Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Drug Research.
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.ORCID iD: 0000-0002-2809-7591
2016 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 46, p. 75616-75634Article in journal (Refereed) Published
Abstract [en]

Thiopurines (azathioprine, 6-mercaptopurine and 6-thioguanine) are a class of genotoxic drugs extensively used in the treatment of various illnesses including leukemia. Their underlying molecular mechanism of action involves the activation of apoptosis and autophagy but remains widely unclear. Here we present evidence that autophagy induction by thiopurines is a survival mechanism that antagonizes apoptosis and is involved in degrading damaged mitochondria through mitophagy. On the other hand, apoptosis is the main cell death mechanism by thiopurines as its inhibition prohibited cell death. Thus a tight interplay between apoptosis and autophagy controls cell fate in response to thiopurine treatment. Moreover, thiopurines disrupt mitochondrial function and induce a loss of the mitochondrial transmembrane potential. The involvement of the mitochondrial pathway in thiopurine-induced apoptosis was further confirmed by increased formation of reactive oxygen species (ROS). Inhibiting oxidative stress protected the cells from thiopurine-induced cell death and ROS scavenging prohibited autophagy induction by thiopurines. Our data indicate that the anticarcinogenic effects of thiopurines are mediated by complex interplay between cellular mechanisms governing redox homeostasis, apoptosis and autophagy.

Place, publisher, year, edition, pages
IMPACT JOURNALS LLC , 2016. Vol. 7, no 46, p. 75616-75634
Keywords [en]
6-thioguanine; 6-mercaptopurine; azathioprine; autophagy; apoptosis
National Category
Cell Biology
Identifiers
URN: urn:nbn:se:liu:diva-133893DOI: 10.18632/oncotarget.12313ISI: 000389632800093PubMedID: 27689330OAI: oai:DiVA.org:liu-133893DiVA, id: diva2:1065068
Note

Funding Agencies|Swedish Childhood Cancer Foundation; Medical Research Council of Southeast Sweden

Available from: 2017-01-13 Created: 2017-01-13 Last updated: 2017-11-29

Open Access in DiVA

fulltext(8973 kB)62 downloads
File information
File name FULLTEXT01.pdfFile size 8973 kBChecksum SHA-512
f15650aa607b573e79ee34bb3383b7ded3c003dd2c0e214a3fb522830ed5e6c2d09ad5cce00fabbcd853c8cf707165af0f92186cad06cbc1c884093d451abf18
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Chaabane, WiemLindqvist Appell, Malin
By organisation
Faculty of Medicine and Health SciencesDivision of Drug Research
In the same journal
OncoTarget
Cell Biology

Search outside of DiVA

GoogleGoogle Scholar
Total: 62 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
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 103 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