Fig. 4

Glucose restriction sensitizes p53-proficient HCT116 cells to irinotecan. A p53 wild-type (HCT^wt) and isogenic p53 null (HCT^Δp53) HCT116 cells were exposed to 10 µM irinotecan (Iri). The abundance of indicated metabolites was assessed after 24 h by targeted mass spectrometric analysis (metabolomics) (refer to Fig. 3). Changes of individual metabolites are summarized for the HCT116 cell lines. Green/red color indicates a higher/lower abundance after irinotecan treatment, respectively. Black indicates no change after treatment. If not further specified, metabolites in both HCT^wt (wt) and HCT^Δp53 (Δp53) were altered in the same way. Abbreviations: ETC electron transport chain, PPP pentose phosphate pathway, ROS reactive oxygen species, GSH/GSSG reduced/oxidized glutathione, PEP phosphoenolpyruvate. C–E HCT^wt and isogenic HCT^Δp53 cells cultured in DMEM with high (4.5 g/l) or low (1 g/l) glucose were exposed to 10 µM Iri. The loss of mitochondrial membrane potential (loss of ΔΨ_M) and cell death was analyzed by flow cytometry after 24 h (B) and 48 h (D). The oxygen consumption of HCT^wt cells was assessed after 24 h (C) and 48 h (E) using a Clarke electrode. B, D The average of 4 individual experiments ± SEM. C, E The average of 2 individual experiments ± SEM. Statistics for this figure: *p < 0.05; **p < 0.01