Inhibition of tumor cell growth by interferon-gamma is mediated by two distinct mechanisms dependent upon oxygen tension: induction of tryptophan degradation and depletion of intracellular nicotinamide adenine dinucleotide

The Journal of Clinical Investigation
T M Aune, S L Pogue

Abstract

Growth of a variety of human tumor cell lines is inhibited by interferon-gamma (IFN-gamma) in vitro. This mechanism is not well understood. The present experiments identify two separate mechanisms which account for the growth inhibitory activity of IFN-gamma. Cell lines most sensitive to IFN-gamma (inhibited by 10-30 U/ml IFN-gamma in 3 d) were stimulated by IFN-gamma to oxidize tryptophan in media to kynurenine and completely eliminated tryptophan from the culture media after 48-72 h. Addition of L-tryptophan, but not other aromatic amino acids, other essential amino acids, or D-tryptophan, prevented inhibition of cell growth by IFN-gamma. The amount of IFN-gamma required to yield 50% inhibition of cell growth was directly related to the concentration of L-tryptophan in culture media and increased from approximately 3 to 600 U/ml as the concentration of tryptophan in the media was increased from 25 to 1,000 microM. By contrast, inhibition of growth of the cell lines, BT20 and HT29, was not prevented by addition of tryptophan. Inhibition by IFN-gamma (100-300 U/ml after 5-6 d) was, however, completely prevented by addition of two inhibitors of adenosine diphosphate-ribosyl transferase (ADP-RT), 3-aminobenzamide or nicotinamide....Continue Reading

References

Oct 19, 1976·Biochemistry·K W KohnC A Friedman
Oct 1, 1987·Journal of Interferon Research·E C BordenG I Byrne
Feb 1, 1985·The Journal of Clinical Investigation·S SetoD A Carson
Feb 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·Y OzakiD S Duch
Jan 1, 1985·Annual Review of Biochemistry·K Ueda, O Hayaishi
Apr 22, 1985·Journal of Immunological Methods·J De la Harpe, C F Nathan
May 1, 1971·Proceedings of the National Academy of Sciences of the United States of America·J M McCordI Fridovich
Jan 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·R YoshidaO Hayaishi
Feb 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·E R Pfefferkorn
Apr 29, 1983·Science·A Meister
Jun 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·G FiskumA L Lehninger

❮ Previous
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Citations

May 13, 2009·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Carlos E A BatistaDiane C Chugani
Jan 15, 2004·Trends in Molecular Medicine·David H Munn, Andrew L Mellor
Nov 12, 2003·The Journal of Allergy and Clinical Immunology·Dagmar von BubnoffThomas Bieber
Jul 10, 2003·Immunology and Cell Biology·John R Moffett, Ma Aryan Namboodiri
May 4, 1999·The Journal of Experimental Medicine·D H MunnA L Mellor
Jul 7, 2001·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·S CurreliD Zella
Feb 1, 1995·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·A NaldiniV Bocci
Sep 1, 1996·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·K V Konan, M W Taylor
Jul 1, 1997·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·B D Hissong, J M Carlin
Mar 24, 2000·Redox Report : Communications in Free Radical Research·S R Thomas, R Stocker
Dec 17, 2014·Immunological Reviews·Michelle H Nelson, Chrystal M Paulos
Aug 27, 2014·Frontiers in Immunology·Susanne V Schmidt, Joachim L Schultze
Aug 5, 2005·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Csaba JuhászHarry T Chugani
Jul 29, 2008·Current Opinion in Organ Transplantation·Gerald BrandacherDietmar Fuchs
Jul 18, 2015·Clinical Science·Amanda W S YeungShane R Thomas
May 9, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·S R ThomasR Stocker
Aug 5, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sophie AgauguéVincent Lotteau
Mar 20, 2020·Nutrition & Metabolism·Jian-Sheng Kang
Dec 31, 1997·The American Journal of Physiology·L P WenG D Rosen

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