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Updated: Aug 17, 2026
Synthesis and Characterization of an Aspirin-fumarate Prodrug that Inhibits NFκB Activity and Breast Cancer Stem Cells
Published on: January 18, 2017
Aspirin inhibits NF-kappaB activation in a glycolysis-depleted lung epithelial cell line
Eduardo Cuesta1, Jordi Boada, Jose C Perales
1Departament de Ciències Fisiològiques II, IDIBELL-Universitat de Barcelona, Feixa Llarga s/n, E-08907 L'Hospitalet de Llobregat, Spain.
Abstract:
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.
Insights
Aspirin complements cancer therapies targeting glycolysis by reducing resistance linked to nuclear factor kappa B (NF-kappaB) activity and oxidative stress. This adjuvant strategy enhances therapeutic outcomes in glycolysis-restricted cancer cells.
Area of Science:
- Biochemistry
- Oncology
- Pharmacology
Background:
- Glycolysis inhibition, specifically at the phosphofructo-1-kinase step, slows cancer cell growth.
- Overexpression of fructose-2,6-bisphosphatase is a potential antineoplastic strategy.
- Glycolysis restriction can lead to side effects like increased resistance to oxidants and TNF-alpha, and elevated NF-kappaB activity.
Purpose of the Study:
- To evaluate aspirin as an adjuvant therapy for cancer treatment involving glycolysis restriction via fructose-2,6-bisphosphatase overexpression.
- To assess the impact of aspirin on antioxidant defenses and NF-kappaB activity in both control and fructose-2,6-bisphosphatase-overexpressing cells.
Main Methods:
- Overexpression of fructose-2,6-bisphosphatase in cancer cells.
- Treatment with aspirin.
- Evaluation of antioxidant defenses.
- Assessment of nuclear factor kappa B (NF-kappaB) activity.
Main Results:
- Aspirin demonstrated an inhibitory effect on NF-kappaB activity.
- This aspirin-induced inhibition of NF-kappaB was more pronounced in cells with restricted glycolysis (fructose-2,6-bisphosphatase overexpressors) compared to control cells.
- Aspirin's effects on antioxidant defenses were also evaluated.
Conclusions:
- Aspirin is a suitable adjuvant to glycolysis restriction therapies.
- Aspirin can overcome treatment resistance associated with increased NF-kappaB activity and oxidative stress in glycolysis-restricted cancers.
- This combination therapy holds promise for improved antineoplastic outcomes.
