Additional file 6: of Glutamine to proline conversion is associated with response to glutaminase inhibition in breast cancer

Figure showing the effect of CB-839 in MAS98.06 and MAS98.12 tumors. a) Average 13C NMR spectra (173.5-185.5 ppm and 75-13 ppm) for CB-839-treated and untreated MAS98.06 and MAS98.12 models receiving 13C-labeled glutamine. b) Quantified amounts of 13C-labeled metabolites in each experimental group: 13C glutamine ([5-13C] Gln), glutamate ([5-13C] Glu and [1-13C] Glu), alanine ([1-13C] Ala), lactate ([1-13C] Lac, proline ([5-13C] Pro), and glutamate to glutamine ratio ([5-13C] Glu/[5-13C] Gln) in the experimental groups. c) MAS98.06 tumors take up and store glutamine (Gln) in the tumors and use glutamine to produce proline (Pro), alanine (Ala), lactate (Lac), and glutamate (Glu) through one turn in TCA cycle as indicated by filled blue circles (Lac only borderline significant, gray circle). CB-839 causes an accumulation of Gln (arrow up) and reduced amounts of Pro, Ala, and Glu (arrows down) in the tumors (only [1-13C] Glu, which is created after one turn in TCA cycle, is reduced). MAS98.12 tumors use glutamine (Gln) to produce Glu, Lac, and Ala as indicated by filled pink circles (Ala only borderline significant, gray circle). CB-839 causes accumulation of Gln in MAS98.12 tumors, but does not significantly change the amount of any other 13C-enriched metabolites. d) Quantified amount of relevant metabolites from 1H spectra. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 (PPTX 339 kb)