title: 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.
authors.affiliation: Institute of Biomedicine and Molecular Immunlology "Alberto Monroy" (IBIM), Consiglio Nazionale delle Ricerche (CNR) , Palermo , Italy.
authors.forename: P
authors.initials: P
authors.lastname: Picone
authors.forename: D
authors.initials: D
authors.lastname: Nuzzo
authors.forename: L
authors.initials: L
authors.lastname: Caruana
authors.forename: E
authors.initials: E
authors.lastname: Messina
authors.forename: V
authors.initials: V
authors.lastname: Scafidi
authors.forename: M
authors.initials: M
authors.lastname: Di Carlo
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002467:Cell Nucleus / Q000187:drug effects* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D017382:Reactive Oxygen Species; D051057:Proto-Oncogene Proteins c-akt; D003474:Curcumin
keywords: apoptosis; curcumin; neuroblastoma; oxidative stress; signaling pathway