Mechanisms of the induction of apoptosis in human hepatoma cells by tumour necrosis factor-alpha.
Tumour necrosis factor alpha (TNF-alpha) at 20 ng/ml induced apoptosis in human hepatoma cells in vitro. The effect of TNF-alpha-induced apoptosis was exacerbated by the hypoxanthine-xanthine oxidase (HX/XO) system and cycloheximide (CHX), but alleviated by superoxide dismutase (SOD), suggesting that TNF-alpha-induced apoptosis may be due to oxidative stress, and independent of protein synthesis. TNF-alpha elevated free Ca(2+)concentration, triggered lipid peroxidation and decreased the expression of bcl-2 protein. The findings suggest that TNF-alpha-induced apoptosis may be involved in stimulating Ca(2+)-dependent endonuclease activity and increasing membrane lipid peroxidation. Bcl-2 may play a pivotal role in serving as a Ca(2+)regulator or antioxidant, preventing lipid peroxidation in the process.
Li
J
J
Center Laboratory, Shandong Provincial Hospital, Jinan 250021, PR China.
Zheng
R
R
Li
J
J
Wang
Z
Z
D000165:Acridine Orange; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D003513:Cycloheximide / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D019271:Hypoxanthine / Q000378:metabolism; D015227:Lipid Peroxidation; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014969:Xanthine Oxidase / Q000378:metabolism
D011500:Protein Synthesis Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D019271:Hypoxanthine; D003513:Cycloheximide; D014969:Xanthine Oxidase; D000165:Acridine Orange; D002118:Calcium