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PI‐3K/Akt and NF‐κB/IκBα pathways are activated in Jurkat T cells in response to TRAIL treatment
Author(s) -
Zauli Giorgio,
Sancilio Silvia,
Cataldi Amelia,
Sabatini Nadia,
Bosco Domenico,
Di Pietro Roberta
Publication year - 2005
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20202
Subject(s) - jurkat cells , apoptosis , cytotoxic t cell , tumor necrosis factor alpha , programmed cell death , cytotoxicity , biology , protein kinase b , necrosis , nf κb , ly294002 , receptor , microbiology and biotechnology , cancer research , pharmacology , immunology , t cell , biochemistry , in vitro , immune system , genetics
The aim of this work was to evaluate the involvement of survival pathways in the response of Jurkat T leukaemic cells sensitive to the cytotoxic action of tumour necrosis factor (TNF)‐related apoptosis‐inducing ligand (TRAIL)/Apo2L. Jurkat T cells express TRAIL‐R2/DR5 and TRAIL‐R4/DcR2 receptors and start to die by apoptosis early (3 h) upon TRAIL administration reaching a dose‐dependent increase in the percentage of dead cells within 48 h (up to 85–90%). This increase in cell death is accompanied by a dose‐dependent significant ( P < 0.05) increase in the G 0 /G 1 phase of the cell cycle and reverted by the treatment with a broad inhibitor of caspases, z‐VAD‐fmk. Co‐treatment of the cells with inhibitors of PI‐3 kinase (LY294002) and nuclear factor kappa B (NF‐κB) (SN50) pathways leads to an earlier significantly increased cytotoxicity, respectively in the form of apoptosis and necrosis. Consistently with the data obtained with the pharmacological inhibitors, the activation and nuclear translocation of both PI‐3K and NF‐κB were observed. In summary, our results provide evidence that even in sensitive neoplastic cells TRAIL paradoxically activates pro‐survival pathways, which protect against TRAIL‐mediated death since their inhibition leads to an earlier and increased cytotoxicity. © 2004 Wiley‐Liss, Inc.