Treatment of ME180 Cells with Interferon-γ Causes Apoptosis as a Result of Tryptophan Starvation

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Abstract
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-γ) treatment. The induction of this enzyme has been associated with the antiparasitic and cytotoxic activities of human IFN-γ. DNA analysis coupled to morphologic studies indicated that ME180 cells underwent apoptosis within 48 h of treatment with IFN-γ. 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-γ-treated cells and the induction of apoptosis by removing tryptophan from the medium in the absence of LFN-γ.