Energy metabolism in H460 lung cancer cells: effects of histone deacetylase inhibitors.

<h4>Background</h4>Tumor cells are characterized by accelerated growth usually accompanied by up-regulated pathways that ultimately increase the rate of ATP production. These cells can suffer metabolic reprogramming, resulting in distinct bioenergetic phenotypes, generally enhancing glyc...

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Autores principales:	Nívea Dias Amoêdo, Mariana Figueiredo Rodrigues, Paula Pezzuto, Antonio Galina, Rodrigo Madeiro da Costa, Fábio Ceneviva Lacerda de Almeida, Tatiana El-Bacha, Franklin David Rumjanek
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a4e7cc3383a44c499d8bda56dfaf5965
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spelling	oai:doaj.org-article:a4e7cc3383a44c499d8bda56dfaf59652021-11-18T06:50:05ZEnergy metabolism in H460 lung cancer cells: effects of histone deacetylase inhibitors.1932-620310.1371/journal.pone.0022264https://doaj.org/article/a4e7cc3383a44c499d8bda56dfaf59652011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21789245/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Tumor cells are characterized by accelerated growth usually accompanied by up-regulated pathways that ultimately increase the rate of ATP production. These cells can suffer metabolic reprogramming, resulting in distinct bioenergetic phenotypes, generally enhancing glycolysis channeled to lactate production. In the present work we showed metabolic reprogramming by means of inhibitors of histone deacetylase (HDACis), sodium butyrate and trichostatin. This treatment was able to shift energy metabolism by activating mitochondrial systems such as the respiratory chain and oxidative phosphorylation that were largely repressed in the untreated controls.<h4>Methodology/principal findings</h4>Various cellular and biochemical parameters were evaluated in lung cancer H460 cells treated with the histone deacetylase inhibitors (HDACis), sodium butyrate (NaB) and trichostatin A (TSA). NaB and TSA reduced glycolytic flux, assayed by lactate release by H460 cells in a concentration dependent manner. NaB inhibited the expression of glucose transporter type 1 (GLUT 1), but substantially increased mitochondria bound hexokinase (HK) activity. NaB induced increase in HK activity was associated to isoform HK I and was accompanied by 1.5 fold increase in HK I mRNA expression and cognate protein biosynthesis. Lactate dehydrogenase (LDH) and pyruvate kinase (PYK) activities were unchanged by HDACis suggesting that the increase in the HK activity was not coupled to glycolytic flux. High resolution respirometry of H460 cells revealed NaB-dependent increased rates of oxygen consumption coupled to ATP synthesis. Metabolomic analysis showed that NaB altered the glycolytic metabolite profile of intact H460 cells. Concomitantly we detected an activation of the pentose phosphate pathway (PPP). The high O(2) consumption in NaB-treated cells was shown to be unrelated to mitochondrial biogenesis since citrate synthase (CS) activity and the amount of mitochondrial DNA remained unchanged.<h4>Conclusion</h4>NaB and TSA induced an increase in mitochondrial function and oxidative metabolism in H460 lung tumor cells concomitant with a less proliferative cellular phenotype.Nívea Dias AmoêdoMariana Figueiredo RodriguesPaula PezzutoAntonio GalinaRodrigo Madeiro da CostaFábio Ceneviva Lacerda de AlmeidaTatiana El-BachaFranklin David RumjanekPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 7, p e22264 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nívea Dias Amoêdo Mariana Figueiredo Rodrigues Paula Pezzuto Antonio Galina Rodrigo Madeiro da Costa Fábio Ceneviva Lacerda de Almeida Tatiana El-Bacha Franklin David Rumjanek Energy metabolism in H460 lung cancer cells: effects of histone deacetylase inhibitors.
description	<h4>Background</h4>Tumor cells are characterized by accelerated growth usually accompanied by up-regulated pathways that ultimately increase the rate of ATP production. These cells can suffer metabolic reprogramming, resulting in distinct bioenergetic phenotypes, generally enhancing glycolysis channeled to lactate production. In the present work we showed metabolic reprogramming by means of inhibitors of histone deacetylase (HDACis), sodium butyrate and trichostatin. This treatment was able to shift energy metabolism by activating mitochondrial systems such as the respiratory chain and oxidative phosphorylation that were largely repressed in the untreated controls.<h4>Methodology/principal findings</h4>Various cellular and biochemical parameters were evaluated in lung cancer H460 cells treated with the histone deacetylase inhibitors (HDACis), sodium butyrate (NaB) and trichostatin A (TSA). NaB and TSA reduced glycolytic flux, assayed by lactate release by H460 cells in a concentration dependent manner. NaB inhibited the expression of glucose transporter type 1 (GLUT 1), but substantially increased mitochondria bound hexokinase (HK) activity. NaB induced increase in HK activity was associated to isoform HK I and was accompanied by 1.5 fold increase in HK I mRNA expression and cognate protein biosynthesis. Lactate dehydrogenase (LDH) and pyruvate kinase (PYK) activities were unchanged by HDACis suggesting that the increase in the HK activity was not coupled to glycolytic flux. High resolution respirometry of H460 cells revealed NaB-dependent increased rates of oxygen consumption coupled to ATP synthesis. Metabolomic analysis showed that NaB altered the glycolytic metabolite profile of intact H460 cells. Concomitantly we detected an activation of the pentose phosphate pathway (PPP). The high O(2) consumption in NaB-treated cells was shown to be unrelated to mitochondrial biogenesis since citrate synthase (CS) activity and the amount of mitochondrial DNA remained unchanged.<h4>Conclusion</h4>NaB and TSA induced an increase in mitochondrial function and oxidative metabolism in H460 lung tumor cells concomitant with a less proliferative cellular phenotype.
format	article
author	Nívea Dias Amoêdo Mariana Figueiredo Rodrigues Paula Pezzuto Antonio Galina Rodrigo Madeiro da Costa Fábio Ceneviva Lacerda de Almeida Tatiana El-Bacha Franklin David Rumjanek
author_facet	Nívea Dias Amoêdo Mariana Figueiredo Rodrigues Paula Pezzuto Antonio Galina Rodrigo Madeiro da Costa Fábio Ceneviva Lacerda de Almeida Tatiana El-Bacha Franklin David Rumjanek
author_sort	Nívea Dias Amoêdo
title	Energy metabolism in H460 lung cancer cells: effects of histone deacetylase inhibitors.
title_short	Energy metabolism in H460 lung cancer cells: effects of histone deacetylase inhibitors.
title_full	Energy metabolism in H460 lung cancer cells: effects of histone deacetylase inhibitors.
title_fullStr	Energy metabolism in H460 lung cancer cells: effects of histone deacetylase inhibitors.
title_full_unstemmed	Energy metabolism in H460 lung cancer cells: effects of histone deacetylase inhibitors.
title_sort	energy metabolism in h460 lung cancer cells: effects of histone deacetylase inhibitors.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/a4e7cc3383a44c499d8bda56dfaf5965
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Energy metabolism in H460 lung cancer cells: effects of histone deacetylase inhibitors.

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