Treatment of ME180 cells with interferon-gamma causes apoptosis as a result of tryptophan starvation.
Indoleamine 2'3 dioxygenase (INDO), the rate-limiting enzyme in the catabolism of the essential amino acid L-tryptophan, is induced in many cell lines following interferon gamma (IFN-gamma) treatment. The induction of this enzyme has been associated with the antiparasitic and cytotoxic activities of human IFN-gamma. DNA analysis coupled to morphologic studies indicated that ME180 cells underwent apoptosis within 48 h of treatment with IFN-gamma. We hypothesized that apoptosis results from L-tryptophan starvation following INDO induction. This was confirmed by the prevention of apoptosis on adding back tryptophan to IFN-gamma-treated cells and the induction of apoptosis by removing tryptophan from the medium in the absence of IFN-gamma.
Konan
K V
KV
Department of Biology, Indiana University, Bloomington, USA.
Taylor
M W
MW
D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D004790:Enzyme Induction; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009336:Necrosis; D014364:Tryptophan / Q000172:deficiency* / Q000494:pharmacology; D014366:Tryptophan Oxygenase / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D007371:Interferon-gamma; D014364:Tryptophan; D014366:Tryptophan Oxygenase