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Fig. 4 | Cancer & Metabolism

Fig. 4

From: Impaired anaplerosis is a major contributor to glycolysis inhibitor toxicity in glioma

Fig. 4

Synergistic anti-neoplastic effect of POMHEX and CB-839 in pyruvate free condition. a-d ENO1 homozygously deleted (D423; red, N=2), ENO1 isogenically rescued (D423 ENO1; blue, N=2) and ENO1 WT (LN319; grey, N=2) cells were seeded in 96 well plates. After 24 h, the cells were treated with serial dilutions of POMHEX alone a and b or in combination with a fixed 500 nM CB-839 in pyruvate-free and pyruvate-supplemented medium (Columns 1-2 vehicle control; 3-10 serial dilutions of POMHEX and constant 500 nM CB-839; 11-12 constant 500 nM CB-839) c and d. The cells were grown in pyruvate free a and c or 5 mM pyruvate supplemented medium b and d. Following 5 days of drug treatment, cells were fixed and crystal violet staining was performed to determine cell density in response to the drug treatment. Data are expressed relative to the untreated control. Note the substantial synergy between POMHEX and CB-839 which is accentuated in pyruvate-free condition c and partially reversed by pyruvate supplementation d. e Schematic showing the inhibition of glycolysis by POMHEX at the enolase step, and inhibition of glutaminolysis by CB-839, both converging to impede TCA cycle anaplerosis, at different steps of the cycle

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