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J Cell Mol Med. 2019 Oct;23(10):7078-7087. doi: 10.1111/jcmm.14610. Epub 2019 Aug 20.

Aspirin inhibits proliferation and promotes differentiation of neuroblastoma cells via p21Waf1 protein up-regulation and Rb1 pathway modulation.

Author information

1
Institute of Pharmacology, Università Cattolica del Sacro Cuore, Rome, Italy.
2
Pharmacology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
3
Department of Cytology and Histology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt.
4
Institute of Translational Pharmacology (IFT), National Research Council (CNR), Rome, Italy.

Abstract

Several clinical and experimental studies have demonstrated that regular use of aspirin (acetylsalicylic acid, ASA) correlates with a reduced risk of cancer and that the drug exerts direct anti-tumour effects. We have previously reported that ASA inhibits proliferation of human glioblastoma multiforme-derived cancer stem cells. In the present study, we analysed the effects of ASA on nervous system-derived cancer cells, using the SK-N-SH (N) human neuroblastoma cell line as an experimental model. ASA treatment of SK-N-SH (N) dramatically reduced cell proliferation and motility, and induced neuronal-like differentiation, indicated by the appearance of the neuronal differentiation marker tyrosine hydroxylase (TH) after 5 days. ASA did not affect cell viability, but caused a time-dependent accumulation of cells in the G0 /G1 phase of the cell cycle, with a concomitant decrease in the percentage of cells in the G2 phase. These effects appear to be mediated by a COX-independent mechanism involving an increase in p21Waf1 and underphosphorylated retinoblastoma (hypo-pRb1) protein levels. These findings may support a potential role of ASA as adjunctive therapeutic agent in the clinical management of neuroblastoma.

KEYWORDS:

Rb1; acetylsalicylic acid; cell cycle; neuroblastoma; neuronal differentiation

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