Fig. 4: Targeting protein - PCNA interactions in haematological cells reduced central carbon metabolite pools.
From: PCNA regulates primary metabolism by scaffolding metabolic enzymes
A Glucose consumption (solid bars) and lactate secretion (dashed bars) per cell per 24 h given relative to untreated control (mean ± SD) in JJN3 cells (MM) treated with ATX-101 (orange), ATX-A (brown), or R11-peptide (green) (all 8 µM) (left) and ATX-101 treated MC/CAR (MM, 8 µM), RPMI 8226 (MM, 8 µM), NB4 (AML, 8 µM), HL60 (AML, 8 µM), HEK293 (embryonic kidney, 10 µM), and DU145 (prostate cancer, 8 µM) cells. (JJN3: *p < 0.05, **p < 0.01, ***p < 0.001, ANOVA, post hoc Tukey’s test, n ≥ 4, Other cell lines: *p < 0.05, **p < 0.01, ***p < 0.001, unpaired two-tailed student t-test, n ≥ 3). B Heat mapped log2 fold change of all quantified central carbon metabolites in ATX-101 treated cells given relative to untreated control; JJN3, RPMI 8226, MC/CAR, HL60, NB4, primary monocytes (all 8 µM ATX-101, 4 h), T24 (bladder cancer, 16 µM ATX-101, 24 h), DU145 (8 µM ATX-101, 4, 8, 24 h) and HEK293 (8 µM ATX-101, 4, 8, 24 h). C Heat mapped log2 fold change of central carbon metabolites in primary monocytes from three donors for LPS (10 ng/ml), ATX-101 (8 µM) (same data as monocytes in (B) and the combination treatment relative to untreated control. B, C Grey colour in heat map = not measured. Mean ± SD, n ≥ 3. Absolute Log2 fold changes are listed in Supplementary Table S2C. Experimental details are listed in Supplementary Table S1 and in [9]. Metabolite abbreviations and HMDB IDs are listed in Supplementary Table S2A. These results are previously published in BioRxiv [49].
