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

Neuroblastoma is one of the most frequent extra cranial solid tumors in children. It accounts for 8-10% of all childhood cancer deaths and development of new drugs for its treatment results to be needed. Curcumin (diferuloylmethane) a major active component of tumeric (Curcuma longa) has been shown to exert anti-tumor activity on neuroblastoma, but the specific mechanism by which curcumin inhibits cancer cells proliferation remains unclear. In the present studies we investigated the anti-proliferative effect of curcumin in human LAN5 neuroblastoma cells. Curcumin treatment causes a rapid increase of reactive oxygen species (ROS) and a decrease of the mitochondrial membrane potential, events leading to apoptosis activation. Furthermore, curcumin induces decrease in Hsp60 and hexokinase II (HkII) mitochondrial protein levels and increase of the pro-apoptotic protein BAD. Moreover, we demonstrate that curcumin modulates antitumor activity through modulation of PTEN and consequential inhibition of the survival Akt cell-signaling pathway. Inhibition of Akt causes its translocation into the cytoplasm and importing of Foxo3a into the nucleus where activates the expression of p27, Bim, Fas-L pro-apoptotic genes. Together, these results take evidence for considering curcumin as a potential therapeutic agent for patients with neuroblastoma.