{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T05:18:35Z","timestamp":1790918315337,"version":"4.1.0"},"reference-count":50,"publisher":"American Society of Hematology","issue":"5","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,3,1]]},"abstract":"<jats:p>The activation of caspase-8, a crucial upstream mediator of death receptor signaling, was investigated in epirubicin- and Taxol-induced apoptosis of B-lymphoma cells. This study was performed because the CD95\/Fas receptor-ligand interaction, recruitment of the Fas-associated death domain (FADD) adaptor protein, and subsequent activation of procaspase-8 have been implicated in the execution of drug-induced apoptosis in other cell types. Indeed, active caspase-8 was readily detected after treatment of mature and immature B-lymphoid cells with epirubicin or Taxol. However, neither constitutive nor drug-induced expression of the CD95\/Fas ligand was detectable in B-lymphoma cells. Furthermore, overexpression of a dominant-negative FADD mutant (FADDdn) did not block caspase-8 processing and subsequent DNA fragmentation, indicating that drug-induced caspase-8 activation was mediated by a CD95\/Fas-independent mechanism. Instead, caspase-8 cleavage was slightly preceded by activation of caspase-3, suggesting that drug-induced caspase-8 activation in B-lymphoma cells is a downstream event mediated by other caspases. This assumption was confirmed in 2 experimental systems\u2014zDEVD-fmk, a cell-permeable inhibitor of caspase-3\u2013like activity, blocked drug-induced caspase-8 cleavage, and depletion of caspase-3 from cell extracts impaired caspase-8 cleavage after in vitro activation with dATP and cytochrome c. Thus, these data indicate that drug-induced caspase-8 activation in B-lymphoma cells is independent of death receptor signaling and is mediated by postmitochondrial caspase-3 activation.<\/jats:p>","DOI":"10.1182\/blood.v97.5.1378","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T12:46:47Z","timestamp":1027774007000},"page":"1378-1387","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":211,"title":["Activation of caspase-8 in drug-induced apoptosis of B-lymphoid cells is independent of CD95\/Fas receptor-ligand interaction and occurs downstream of caspase-3"],"prefix":"10.1182","volume":"97","author":[{"given":"Thomas","family":"Wieder","sequence":"first","affiliation":[{"name":"From the Department of Hematology, Oncology and Tumor Immunology, University Medical Center Charite\u0301, Campus Berlin-Buch, and the Department of Pediatric Hematology\/Oncology, University Medical Center Charite\u0301, Campus Virchow, Humboldt University of Berlin, Germany; the Department of Immunology and Cell Biology, University of Mu\u0308nster, Germany; the Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology, and University of Gent, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Essmann","sequence":"additional","affiliation":[{"name":"From the Department of Hematology, Oncology and Tumor Immunology, University Medical Center Charite\u0301, Campus Berlin-Buch, and the Department of Pediatric Hematology\/Oncology, University Medical Center Charite\u0301, Campus Virchow, Humboldt University of Berlin, Germany; the Department of Immunology and Cell Biology, University of Mu\u0308nster, Germany; the Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology, and University of Gent, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aram","family":"Prokop","sequence":"additional","affiliation":[{"name":"From the Department of Hematology, Oncology and Tumor Immunology, University Medical Center Charite\u0301, Campus Berlin-Buch, and the Department of Pediatric Hematology\/Oncology, University Medical Center Charite\u0301, Campus Virchow, Humboldt University of Berlin, Germany; the Department of Immunology and Cell Biology, University of Mu\u0308nster, Germany; the Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology, and University of Gent, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Schmelz","sequence":"additional","affiliation":[{"name":"From the Department of Hematology, Oncology and Tumor Immunology, University Medical Center Charite\u0301, Campus Berlin-Buch, and the Department of Pediatric Hematology\/Oncology, University Medical Center Charite\u0301, Campus Virchow, Humboldt University of Berlin, Germany; the Department of Immunology and Cell Biology, University of Mu\u0308nster, Germany; the Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology, and University of Gent, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Schulze-Osthoff","sequence":"additional","affiliation":[{"name":"From the Department of Hematology, Oncology and Tumor Immunology, University Medical Center Charite\u0301, Campus Berlin-Buch, and the Department of Pediatric Hematology\/Oncology, University Medical Center Charite\u0301, Campus Virchow, Humboldt University of Berlin, Germany; the Department of Immunology and Cell Biology, University of Mu\u0308nster, Germany; the Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology, and University of Gent, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudi","family":"Beyaert","sequence":"additional","affiliation":[{"name":"From the Department of Hematology, Oncology and Tumor Immunology, University Medical Center Charite\u0301, Campus Berlin-Buch, and the Department of Pediatric Hematology\/Oncology, University Medical Center Charite\u0301, Campus Virchow, Humboldt University of Berlin, Germany; the Department of Immunology and Cell Biology, University of Mu\u0308nster, Germany; the Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology, and University of Gent, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Do\u0308rken","sequence":"additional","affiliation":[{"name":"From the Department of Hematology, Oncology and Tumor Immunology, University Medical Center Charite\u0301, Campus Berlin-Buch, and the Department of Pediatric Hematology\/Oncology, University Medical Center Charite\u0301, Campus Virchow, Humboldt University of Berlin, Germany; the Department of Immunology and Cell Biology, University of Mu\u0308nster, Germany; the Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology, and University of Gent, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter T.","family":"Daniel","sequence":"additional","affiliation":[{"name":"From the Department of Hematology, Oncology and Tumor Immunology, University Medical Center Charite\u0301, Campus Berlin-Buch, and the Department of Pediatric Hematology\/Oncology, University Medical Center Charite\u0301, Campus Virchow, Humboldt University of Berlin, Germany; the Department of Immunology and Cell Biology, University of Mu\u0308nster, Germany; the Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology, and University of Gent, 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