Cytotoxic effect of cytokines on murine colon carcinoma cells involves TNF-mediated apoptosis.
We have studied the cytotoxic effect of TNF-alpha on C-26 murine colon carcinoma cells in vitro. Treatment with TNF-alpha alone did not result in any demonstrable cytotoxicity. However, when combined with IFN-gamma, the cytotoxic effect of TNF-alpha was enhanced in a dose-dependent manner. An agonistic TNF-R1 specific antibody and recombinant human TNF-alpha both exerted a cytotoxic effect when combined with IFN-gamma, suggesting that the cytotoxicity was mediated through the TNF-R1. The cytotoxicity was associated with production of nitric oxide without any direct involvement in the cytotoxic effect. At the ultrastructural level, treated cells displayed a typical apoptotic morphology which was not accompanied by internucleosomal cleavage of DNA as shown by conventional electrophoresis.
Sveinbjørnsson
B
B
Institute of Medical Biology, University of Tromsø, Norway. baldur@fagmed.uit.no
Rushfeldt
C
C
Olsen
R
R
Smedsrød
B
B
Seljelid
R
R
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000473:pathology* / Q000648:ultrastructure; D007371:Interferon-gamma / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma