NRF2 Mediates Neuroblastoma Proliferation and Resistance to Retinoic Acid Cytotoxicity in a Model of In Vitro Neuronal Differentiation View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2016-11

AUTHORS

Vitor de Miranda Ramos, Alfeu Zanotto-Filho, Matheus Augusto de Bittencourt Pasquali, Karina Klafke, Juciano Gasparotto, Peter Dunkley, Daniel Pens Gelain, José Cláudio Fonseca Moreira

ABSTRACT

Retinoic acid (RA) morphogenetic properties have been used in different kinds of therapies, from neurodegenerative disorders to some types of cancer such as promyelocytic leukemia and neuroblastoma. However, most of the pathways responsible for RA effects remain unknown. To investigate such pathways, we used a RA-induced differentiation model in the human neuroblastoma cells, SH-SY5Y. Our data showed that n-acetyl-cysteine (NAC) reduced cells' proliferation rate and increased cells' sensitivity to RA toxicity. Simultaneously, NAC pre-incubation attenuated nuclear factor erythroid 2-like factor 2 (NRF2) activation by RA. None of these effects were obtained with Trolox® as antioxidant, suggesting a cysteine signalization by RA. NRF2 knockdown increased cell sensibility to RA after 96 h of treatment and diminished neuroblastoma proliferation rate. Conversely, NRF2 overexpression limited RA anti-proliferative effects and increased cell proliferation. In addition, a rapid and non-genomic activation of the ERK 1/2 and PI3K/AKT pathways revealed to be equally required to promote NRF2 activation and necessary for RA-induced differentiation. Together, we provide data correlating NRF2 activity with neuroblastoma proliferation and resistance to RA treatments; thus, this pathway could be a potential target to optimize neuroblastoma chemotherapeutic response as well as in vitro neuronal differentiation protocols. More... »

PAGES

6124-6135

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s12035-015-9506-6

DOI

http://dx.doi.org/10.1007/s12035-015-9506-6

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1036065036

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26541884


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Turtle is a human-readable linked data format.

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RDF/XML is a standard XML format for linked data.

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This table displays all metadata directly associated to this object as RDF triples.

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