Tumor necrosis factor induces necrosis of human carcinoma xenografts in the presence of tricyclodecan-9-yl-xanthogenate and lauric acid.
Recombinant human tumor necrosis factor (rh TNF) when administered intravenously together with the phospholipase C inhibitor tricyclodecan-9-yl-xanthogenate (D609) and lauric acid (C12), leads to the partial regression of various human tumor transplants in athymic mice. Extensive necrosis occurred after a single intravenous infusion, with no detectable side effects. TNF-mediated cytotoxicity was found to be correlated with the depletion of energy in HeLa cells. The activity of rh TNF was enhanced by the absence of glucose, while it was reduced by addition of extraneous ATP. In the presence of rh TNF, D609, and C12, cellular energy metabolism was almost completely switched to glycolysis. Under these conditions the cytocidal activity of rh TNF on HeLa cells was amplified at least 60-fold.
Amtmann
E
E
Institute for Virus Research, German Cancer Research Center, Heidelberg.
Sauer
G
G
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D002460:Cell Line; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007850:Lauric Acids / Q000008:administration & dosage; D051379:Mice; D008819:Mice, Nude; D009336:Necrosis / Q000188:drug therapy / Q000473:pathology; D009368:Neoplasm Transplantation; D009636:Norbornanes; D011994:Recombinant Proteins / Q000627:therapeutic use; D013047:Specific Pathogen-Free Organisms; D013859:Thiocarbamates; D013871:Thiones / Q000008:administration & dosage; D014183:Transplantation, Heterologous; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D007850:Lauric Acids; D009636:Norbornanes; D011994:Recombinant Proteins; D013859:Thiocarbamates; D013871:Thiones; D014409:Tumor Necrosis Factor-alpha; C046498:tricyclodecane-9-yl-xanthogenate