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.