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Curcumin induces apoptosis via inhibition of PI3′-kinase/AKT pathway in Acute T cell Leukemias

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Abstract

Curcumin has been shown to possess variety of biological functions including anti-tumor activity. The mechanism by which curcumin inhibit cell proliferation remains poorly understood. In the present report, we investigated the effect of curcumin on the activation of apoptotic pathway in T-cell acute lymphoblastic leukemia (T-ALL) malignant cells. Our data demonstrate that curcumin causes dose dependent suppression of proliferation in several T cell lines. Curcumin treatment causes the de-phosphorylation/inactivation of constitutively active AKT, FOXO transcription factor and GSK3. Curcumin also induces release of cytochrome c accompanied by activation of caspase-3 and PARP cleavage. In addition, zVAD-fmk, a universal inhibitor of caspases, prevents caspase-3 activation and abrogates cell death induced by curcumin treatment. Finally, treatment of T-ALL cells with curcumin down-regulated the expression of inhibitor of apoptosis protein (IAPs). Taken together, our finding suggest that curcumin suppresses constitutively activated targets of PI3′-kinase (AKT, FOXO and GSK3) in T cells leading to the inhibition of proliferation and induction of caspase-dependent apoptosis.

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Authors and Affiliations

  1. King Fahad National Center for Children's Cancer and Research, King Faisal Specialist Hospital and Research Center, Saudi Arabia

    A. R. Hussain, M. Al-Rasheed, K. Al Kuraya & S. Uddin

  2. Biological & Medical Research, King Faisal Specialist Hospital and Research Center, Saudi Arabia

    P. S. Manogaran & K. A. Al-Hussein

  3. Robert H. Lurie Comprehensive Cancer Center, Northwestern University Medical School, Chicago, Illinois, USA

    L. C. Platanias

  4. King Fahad National Center for Children's Cancer & Research, King Faisal Specialist Hospital and Research Center, MBC #98-16, P.O Box 3354, Riyadh, 11211, Saudi Arabia

    S. Uddin

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  1. A. R. Hussain
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  2. M. Al-Rasheed
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  3. P. S. Manogaran
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  4. K. A. Al-Hussein
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  5. L. C. Platanias
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  6. K. Al Kuraya
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  7. S. Uddin
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Correspondence to S. Uddin.

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Hussain, A.R., Al-Rasheed, M., Manogaran, P.S. et al. Curcumin induces apoptosis via inhibition of PI3′-kinase/AKT pathway in Acute T cell Leukemias. Apoptosis 11, 245–254 (2006). https://doi.org/10.1007/s10495-006-3392-3

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  • DOI: https://doi.org/10.1007/s10495-006-3392-3

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