title: N-acetylaspartate (NAA) induces neuronal differentiation of SH-SY5Y neuroblastoma cell line and sensitizes it to chemotherapeutic agents.
abstract: Neuroblastoma is the most commonly extra-cranial solid tumor of childhood frequently diagnosed. The nervous system-specific metabolite N-acetylaspartate (NAA) is synthesized from aspartate and acetyl-CoA in neurons, it is among the most abundant metabolites present in the central nervous system (CNS) and appears to be involved in many CNS disorders. The functional significance of the high NAA concentration in the brain remains uncertain, but it confers to NAA a unique clinical significance exploited in magnetic resonance spectroscopy. In the current study, we show that treatment of SH-SY5Y neuroblastoma-derived cell line with sub-cytotoxic physiological concentrations of NAA inhibits cell growth. This effect is partly due to enhanced apoptosis, shown by decrease of the anti-apoptotic factors survivin and Bcl-xL, and partly to arrest of the cell-cycle progression, linked to enhanced expression of the cyclin-inhibitors p53, p21Cip1/Waf1 and p27Kip1. Moreover, NAA-treated SH-SY5Y cells exhibited morphological changes accompanied with increase of the neurogenic markers TH and MAP2 and down-regulation of the pluripotency markers OCT4 and CXCR4/CD184. Finally, NAA-pre-treated SH-SY5Y cells resulted more sensitive to the cytotoxic effect of the chemotherapeutic drugs Cisplatin and 5-fluorouracil.To our knowledge, this is the first study demonstrating the neuronal differentiating effects of NAA in neuroblastoma cells. NAA may be a potential preconditioning or adjuvant compound in chemotherapeutic treatment.
authors.affiliation: Laboratory of Pre-Clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture, Pz, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Mazzoccoli
authors.affiliation: Laboratory of Pre-Clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture, Pz, Italy.
authors.forename: Vitalba
authors.initials: V
authors.lastname: Ruggieri
authors.affiliation: Laboratory of Pre-Clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture, Pz, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Tataranni
authors.affiliation: Laboratory of Pre-Clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture, Pz, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Agriesti
authors.affiliation: Laboratory of Pre-Clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture, Pz, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Laurenzana
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Fratello
authors.affiliation: Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
authors.forename: Nazzareno
authors.initials: N
authors.lastname: Capitanio
authors.affiliation: Laboratory of Pre-Clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture, Pz, Italy.|Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Piccoli
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D009447:Neuroblastoma / Q000473:pathology*; D009474:Neurons / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D001224:Aspartic Acid; C000179:N-acetylaspartate
keywords: N-acetylaspartate; cell differentiation; chemotherapy; neuroblastoma