Tumour cell killing by tumour necrosis factor: inhibition by anaerobic conditions, free-radical scavengers and inhibitors of arachidonate metabolism.

Abstract

Previous work on the mechanism of tumour-cell killing by the macrophage product tumour necrosis factor (TNF) is consistent with a free radical-induced process. In this study, free-radical involvement was sought by (i) investigating the effects on TNF cytolysis of anaerobic conditions, free-radical scavengers and inhibitors of two potential pathways of free-radical generation (oxidative phosphorylation and arachidonate metabolism) and (ii) looking for increased malonyldialdehyde (MDA) production in TNF-treated cells (MDA is a free radical-induced lipid peroxidation product). Although TNF cytolysis of L929 cells was inhibited by anaerobic conditions, only limited effects were seen with free-radical scavengers. Suppression of arachidonate metabolism by steroids effectively inhibited TNF cytolysis but the mitochondrial poison rotenone did not. There was a marked, but late, increase in MDA production in TNF-treated cells. Overall, these results indicate that if free radicals are involved it is at a late stage in the cytolytic process. However the most striking observation in this study is that arachidonate metabolism is an essential link in the cytolytic process.

• Authors: N Matthews, M L Neale, S K Jackson, J M Stark
• Journal: Immunology (Immunology) Vol. 62 Issue 1 Pg. 153-5 (Sep 1987) ISSN: 0019-2805 [Print] England
• PMID: 3653925 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Arachidonic Acids
• Free Radicals
• Tumor Necrosis Factor-alpha
• Oxygen

Topics

• Animals
• Arachidonic Acids (metabolism)
• Cell Survival (drug effects)
• Free Radicals
• Mice
• Neoplasms, Experimental (metabolism, pathology)
• Oxygen
• Tumor Cells, Cultured
• Tumor Necrosis Factor-alpha (pharmacology)