FEBS Letters | |
Doxorubicin‐induced apoptosis in human T‐cell leukemia is mediated by caspase‐3 activation in a Fas‐independent way | |
Naval, Javier2  Alava, Marı́a A2  Piñeiro, Andrés2  Martinez-Lorenzo, Maria José2  Gamen, Susana2  Anel, Alberto2  Lasierra, Pilar1  | |
[1] Servicio de Inmunologı́a, Hospital Clı́nico Universitario, Universidad de Zaragoza, Zaragoza, Spain;Departamento de Bioquı́mica y Biologia Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, 50009 Zaragoza, Spain | |
关键词: Fas; Caspase; CPP32; Chemotherapeutic drug; Apoptosis; Leukemia; FasL; Fas ligand; PS; phosphatidylserine; MTT; 3-[4; 5-dimethylthiazol-2-yl]-2; 5-diphenyl-tetrazolium bromide; DOX; doxorubicin; DEVD-cho; N-acetyl-Asp-Glu-Val-Asp aldehyde; Z-VAD-fmk; benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone; | |
DOI : 10.1016/S0014-5793(97)01282-9 | |
学科分类:生物化学/生物物理 | |
来源: John Wiley & Sons Ltd. | |
【 摘 要 】
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.
【 授权许可】
Unknown
【 预 览 】
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