Fig. 1: ASNase treatment triggers elevated serine and glycine levels in tumor cells in vitro and in vivo. | Nature Communications

Fig. 1: ASNase treatment triggers elevated serine and glycine levels in tumor cells in vitro and in vivo.

From: Tumor metabolic adaptation induced by L-asparaginase reveals a vulnerability to PARP1/2 inhibitor in B-cell lymphomas

Fig. 1: ASNase treatment triggers elevated serine and glycine levels in tumor cells in vitro and in vivo.The alternative text for this image may have been generated using AI.

a Survival curves of mice bearing OxPhos-dependent Eμ-Myc #506 cell-derived B-cell lymphomas (BCL), treated with Vehicle or ASNase every 48 h till disease endpoint (Vehicle, n = 25 mice; ASNase, n = 26 mice, n = 3 independent experiments). b As in a with OxPhos-dependent Eµ-Myc #688 cells (n = 16 mice/group, n = 2 independent experiments). c Principal-component analysis (PCA) of 136 detected metabolites in BCL from C57BL/6 mice engrafted with Eµ-Myc #506 cells and treated with Vehicle or ASNase from day 7 until endpoint (n = 10 mice/group). d As in (c) using mice engrafted with Eµ-Myc #688 cells (based on 131 metabolites detected) (n = 12 mice/group). e Volcano plot highlighting significantly deregulated metabolites (Fold change (ASNase/Vehicle)>1.25 and raw P-value < 0.05) in Eµ-Myc #506 cell-derived BCL described in (c). (n = 10 mice/group). Nucleotide precursors in blue, proteinogenic amino acid in pink. f Venn diagram illustrating the number of statistically significant deregulated metabolites in ASNase-treated BCL highlighted in (e), S1e. g Overview of top statistically significant enriched KEGG metabolite sets from 19 commonly deregulated metabolites highlighted in (f) in ASNase-treated BCL. Relative abundance (peak area) of total intracellular serine (h) and glycine (i) in BCL presented in (c) and in (d) (from Eµ-Myc #506 cells, n = 10 mice/group; from Eµ-Myc #688 cells, n = 12 mice/group). j Percentage of dead Eμ-Myc #506 cells (DAPI+) cultivated for 24 h in Asn-free medium supplemented with (+) or without (−) Asn (0.37 mM) and ASNase (0.003 IU/ml) (n = 6 independent experiments). k Proliferation of Eµ-Myc (#506) cells cultivated as in (j). (n = 6 independent experiments). Relative abundance (peak area) of total intracellular serine (l) and glycine (m) in live Eµ-Myc (#506) cells cultivated for 24 h as in (j) (n = 4 biological and two technical replicates). Data are expressed as mean ± SD (h, i, j, l, m) or ± SEM (k). P-values are from log-rank test (a, b), non-parametric Wilcoxon rank-sum test (e), Fisher’s exact test followed by Bonferroni correction (g), t-test (h, i), one-way Anova followed by Tukey’s test (j, l, m) and indicated as **, p < 0.01; ***, p < 0.001; ****, p < 0.0001. For detailed individual P-value, please refer to the Source data table.

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