Extended Data Fig. 5: DON treatment affects polar metabolite pools. | Nature Cancer

Extended Data Fig. 5: DON treatment affects polar metabolite pools.

From: Glutamine mimicry suppresses tumor progression through asparagine metabolism in pancreatic ductal adenocarcinoma

Extended Data Fig. 5: DON treatment affects polar metabolite pools.The alternative text for this image may have been generated using AI.

(a) Quantification of intracellular asparagine (Asn) levels in KPC cells treated with or without 10 μM DON and supplemented with or without 0.1 mM Asn for 24 h. Data are presented relative to vehicle control (Ctrl). Data are presented as mean ± SEM of at least n = 4 samples. Ctrl vs Asn, P = 0.0043. Ctrl vs DON, P < 0.0001. Asn vs DON+Asn, P = 0.0078. DON vs DON+Asn, P = 0.0074. (b) Quantification of intracellular aspartate (Asp) levels in PaTu 8988 T cells treated with or without DON at the indicated concentrations for 24 h. Data are presented relative to the 0 μM DON condition. Data are presented as mean ± SEM of n = 3 samples. 0 vs 2.5 μM, P = 0.1163. 2.5 μM vs 5 μM, P = 0.0011. 5 μM vs 10 μM, P = 0.0008. For all other statistical comparisons, P < 0.0001. (c–e) Quantification of intracellular levels of the indicated metabolites in KPC (c), 779E (d) or PaTu 8988 T (e) cells treated with vehicle control (Ctrl) or DON (10 μM, 10 μM, and 1 mM, respectively) for 24 h. Data are presented relative to Ctrl. Data are presented as mean ± SEM of n = 5 samples (c, d) and n = 3 samples (e). KPC cells: Glu, P = 0.0006. 779E cells: Succinate, P = 0.0003. PaTu 8988 T cells: Citrate, P = 0.0032. a-Ketoglutarate, P = 0.0009. Succinate, P = 0.0046. Fumarate, P = 0.0074. Malate, P = 0.013. For all other statistical comparisons, P < 0.0001. (f) Quantification of intracellular levels of the indicated metabolites in KPC cells treated with vehicle control (Ctrl), 10 μM DON and 10 μM DON supplemented with 0.1 mM Asn for 24 h. Data are presented relative to untreated control. Data are presented as mean ± SEM of at least n = 4 samples. Glu: Ctrl vs DON, P = 0.0018. DON vs DON+Asn, P = 0.0102. Citrate: Ctrl vs DON, P = 0.0060. DON vs DON+Asn, P = 0.0621. α-Ketoglutarate: Ctrl vs DON, P = 0.0029. DON vs DON+Asn, P = 0.0012. Succinate: Ctrl vs DON, P = 0.0166. DON vs DON+Asn, P = 0.4256. Fumarate: Ctrl vs DON, P = 0.0129. DON vs DON+Asn, P < 0.0001. Malate: Ctrl vs DON, P = 0.0024. DON vs DON+Asn, P = 0.1399. Statistical significance was calculated using unpaired two-tailed Student’s t test (a, c-f) or one-way ANOVA followed by Dunnet’s multiple comparisons test (b). *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, ns=not significant.

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