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Article

Cytosolic 5′-Nucleotidase II Silencing in a Human Lung Carcinoma Cell Line Opposes Cancer Phenotype with a Concomitant Increase in p53 Phosphorylation

by
Rossana Pesi
1,†,
Edoardo Petrotto
1,†,
Laura Colombaioni
2,
Simone Allegrini
1,
Mercedes Garcia-Gil
3,
Marcella Camici
1,
Lars Petter Jordheim
4 and
Maria Grazia Tozzi
1,*
1
Unità di Biochimica, Dipartimento di Biologia, Università di Pisa, Via San Zeno 51, 56127 Pisa, Italy
2
Istituto di Neuroscienze, CNR, Via Giuseppe Moruzzi 1, 56124 Pisa, Italy
3
Unità Fisiologia Generale, Dipartimento di Biologia, Università di Pisa, Via San Zeno 31, 56127 Pisa, Italy
4
Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon 69008, France
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2018, 19(7), 2115; https://doi.org/10.3390/ijms19072115
Submission received: 14 June 2018 / Revised: 17 July 2018 / Accepted: 18 July 2018 / Published: 20 July 2018
(This article belongs to the Special Issue Alterations to Signalling Pathways in Cancer Cells 2018)

Abstract

Purine homeostasis is maintained by a purine cycle in which the regulated member is a cytosolic 5′-nucleotidase II (cN-II) hydrolyzing IMP and GMP. Its expression is particularly high in proliferating cells, indeed high cN-II activity or expression in hematological malignancy has been associated to poor prognosis and chemoresistance. Therefore, a strong interest has grown in developing cN-II inhibitors, as potential drugs alone or in combination with other compounds. As a model to study the effect of cN-II inhibition we utilized a lung carcinoma cell line (A549) in which the enzyme was partially silenced and its low activity conformation was stabilized through incubation with 2-deoxyglucose. We measured nucleotide content, reduced glutathione, activities of enzymes involved in glycolysis and Krebs cycle, protein synthesis, mitochondrial function, cellular proliferation, migration and viability. Our results demonstrate that high cN-II expression is associated with a glycolytic, highly proliferating phenotype, while silencing causes a reduction of proliferation, protein synthesis and migration ability, and an increase of oxidative performances. Similar results were obtained in a human astrocytoma cell line. Moreover, we demonstrate that cN-II silencing is concomitant with p53 phosphorylation, suggesting a possible involvement of this pathway in mediating some of cN-II roles in cancer cell biology.
Keywords: Cytosolic 5′-nucleotidase; p53; 2-deoxyglucose; human lung carcinoma; cell proliferation Cytosolic 5′-nucleotidase; p53; 2-deoxyglucose; human lung carcinoma; cell proliferation
Graphical Abstract

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MDPI and ACS Style

Pesi, R.; Petrotto, E.; Colombaioni, L.; Allegrini, S.; Garcia-Gil, M.; Camici, M.; Jordheim, L.P.; Tozzi, M.G. Cytosolic 5′-Nucleotidase II Silencing in a Human Lung Carcinoma Cell Line Opposes Cancer Phenotype with a Concomitant Increase in p53 Phosphorylation. Int. J. Mol. Sci. 2018, 19, 2115. https://doi.org/10.3390/ijms19072115

AMA Style

Pesi R, Petrotto E, Colombaioni L, Allegrini S, Garcia-Gil M, Camici M, Jordheim LP, Tozzi MG. Cytosolic 5′-Nucleotidase II Silencing in a Human Lung Carcinoma Cell Line Opposes Cancer Phenotype with a Concomitant Increase in p53 Phosphorylation. International Journal of Molecular Sciences. 2018; 19(7):2115. https://doi.org/10.3390/ijms19072115

Chicago/Turabian Style

Pesi, Rossana, Edoardo Petrotto, Laura Colombaioni, Simone Allegrini, Mercedes Garcia-Gil, Marcella Camici, Lars Petter Jordheim, and Maria Grazia Tozzi. 2018. "Cytosolic 5′-Nucleotidase II Silencing in a Human Lung Carcinoma Cell Line Opposes Cancer Phenotype with a Concomitant Increase in p53 Phosphorylation" International Journal of Molecular Sciences 19, no. 7: 2115. https://doi.org/10.3390/ijms19072115

APA Style

Pesi, R., Petrotto, E., Colombaioni, L., Allegrini, S., Garcia-Gil, M., Camici, M., Jordheim, L. P., & Tozzi, M. G. (2018). Cytosolic 5′-Nucleotidase II Silencing in a Human Lung Carcinoma Cell Line Opposes Cancer Phenotype with a Concomitant Increase in p53 Phosphorylation. International Journal of Molecular Sciences, 19(7), 2115. https://doi.org/10.3390/ijms19072115

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