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Involvement of ICE-Like Proteases in Gemcitabine-Induced Programmed Cell Death

  • O. J. Stoetzer
  • A. Pogrebniak
  • V. Heinemann
  • U. Gullis
  • M. Darsow
  • M. Zabel
  • M. Arning
  • W. Wilmanns
  • V. Nüssler
Conference paper
Part of the Haematology and Blood Transfusion / Hämatologie und Bluttransfusion book series (HAEMATOLOGY, volume 39)

Abstract

Activation of ICE-like-protease cascade is a crucial step in Fas/APO-1 (CD95) induced apoptosis in different cell lines. Here we determined the role of interleukin-1 ß-converting enzyme (ICE) and CPP32/YAMA in gemcitabine induced apoptosis in leukemic cell lines. Gemcitabine (dFdc) is a purin analog, that induces typical features of apoptosis in several leukemic lines.

After starting gemcitabine incubation CCRF-CEM cells exhibited an 9-fold increase in CPP32-activity and an 3.5-fold increase in ICE-activity. In HL-60 CPP32 activity increased 15-fold and ICE an 2-fold after gemcitabine. Preincubation with ICE- and CPP-inhibitory peptides mainly prevented enzyme activation. However, survival was not affected by inhibiting ICE and CPP32. We therefore concluded that either CPP32 and ICE-function is not essential for gemcitabine induced apoptosis or other members of the ICE-family res. other proteases take over proteolytic function.

Keywords

Cysteine Protease Gemcitabine Treatment Methyl Coumarin Dent Protein Kinase Gemcitabine Induce Apoptosis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • O. J. Stoetzer
    • 1
    • 2
  • A. Pogrebniak
    • 2
  • V. Heinemann
    • 1
  • U. Gullis
    • 2
  • M. Darsow
    • 2
  • M. Zabel
    • 1
  • M. Arning
    • 3
  • W. Wilmanns
    • 1
    • 2
  • V. Nüssler
    • 1
    • 2
  1. 1.Department of Hematology/Oncology, Klinikum GrosshadernLudwig-Maximilians-UniversityMunichGermany
  2. 2.GSF-Research CenterInstitute for Clinical HematologyMunichGermany
  3. 3.Lilly Deutschland GmbHBad HomburgGermany

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