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Cross-resistance of...
Cross-resistance of CD95- and drug-induced apoptosis as a consequence of deficient activation of caspases (ICE/Ced-3 proteases)
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- Los, Marek Jan (författare)
- 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.
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- Herr, I. (författare)
- 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.
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- Friesen, C. (författare)
- 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.
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- Fulda, S. (författare)
- 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.
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- Schulze-Osthoff, K. (författare)
- 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.
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- Debatin, K. M. (författare)
- 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.
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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 (creator_code:org_t)
- American Society of Hematology, 1997
- 1997
- Engelska.
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 90:8, s. 3118-3129
- Relaterad länk:
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http://bloodjournal....
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https://liu.diva-por... (primary) (Raw object)
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Nyckelord
- 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
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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