Antiproliferative activity of gamma-interferon combined with lipopolysaccharide on murine adenocarcinoma: dependence on an L-arginine metabolism with production of nitrite and citrulline.
Growth of the murine adenocarcinoma EMT6 was moderately inhibited by up to 32 units/ml of gamma-interferon (IFN-gamma). However, EMT6 growth was blocked by as low as 2 U/ml of IFN-gamma, when added with lipopolysaccharide. In the same time, the combination IFN-gamma + lipopolysaccharide induced synergistically the production of nitrite and citrulline by EMT6 cells. Synthesis of the two products was correlated with IFN-gamma concentrations. It required exogenous L-arginine and was inhibited by a methylated L-arginine derivative, NG-monomethyl-L-arginine. Inhibition was specific since urea synthesis was not reduced by NG-monomethyl-L-arginine. The L-arginine-dependent pathway was involved in EMT6 cytostasis mediated by IFN-gamma + lipopolysaccharide because cytostasis expression required L-arginine and was inhibited by NG-monomethyl-L-arginine.
Lepoivre
M
M
U. A. 1116, Institut de Biochimie, Université de Paris-Sud, Orsay, France.
Boudbid
H
H
Petit
J F
JF
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002956:Citrulline / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009573:Nitrites / Q000378:metabolism*; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured / Q000187:drug effects
D008070:Lipopolysaccharides; D009573:Nitrites; D011994:Recombinant Proteins; D002956:Citrulline; D007371:Interferon-gamma; D001120:Arginine