Defective Bax activation in Hodgkin B-cell lines confers resistance to staurosporine-induced apoptosis.
Deregulated apoptosis represents an important hallmark of tumor cells. Here we investigated the induction of cell death signaling pathways in cell lines previously established from patients with Hodgkin's disease. Our data show that Hodgkin's disease derived B-cell lines uniformly proved resistant to staurosporine, a protein kinase C inhibitor that preferentially stimulates the mitochondrial apoptotic pathway. Contrary to control cell lines, staurosporine failed to induce cytochrome c release from mitochondria in Hodgkin derived B-cells. Correspondingly, activation of caspases was not observed in these cells. In staurosporine-treated Hodgkin cells Bax remained in its inactive state, indicating that these cell lines have a defect in this crucial step in apoptotic signaling upstream of the mitochondria. Our results suggest that the failure to activate Bax might represent a common defect of Hodgkin tumor cells of the B-cell lineage.
Kashkar
H
H
Institute for Medical Microbiology, Immunology and Hygiene, University of Köln, Goldenfelsstrasse 19-21, 50935 Köln, Germany.
Krönke
M
M
Jürgensmeier
J M
JM
D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D004351:Drug Resistance; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006689:Hodgkin Disease; D006801:Humans; D008928:Mitochondria; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D015398:Signal Transduction; D019311:Staurosporine / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D004791:Enzyme Inhibitors; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D011493:Protein Kinase C; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D019311:Staurosporine