liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • 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
Cross-resistance of CD95- and drug-induced apoptosis as a consequence of deficient activation of caspases (ICE/Ced-3 proteases)
Hematology/Oncology, University Children's Hospital, and the Division of Molecular Oncology, German Cancer Research Center, Heidelberg, Germany; and the Institute of Biochemistry, University of Freiburg, Freiburg, Germany. .ORCID iD: 0000-0001-9518-1411
Hematology/Oncology, University Children's Hospital, and the Division of Molecular Oncology, German Cancer Research Center, Heidelberg, Germany; and the Institute of Biochemistry, University of Freiburg, Freiburg, Germany. .
Hematology/Oncology, University Children's Hospital, and the Division of Molecular Oncology, German Cancer Research Center, Heidelberg, Germany; and the Institute of Biochemistry, University of Freiburg, Freiburg, Germany. .
Hematology/Oncology, University Children's Hospital, and the Division of Molecular Oncology, German Cancer Research Center, Heidelberg, Germany; and the Institute of Biochemistry, University of Freiburg, Freiburg, Germany. .
Show others and affiliations
1997 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 90, no 8, 3118-3129 p.Article in journal (Refereed) Published
Abstract [en]

The cytotoxic effect of anticancer drugs has been shown to involve induction of apoptosis. We report here that tumor cells resistant to CD95 (APO-1/Fas) -mediated apoptosis were cross-resistant to apoptosis-induced by anticancer drugs. Apoptosis induced in tumor cells by cytarabine, doxorubicin, and methotrexate required the activation of ICE/Ced-3 proteases (caspases), similarly to the CD95 system, After drug treatment, a strong increase of caspase activity was found that preceded cell death, Drug-induced activation of caspases was also found in ex vivo-derived T-cell leukemia cells. Resistance to cell death was conferred by a peptide caspase inhibitor and CrmA, a poxvirus-derived serpin, The peptide inhibitor was effective even if added several hours after drug treatment, indicating a direct involvement of caspases in the execution and not in the trigger phase of drug action. Drug-induced apoptosis was also strongly inhibited by antisense approaches targeting caspase-1 and -3, indicating that several members of this protease family were involved. CD95-resistant cell lines that failed to activate caspases upon CD95 triggering were cross-resistant to drug-mediated apoptosis, Our data strongly support the concept that sensitivity for drug-induced cell death depends on intact apoptosis pathways leading to activation of caspases. The identification of defects in caspase activation may provide molecular targets to overcome drug resistance in tumor cells. (C) 1997 by The American Society of Hematology.

Place, publisher, year, edition, pages
American Society of Hematology , 1997. Vol. 90, no 8, 3118-3129 p.
Keyword [en]
cysteine protease, fas-mediated apoptosis, ice-like protease, il-1-beta-converting enzyme, interleukin-1-beta converting-enzyme, mammalian homolog, monoclonal-antibody, poly(adp-ribose) polymerase, programmed cell-death, signaling complex
National Category
Hematology Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:liu:diva-87070ISI: A1997YC73600027PubMedID: 9376593OAI: oai:DiVA.org:liu-87070DiVA: diva2:584790
Available from: 2013-01-09 Created: 2013-01-09 Last updated: 2017-12-06

Open Access in DiVA

fulltext(317 kB)546 downloads
File information
File name FULLTEXT01.pdfFile size 317 kBChecksum SHA-512
58cf0970bfb56daf16953802d25d87a64d5bebf748c8e77d09e1155a6f11ce617d5f00357d993c6f099acfc8d503300bf3d6e1c955537de50ff57d7b3b5ea57b
Type fulltextMimetype application/pdf

Other links

PubMedLink to article

Authority records BETA

Los, Marek Jan

Search in DiVA

By author/editor
Los, Marek Jan
In the same journal
Blood
HematologyBiochemistry and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar
Total: 546 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

pubmed
urn-nbn

Altmetric score

pubmed
urn-nbn
Total: 286 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • 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