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Celecoxib disrupts the canonical apoptotic network in HTLV-I cells through activation of Bax and inhibition of PKB/Akt

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Abstract

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive lymphoproliferative disease of very poor clinical prognosis associated with infection by the human T-cell leukemia virus type I (HTLV-I). Treatment of patients with ATLL using conventional chemotherapy has limited benefit because HTLV-I cells are refractory to most apoptosis-inducing agents. In this study, we report that Celecoxib induces cell death via the intrinsic mitochondrial pathway in HTLV-I transformed leukemia cells. Treatment with Celecoxib was associated with activation of Bax, decreased expression of Mcl-1, loss of the mitochondrial membrane potential and caspase-9-dependent apoptosis. These effects were independent from Bcl-2 and Bcl-xL. We also found that Celecoxib inhibited the Akt/GSK3 β survival pathway in HTLV-I cells.

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Acknowledgment

This work was supported by the National Cancer Institute grant CA106258 to C.N.

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Authors and Affiliations

  1. Department of Microbiology, Immunology, and Molecular Genetics, University of Kansas Medical Center, 3025 Wahl Hall West, 3901 Rainbow Blvd., Kansas City, KS, 66160, USA

    Uma Sinha-Datta, John M. Taylor, Megan Brown & Christophe Nicot

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  1. Uma Sinha-Datta
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  2. John M. Taylor
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  3. Megan Brown
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  4. Christophe Nicot
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Corresponding author

Correspondence to Christophe Nicot.

Additional information

U. Sinha-Datta and J. M. Taylor have contributed equally to this work.

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Sinha-Datta, U., Taylor, J.M., Brown, M. et al. Celecoxib disrupts the canonical apoptotic network in HTLV-I cells through activation of Bax and inhibition of PKB/Akt. Apoptosis 13, 33–40 (2008). https://doi.org/10.1007/s10495-007-0148-7

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  • DOI: https://doi.org/10.1007/s10495-007-0148-7

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