N-acetyl-L-cysteine protects endothelial cells but not L929 tumor cells from tumor necrosis factor-alpha-mediated cytotoxicity.
The effect of N-acetyl-L-cysteine on the cytotoxicity of tumor necrosis factor-alpha was investigated in cultured bovine pulmonary artery endothelial cells and L929 mouse tumor cells. In endothelial cells, a 72-h incubation with tumor necrosis factor-alpha (100 ng/ml) reduced the number of viable cells to 27% of control. Simultaneous incubation with N-acetyl-L-cysteine (0.5-5 mmol/l) protected endothelial cells from tumor necrosis factor-alpha-mediated cytotoxicity and increased viability in a concentration-dependent fashion to 69% of control. Under the same conditions, a 72-h incubation with tumor necrosis factor-alpha (100 ng/ml) reduced the number of viable L929 tumor cells to 31% of control. However, this cytotoxic response remained unaltered in the presence of N-acetyl-L-cysteine (0.5-5 mmol/l). Similar results were obtained when using a lower concentration of tumor necrosis factor-alpha (50 ng/ml). These findings demonstrate protection from tumor necrosis factor-alpha-mediated toxicity by N-acetyl-L-cysteine in endothelial cells but not in a tumor cell line. It is concluded that N-acetyl-L-cysteine might serve as a therapeutic agent to limit the vascular toxicity of tumor necrosis factor-alpha without affecting its antineoplastic activity.
Schröder
H
H
Stanford University School of Medicine, Division of Oncology, VAMC, Palo Alto, CA 94304.
Warren
S
S
Bargetzi
M J
MJ
Torti
S V
SV
Torti
F M
FM
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000633:toxicity*
D014409:Tumor Necrosis Factor-alpha; D000111:Acetylcysteine