Fig. 3: Dietary intervention causes substrate depletion to enhance polyamine biosynthesis inhibition by DFMO.
From: Reprogramming neuroblastoma by diet-enhanced polyamine depletion
a, Schematic of arginine, proline and glutamine metabolism and its direct link to polyamines via ornithine. GSAL, glutamate-γ-semialdehyde; P5C, pyrroline-5-carboxylate. b, Differential serum metabolite levels comparing ProArg-free diet with CD. Blue dots highlight metabolites that are significantly depleted (FDR < 0.05) and the rose dot indicates a metabolite that was upregulated compared with CD. CD: n = 8; ProArg-free: n = 7. c, Serum arginine, proline, glutamine and ornithine across groups. Statistical comparisons to CD. Data are mean ± s.e.m. CD: n = 8; CD + DMFO: n = 10; ProArg-free: n = 7; ProArg-free + DFMO: n = 7. d, Tumour arginine, proline, glutamine and ornithine levels reveal dysregulation of arginine and proline metabolism with combined ProArg-free diet plus DFMO treatment. Average age at end point is eight weeks. Statistical comparisons to CD. Data are mean ± s.e.m. CD: n = 5; CD + DMFO: n = 5; ProArg-free: n = 8; ProArg-free + DFMO: n = 4. e, A ProArg-free diet enhances polyamine depletion in tumour tissue induced by DFMO in prolonged treatment. Average age at end point is 12 weeks. Statistical comparisons to CD. Insets, magnified graphs highlight the additional difference in polyamine levels induced by ProArg-free diet over DFMO only. Data are mean ± s.e.m. CD: n = 5; CD + DMFO: n = 5; ProArg-free: n = 6; ProArg-free + DFMO: n = 4. Two-tailed t-test. n denotes the number of mice measured by metabolomics.
