Apoptosis

, Volume 11, Issue 2, pp 245–254 | Cite as

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

  • A. R. Hussain
  • M. Al-Rasheed
  • P. S. Manogaran
  • K. A. Al-Hussein
  • L. C. Platanias
  • K. Al Kuraya
  • S. Uddin
Article

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.

Keywords

apoptosis AKT/PKB curcumin T cell leukemia 

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Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  • A. R. Hussain
    • 1
  • M. Al-Rasheed
    • 1
  • P. S. Manogaran
    • 2
  • K. A. Al-Hussein
    • 2
  • L. C. Platanias
    • 3
  • K. Al Kuraya
    • 1
  • S. Uddin
    • 1
    • 4
  1. 1.King Fahad National Center for Children's Cancer and ResearchKing Faisal Specialist Hospital and Research CenterSaudi Arabia
  2. 2.Biological & Medical ResearchKing Faisal Specialist Hospital and Research CenterSaudi Arabia
  3. 3.Robert H. Lurie Comprehensive Cancer CenterNorthwestern University Medical SchoolChicagoUSA
  4. 4.King Fahad National Center for Children's Cancer & ResearchKing Faisal Specialist Hospital and Research CenterRiyadhSaudi Arabia

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