1. Doxorubicin-induced apoptosis in human T-cell leukemia is mediated by caspase-3 activation in a Fas-independent way.
- Author
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Gamen S, Anel A, Lasierra P, Alava MA, Martinez-Lorenzo MJ, Piñeiro A, and Naval J
- Subjects
- Annexin A5 physiology, Antibodies pharmacology, Apoptosis drug effects, Caspase 3, Cell Line, Cysteine Endopeptidases biosynthesis, Dactinomycin pharmacology, Enzyme Activation, Enzyme Induction, Enzyme Precursors metabolism, Fas Ligand Protein, Humans, Jurkat Cells cytology, Jurkat Cells drug effects, Lymphoma, T-Cell, Membrane Glycoproteins immunology, Membrane Glycoproteins physiology, Methotrexate pharmacology, Vincristine pharmacology, fas Receptor physiology, Apoptosis physiology, Caspases, Cysteine Endopeptidases metabolism, Doxorubicin toxicity, Jurkat Cells physiology
- Abstract
It has recently been proposed that doxorubicin (DOX) can induce apoptosis in human T-leukemia cells via the Fas/FasL system in an autocrine/paracrine way. We show here that treatment of Jurkat cells with either anti-Fas antibodies, anthracyclin drugs or actinomycin D induces the activation of CPP32 (caspase-3) and apoptosis. However, DOX treatment did not induce the expression of membrane FasL or the release of soluble FasL and co-incubation with blocking anti-Fas antibodies prevented Fas-induced but not DOX-induced apoptosis. All the morphological and biochemical signs of apoptosis induced by anti-Fas or DOX can be prevented by Z-VAD-fmk, a general caspase inhibitor. DEVD-cho, a specific inhibitor of CPP32-like caspases which completely blocks Fas-mediated apoptosis, prevented drug-induced nuclear apoptosis but not cell death. We conclude that: (i) DOX-induced apoptosis in human T-leukemia/lymphoma is Fas-independent and (ii) caspase-3 is responsible of DOX-induced nuclear apoptosis but other Z-VAD-sensitive caspases are implicated in cell death.
- Published
- 1997
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