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

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.

journal_name

Free Radic Res

journal_title

Free radical research

authors

Picone P,Nuzzo D,Caruana L,Messina E,Scafidi V,Di Carlo M

doi

10.3109/10715762.2014.960410

subject

Has Abstract

pub_date

2014-12-01 00:00:00

pages

1397-408

issue

12

eissn

1071-5762

issn

1029-2470

journal_volume

48

pub_type

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