PMID- 18264981
OWN - NLM
STAT- MEDLINE
DCOM- 20080604
LR  - 20131121
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Linking)
VI  - 216
IP  - 1
DP  - 2008 Jul
TI  - Energy metabolism transition in multi-cellular human tumor spheroids.
PG  - 189-97
LID - 10.1002/jcp.21392 [doi]
AB  - It is thought that glycolysis is the predominant energy pathway in cancer, 
      particularly in solid and poorly vascularized tumors where hypoxic regions 
      develop. To evaluate whether glycolysis does effectively predominate for ATP 
      supply and to identify the underlying biochemical mechanisms, the glycolytic and 
      oxidative phosphorylation (OxPhos) fluxes, ATP/ADP ratio, phosphorylation 
      potential, and expression and activity of relevant energy metabolism enzymes were 
      determined in multi-cellular tumor spheroids, as a model of human solid tumors. 
      In HeLa and Hek293 young-spheroids, the OxPhos flux and cytochrome c oxidase 
      protein content and activity were similar to those observed in monolayer cultured 
      cells, whereas the glycolytic flux increased two- to fourfold; the contribution 
      of OxPhos to ATP supply was 60%. In contrast, in old-spheroids, OxPhos, ATP 
      content, ATP/ADP ratio, and phosphorylation potential diminished 50-70%, as well 
      as the activity (88%) and content (3 times) of cytochrome c oxidase. Glycolysis 
      and hexokinase increased significantly (both, 4 times); consequently glycolysis 
      was the predominant pathway for ATP supply (80%). These changes were associated 
      with an increase (3.3 times) in the HIF-1alpha content. After chronic exposure, 
      both oxidative and glycolytic inhibitors blocked spheroid growth, although the 
      glycolytic inhibitors, 2-deoxyglucose and gossypol (IC(50) of 15-17 nM), were 
      more potent than the mitochondrial inhibitors, casiopeina II-gly, laherradurin, 
      and rhodamine 123 (IC(50) > 100 nM). These results suggest that glycolysis and 
      OxPhos might be considered as metabolic targets to diminish cellular 
      proliferation in poorly vascularized, hypoxic solid tumors.
CI  - (c) 2008 Wiley-Liss, Inc.
FAU - Rodriguez-Enriquez, Sara
AU  - Rodriguez-Enriquez S
AD  - Departamento de Bioquimica, Instituto Nacional de Cardiologia, Mexico, Mexico. 
      saren960104@hotmail.com
FAU - Gallardo-Perez, Juan Carlos
AU  - Gallardo-Perez JC
FAU - Aviles-Salas, Alejandro
AU  - Aviles-Salas A
FAU - Marin-Hernandez, Alvaro
AU  - Marin-Hernandez A
FAU - Carreno-Fuentes, Liliana
AU  - Carreno-Fuentes L
FAU - Maldonado-Lagunas, Vilma
AU  - Maldonado-Lagunas V
FAU - Moreno-Sanchez, Rafael
AU  - Moreno-Sanchez R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Fluorescent Dyes)
RN  - 0 (Lactones)
RN  - 0 (Organometallic Compounds)
RN  - 0 (casiopeina II-glycine)
RN  - 0 (laherradurin)
RN  - 1N3CZ14C5O (Rhodamine 123)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - 9G2MP84A8W (Deoxyglucose)
RN  - KAV15B369O (Gossypol)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Cell Line, Tumor
MH  - Deoxyglucose/metabolism
MH  - *Energy Metabolism
MH  - Fluorescent Dyes/metabolism
MH  - Glycolysis/physiology
MH  - Gossypol/metabolism
MH  - Humans
MH  - Lactones/metabolism
MH  - *Neoplasms/metabolism/pathology
MH  - Organometallic Compounds/metabolism
MH  - Oxidative Phosphorylation
MH  - Oxygen/metabolism
MH  - Rhodamine 123
MH  - *Spheroids, Cellular
EDAT- 2008/02/12 09:00
MHDA- 2008/06/05 09:00
CRDT- 2008/02/12 09:00
PHST- 2008/02/12 09:00 [pubmed]
PHST- 2008/06/05 09:00 [medline]
PHST- 2008/02/12 09:00 [entrez]
AID - 10.1002/jcp.21392 [doi]
PST - ppublish
SO  - J Cell Physiol. 2008 Jul;216(1):189-97. doi: 10.1002/jcp.21392.