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ORIGINAL ARTICLE

Curcumin induces apoptosis in human neuroblastoma cells via inhibition of AKT and Foxo3a nuclear translocation

, , , , &
Pages 1397-1408 | Received 19 Mar 2014, Accepted 28 Aug 2014, Published online: 06 Oct 2014
 

Abstract

Neuroblastoma (NB) is one of the most frequent extracranial solid tumors in children. It accounts for 8–10% of all childhood cancer deaths, and there is a need for development of new drugs for its treatment. Curcumin (diferuloylmethane), a major active component of turmeric (Curcuma longa), has been shown to exert anti-tumor activity on NB, but the specific mechanism by which curcumin inhibits cancer cells proliferation remains unclear. In the present study, we investigated the anti-proliferative effect of curcumin in human LAN5 NB cells. Curcumin treatment causes a rapid increase in reactive oxygen species and a decrease in the mitochondrial membrane potential—events leading to apoptosis activation. Furthermore, curcumin induces decrease in haet shock protein (Hsp)60 and hexokinase II mitochondrial protein levels and increase in the pro-apoptotic protein, bcl-2 associated death promoter (BAD). Moreover, we demonstrate that curcumin modulates anti-tumor activity through modulation of phosphatase and tensin homolog deleted on chromosome 10 and consequential inhibition of the survival Akt cell-signaling pathway. Inhibition of Akt causes its translocation into the cytoplasm and import of Foxo3a into the nucleus where it activates the expression of p27, Bim, and Fas-L pro-apoptotic genes. Together, these results take evidence for considering curcumin as a potential therapeutic agent for patients with NB.

Abbreviations
AML=

Acute Myeloid Leukemia

ANOVA=

Analysis of Variance

Akt (PKB)=

protein kinase B

BAD=

bcl-2 associated death promoter

BSA=

Bovine Serum Albumine

DCFH-DA=

dichlorofluorescein diacetate

DTT=

Dithiothreitol

5′-FU=

5′ Fluoracil

HSP=

Haet Shock Protein

HKII=

hexokinase-II

ΔΨm=

mitochondrial membrane potential

MTS=

3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium

NF-κB=

nuclear factor kappa B

PAGE=

Poly Acrilamide Gel Electrophoreses

PBS=

Phosphate Buffered Saline

PCR=

Polymerase Chain Reaction

PICT (GLTSCR2)=

Glioma Tumor Suppressor Candidate RegionGene 2

PTEN=

phosphatase and tensin homolog deleted on chromosome 10

PTP=

permeability transition pore

ROS=

reactive oxygen species

SDS=

Sodium Dodecyl Sulfate

TBST=

Tris Buffered Saline plus Tween-20

TRITC=

Tetramethyl rodamine-5(and6) isothiocyanate

Abbreviations
AML=

Acute Myeloid Leukemia

ANOVA=

Analysis of Variance

Akt (PKB)=

protein kinase B

BAD=

bcl-2 associated death promoter

BSA=

Bovine Serum Albumine

DCFH-DA=

dichlorofluorescein diacetate

DTT=

Dithiothreitol

5′-FU=

5′ Fluoracil

HSP=

Haet Shock Protein

HKII=

hexokinase-II

ΔΨm=

mitochondrial membrane potential

MTS=

3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium

NF-κB=

nuclear factor kappa B

PAGE=

Poly Acrilamide Gel Electrophoreses

PBS=

Phosphate Buffered Saline

PCR=

Polymerase Chain Reaction

PICT (GLTSCR2)=

Glioma Tumor Suppressor Candidate RegionGene 2

PTEN=

phosphatase and tensin homolog deleted on chromosome 10

PTP=

permeability transition pore

ROS=

reactive oxygen species

SDS=

Sodium Dodecyl Sulfate

TBST=

Tris Buffered Saline plus Tween-20

TRITC=

Tetramethyl rodamine-5(and6) isothiocyanate

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