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*

*Corresponding author for this work

Research output: Contribution to journalArticle

144 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)245-254
Number of pages10
JournalApoptosis
Volume11
Issue number2
DOIs
StatePublished - Feb 1 2006

Keywords

  • AKT/PKB
  • Apoptosis
  • Curcumin
  • T cell leukemia

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Cancer Research

Fingerprint Dive into the research topics of 'Curcumin induces apoptosis via inhibition of PI3′-kinase/AKT pathway in acute T cell leukemias'. Together they form a unique fingerprint.

  • Cite this

    Hussain, A. R., Al-Rasheed, M., Manogaran, P. S., Al-Hussein, K. A., Platanias, L. C., Al Kuraya, K., & Uddin, S. (2006). Curcumin induces apoptosis via inhibition of PI3′-kinase/AKT pathway in acute T cell leukemias. Apoptosis, 11(2), 245-254. https://doi.org/10.1007/s10495-006-3392-3