Oncotarget

Research Papers:

N-acetylaspartate (NAA) induces neuronal differentiation of SH-SY5Y neuroblastoma cell line and sensitizes it to chemotherapeutic agents

Carmela Mazzoccoli, Vitalba Ruggieri, Tiziana Tataranni, Francesca Agriesti, Ilaria Laurenzana, Angelo Fratello, Nazzareno Capitanio and Claudia Piccoli _

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Oncotarget. 2016; 7:26235-26246. https://doi.org/10.18632/oncotarget.8454

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Abstract

Carmela Mazzoccoli1, Vitalba Ruggieri1, Tiziana Tataranni1, Francesca Agriesti1, Ilaria Laurenzana1, Angelo Fratello2, Nazzareno Capitanio2, Claudia Piccoli1,2

1Laboratory of Pre-Clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture, Pz, Italy

2Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy

Correspondence to:

Claudia Piccoli, email: [email protected]

Keywords: N-acetylaspartate, neuroblastoma, cell differentiation, chemotherapy

Received: February 01, 2016     Accepted: March 10, 2016     Published: March 29, 2016

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.


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