Curcumin induces apoptosis via inhibition of PI3'-kinase/AKT pathway in acute T cell leukemias.
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.
Hussain
A R
AR
King Fahad National Center for Children's Cancer and Research, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Al-Rasheed
M
M
Manogaran
P S
PS
Al-Hussein
K A
KA
Platanias
L C
LC
Al Kuraya
K
K
Uddin
S
S
D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019169:Jurkat Cells; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D013997:Time Factors
D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D003474:Curcumin