Cytocidal mechanism of TNF: effects of lysosomal enzyme and hydroxyl radical inhibitors on cytotoxicity.
The participation of lysosomal enzymes, hydroxyl radicals, and mitochondrial respiration in the cytocidal effect of TNF on tumor cells was investigated. The cytotoxicity of TNF on L-M cells was clearly reduced by lysosomotropic agents, DMSO (hydroxyl radical scavenger), NDGA (lipoxygenase inhibitor), and sodium azide (mitochondrial respiration inhibitor). The results suggest that lysosomal enzyme and hydroxyl radicals play an important triggering role in the destruction of tumor cells by TNF, and that the process of destruction might require ATP.
Watanabe
N
N
Department of Internal Medicine, Sapporo Medical College, Japan.
Niitsu
Y
Y
Neda
H
H
Sone
H
H
Yamauchi
N
N
Maeda
M
M
Urushizaki
I
I
D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D002738:Chloroquine / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005609:Free Radicals; D006878:Hydroxides / Q000276:immunology*; D017665:Hydroxyl Radical; D007976:Leupeptins / Q000494:pharmacology; D009637:Masoprocol / Q000494:pharmacology; D008744:Methylamines / Q000494:pharmacology; D051379:Mice; D009113:Muramidase / Q000276:immunology* / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D005609:Free Radicals; D006878:Hydroxides; D007976:Leupeptins; D008744:Methylamines; D014409:Tumor Necrosis Factor-alpha; D000643:Ammonium Chloride; D017665:Hydroxyl Radical; D009637:Masoprocol; D002738:Chloroquine; C027451:methylamine; D009113:Muramidase; C032854:leupeptin; D004121:Dimethyl Sulfoxide