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RESEARCH PRODUCT
Regulation of tumour cell sensitivity to TNF-induced oxidative stress and cytotoxicity: Role of glutathione
José A. PellicerElena ObradorJosé M. EstrelaJuan MompoMiguel AsensiJosé Bonet Navarrosubject
Programmed cell deathCell SurvivalClinical BiochemistryMitochondrionPharmacologyBiologymedicine.disease_causeBiochemistryMicechemistry.chemical_compoundSuperoxidesmedicineAnimalsHumansCarcinoma Ehrlich TumorGlutathione DisulfideTumor Necrosis Factor-alphaGeneral MedicineGlutathioneGlutathioneRecombinant ProteinsOxidative StresschemistryBiochemistryCancer cellMolecular MedicineGlutathione disulfideTumor necrosis factor alphaOxidative stressIntracellulardescription
Glutathione (GSH) and the rate of cellular proliferation determine tumour cell sensitivity to tumour necrosis factor (TNF). Buthionine sulphoximine (BSO), a selective inhibitor of GSH synthesis, inhibits tumour growth and increases recombinant human TNF (rhTNF)-alpha cytoxicity in vitro. Administration of sublethal doses of rhTNF-alpha to Ehrlich ascites-tumour (EAT)-bearing mice induces oxidative stress (as measured by increases in intracellular peroxide levels, O2.- generation and mitochondrial GSSG). ATP-induced selective GSH depletion, when combined with rhTNF-alpha administration, affords a 61% inhibition of tumour growth and results in a significant extent of host survival. Administration of N-acetylcysteine (NAC) or GSH ester abolishes the rhTNF-alpha and ATP-induced effects on tumour growth by maintaining high GSH levels in the cancer cells. TNF-induced mitochondria GSH depletion appears critical in the cascade of events that lead to cell death.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 1998-08-12 | BioFactors |