PMID- 21789245
OWN - NLM
STAT- MEDLINE
DCOM- 20111122
LR  - 20231105
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 6
IP  - 7
DP  - 2011
TI  - Energy metabolism in H460 lung cancer cells: effects of histone deacetylase 
      inhibitors.
PG  - e22264
LID - 10.1371/journal.pone.0022264 [doi]
AB  - BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 
      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. CONCLUSION: NaB and TSA induced an increase in 
      mitochondrial function and oxidative metabolism in H460 lung tumor cells 
      concomitant with a less proliferative cellular phenotype.
FAU - Amoedo, Nivea Dias
AU  - Amoedo ND
AD  - Instituto de Bioquimica Medica, Universidade Federal do Rio de Janeiro, Cidade 
      Universitaria, Rio de Janeiro, Brazil.
FAU - Rodrigues, Mariana Figueiredo
AU  - Rodrigues MF
FAU - Pezzuto, Paula
AU  - Pezzuto P
FAU - Galina, Antonio
AU  - Galina A
FAU - da Costa, Rodrigo Madeiro
AU  - da Costa RM
FAU - de Almeida, Fabio Ceneviva Lacerda
AU  - de Almeida FC
FAU - El-Bacha, Tatiana
AU  - El-Bacha T
FAU - Rumjanek, Franklin David
AU  - Rumjanek FD
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110718
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Butyrates)
RN  - 0 (Glucose Transporter Type 1)
RN  - 0 (Glucose Transporter Type 3)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Hydroxamic Acids)
RN  - 0 (Lactates)
RN  - 0 (SLC2A1 protein, human)
RN  - 0 (SLC2A3 protein, human)
RN  - 3X2S926L3Z (trichostatin A)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - EC 1.1.1.47 (Glucose 1-Dehydrogenase)
RN  - EC 1.3.99.1 (Succinate Dehydrogenase)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - EC 2.7.1.40 (Pyruvate Kinase)
SB  - IM
MH  - Butyrates/pharmacology
MH  - Cell Cycle/drug effects
MH  - Cell Differentiation/drug effects
MH  - Cell Line, Tumor
MH  - Cell Membrane Permeability/drug effects
MH  - Cell Proliferation/drug effects
MH  - Cell Respiration/drug effects
MH  - Cell Shape/drug effects
MH  - Energy Metabolism/*drug effects
MH  - Glucose 1-Dehydrogenase/metabolism
MH  - Glucose Transporter Type 1/metabolism
MH  - Glucose Transporter Type 3/metabolism
MH  - Glycolysis/drug effects
MH  - Hexokinase/metabolism
MH  - Histone Deacetylase Inhibitors/*pharmacology
MH  - Humans
MH  - Hydroxamic Acids/pharmacology
MH  - L-Lactate Dehydrogenase/metabolism
MH  - Lactates/metabolism
MH  - Lung Neoplasms/enzymology/*metabolism/pathology
MH  - Mitochondria/drug effects/metabolism
MH  - Protein Binding/drug effects
MH  - Pyruvate Kinase/metabolism
MH  - Succinate Dehydrogenase/metabolism
PMC - PMC3138778
EDAT- 2011/07/27 06:00
MHDA- 2011/12/13 00:00
CRDT- 2011/07/27 06:00
PHST- 2011/02/01 00:00 [received]
PHST- 2011/06/20 00:00 [accepted]
PHST- 2011/07/27 06:00 [entrez]
PHST- 2011/07/27 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
AID - PONE-D-11-02252 [pii]
AID - 10.1371/journal.pone.0022264 [doi]
PST - ppublish
SO  - PLoS One. 2011;6(7):e22264. doi: 10.1371/journal.pone.0022264. Epub 2011 Jul 18.