TABLE 1.
Effects of the inhibition of NAMPT by FK866 on the levels (ng/ml) of major isotope-labeled metabolites derived from [1,6-13C]glucose in A2780 cells
A2780 cells were grown in the presence of [1,6-13C]glucose, treated with FK866, and processed for the analysis of metabolites by LC-MS as described (“Experimental Procedures”). Only the major 13C-labeled metabolites are reported. S7P, sedoheptulose 7-phosphate; Gn6P, 6-phosphogluconate; R5P, ribose 5-phosphate, ribulose 5-phosphate, and xylulose 5-phosphate; G6P, glucose 6-phosphate; FBP, fructose 1,6-bisphosphate; G3P, glyceraldehyde 3-phosphate; PG, 2-phosphoglycerate and 3-phosphoglycerate; PEP, phosphoenolpyruvate. M2, 2 carbons of the metabolites were 13C-labeled. M1, 1 carbon of the metabolites was 13C-labeled.
| FK866 (nm) | Metabolite levelsa (ng/ml) |
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| S7P(M1) | S7P(M2) | Gn6P(M1) | Gn6P(M2) | R5P(M1) | R5P(M2) | G6P(M2) | FBP(M2) | G3P(M1) | PG(M1) | PEP(M1) | |
| 0.0 | 3.8 ± 0.8 | 9.4 ± 0.6 | 0.7 ± 0.2 | 6.5 ± 0.6 | 18 ± 1.4 | 5 ± 0.6 | 63 ± 8.4 | 213 ± 32 | 44.5 ± 7.5 | 141 ± 1.8 | 17.7 ± 1.1 |
| 0.33 | 3.8 ± 0.8 | 11 ± 1.7 | 0.6 ± 0.1 | 4.9 ± 1 | 17.2 ± 4.3 | 5 ± 1 | 66 ± 11.3 | 237 ± 43 | 50 ± 11.3 | 129 ± 2.8 | 13.9 ± 1.9 |
| 3.3 | 10.7 ± 0.1 | 95 ± 2.1 | 0.7 ± 0.1 | 5.6 ± 0.7 | 23 ± 1.1 | 12.6 ± 0.5 | 368 ± 13 | 1833 ± 184 | 336 ± 51 | 47 ± 7 | 3.1 ± 0.3 |
| 33 | 17.2 ± 0.7 | 162 ± 6.2 | 1.1 ± 0.1 | 7.6 ± 0.8 | 28 ± 4.2 | 15.3 ± 1.4 | 543 ± 35 | 2947 ± 114 | 571 ± 46 | 52 ± 0.2 | 3.3 ± 0.2 |
a Tumor metabolite levels (means ± S.E.).