Doxorubicin‐induced apoptosis in human T‐cell leukemia is mediated by caspase‐3 activation in a Fas‐independent way

FEBS Letters

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