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 |