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Doxorubicin‐induced apoptosis in human T‐cell leukemia is mediated by caspase‐3 activation in a Fas‐independent way
Author(s) -
Gamen Susana,
Anel Alberto,
Lasierra Pilar,
Alava Marı́a A,
Martinez-Lorenzo Maria José,
Piñeiro Andrés,
Naval Javier
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)01282-9
Subject(s) - fas ligand , apoptosis , jurkat cells , autocrine signalling , fas receptor , caspase , programmed cell death , caspase 8 , cancer research , intrinsic apoptosis , biology , microbiology and biotechnology , doxorubicin , leukemia , chemistry , cell culture , immunology , t cell , biochemistry , chemotherapy , immune system , genetics
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.