γ-Glutamyltransferase enzyme activity of cancer cells modulates L-γ-glutamyl-p-nitroanilide (GPNA) cytotoxicity View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Alessandro Corti, Silvia Dominici, Simona Piaggi, Eugenia Belcastro, Martina Chiu, Giuseppe Taurino, Simone Pacini, Ovidio Bussolati, Alfonso Pompella

ABSTRACT

L-γ-Glutamyl-p-nitroanilide (GPNA) is widely used to inhibit the glutamine (Gln) transporter ASCT2, but recent studies have demonstrated that it is also able to inhibit other sodium-dependent and independent amino acid transporters. Moreover, GPNA is a well known substrate of the enzyme γ-glutamyltransferase (GGT). Our aim was to evaluate the effect of GGT-mediated GPNA catabolism on cell viability and Gln transport. The GGT-catalyzed hydrolysis of GPNA produced cytotoxic effects in lung cancer A549 cells, resulting from the release of metabolite p-nitroaniline (PNA) rather than from the inhibition of Gln uptake. Interestingly, compounds like valproic acid, verapamil and reversan were able to increase the cytotoxicity of GPNA and PNA, suggesting a key role of intracellular detoxification mechanisms. Our data indicate that the mechanism of action of GPNA is more complex than believed, and further confirm the poor specificity of GPNA as an inhibitor of Gln transport. Different factors may modulate the final effects of GPNA, ranging from GGT and ASCT2 expression to intracellular defenses against xenobiotics. Thus, other strategies - such as a genetic suppression of ASCT2 or the identification of new specific inhibitors - should be preferred when inhibition of ASCT2 function is required. More... »

PAGES

891

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-018-37385-x

DOI

http://dx.doi.org/10.1038/s41598-018-37385-x

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1111747625

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30696905


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Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41598-018-37385-x'

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

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41598-018-37385-x'


 

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

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