PI-3K/Akt and NF-κB/IκBα pathways are activated in Jurkat T cells in response to TRAIL treatment

Giorgio Zauli, Silvia Sancilio, Amelia Cataldi, Nadia Sabatini, Domenico Bosco, Roberta Di Pietro

Research output: Contribution to journalArticle

Abstract

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 G0/G1 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.

Original languageEnglish
Pages (from-to)900-911
Number of pages12
JournalJournal of Cellular Physiology
Volume202
Issue number3
DOIs
Publication statusPublished - Mar 2005

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

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    Zauli, G., Sancilio, S., Cataldi, A., Sabatini, N., Bosco, D., & Di Pietro, R. (2005). PI-3K/Akt and NF-κB/IκBα pathways are activated in Jurkat T cells in response to TRAIL treatment. Journal of Cellular Physiology, 202(3), 900-911. https://doi.org/10.1002/jcp.20202