Involvement of ICE-Like Proteases in Gemcitabine-Induced Programmed Cell Death
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.
KeywordsCysteine Protease Gemcitabine Treatment Methyl Coumarin Dent Protein Kinase Gemcitabine Induce Apoptosis
Unable to display preview. Download preview PDF.
- 12.Casciola-Rolen L, Miller DK, Anhalt GJ, Rosen A (1994) Specific cleavage of the 70-kDA protein component of the Ul small nuclear ribonucleaprotein is a characteristic biochemical feature of apoptotic cell death. J Biol Chem 269: 30757–30760Google Scholar