Aspirin inhibits NF-kappaB activation in a glycolysis-depleted lung epithelial cell line.
Inhibition of glycolysis at the phosphofructo-1-kinase step slows cell growth. For this reason, overexpression of fructose-2,6-bisphosphatase is a potential target for antineoplasic treatments. However, therapeutic objectives may be compromised by side effects of glycolysis restriction, including enhanced resistance to oxidants and tumor necrosis factor-alpha (TNF-alpha), as well as increased activity of the nuclear factor kappa B (NF-kappaB). In this study we evaluated aspirin as an adjuvant drug for glycolysis restriction by overexpression of fructose-2,6-bisphosphatase. The effect of aspirin on antioxidant defences and NF-kappaB activity were evaluated both in control cells and in fructose-2,6-bisphosphatase-overexpressing cells. Interestingly, aspirin-induced inhibition of NF-kappaB activity was greater in transfectants with restricted glycolysis than in control cells. Our results indicate that aspirin is a suitable complement to therapy based on glycolysis restriction to overcome resistance associated with increased NF-kappaB activity and oxidative stress.
Cuesta
Eduardo
E
Departament de Ciències Fisiològiques II, IDIBELL-Universitat de Barcelona, Feixa Llarga s/n, E-08907 L'Hospitalet de Llobregat, Spain.
Boada
Jordi
J
Perales
Jose C
JC
Roig
Teresa
T
Bermudez
Jordi
J
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001241:Aspirin / Q000494:pharmacology*; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006019:Glycolysis / Q000502:physiology*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000166:cytology; D016328:NF-kappa B / Q000378:metabolism*; D025481:Phosphofructokinase-2 / Q000235:genetics / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016328:NF-kappa B; D011993:Recombinant Fusion Proteins; D005979:Glutathione Peroxidase; D008156:Luciferases; D025481:Phosphofructokinase-2; D005978:Glutathione; D001241:Aspirin; D019803:Glutathione Disulfide