Chemotherapy primes malignant glioma cells for CD95 ligand-induced apoptosis up-stream of caspase 3 activation.
The cytotoxic cytokine, CD95 ligand, is an experimental anti-cancer agent. Here, we describe a novel pathway of drug-mediated augmentation of CD95 ligand-induced apoptosis. We report that prolonged pre-exposure of human malignant glioma cells to different cytotoxic agents, VM26, cytarabine and cisplatin, induces strong sensitization to CD95 ligand-induced apoptosis. CD95 gene transfer does not prevent sensitization, suggesting that sensitization is not mediated by drug-induced CD95 expression. Priming with cytotoxic drugs greatly increases CD95 ligand-induced caspase 3 activity, indicating that the cytotoxic drugs positively modulate the CD95-dependent signalling cascade up-stream of caspase 3 activation.
Department of Neurology, University of Tübingen, School of Medicine, Germany.
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A
Hueber
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S
Winter
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M
Weller
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000201:enzymology / Q000473:pathology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D004789:Enzyme Activation; D005910:Glioma / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000378:metabolism*
D000970:Antineoplastic Agents; D019014:fas Receptor; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases