Figure 6.

Cells expressing mutant IDH1 are sensitive to pharmacologic inhibition of mitochondrial oxidative metabolism. A, doubling times of HCT116 cells cultured in normoxia or hypoxia (2% oxygen) for 72 hours. B, growth curves for HCT116 parental and IDH1-mutant xenografts. C, Western blot showing HIF1α expression in HCT116 parental and HCT116 IDH1 R132H/+ 2H1 cells grown in normoxia in cell culture (last two lanes) or as xenografts. D, ATP-linked oxygen consumption for the indicated cell lines grown in normoxia. E, ATP-linked oxygen consumption for the indicated cell lines grown in hypoxia (3% O₂). F, growth charts from cells cultured as indicated. Images were acquired every 12 hours to measure confluency. Change in growth relative to DMSO treatment (ΔX%) was calculated using a generalized logistics growth model for batch culture and represents the change in the specific growth rate relative to the DMSO treatment for the indicated cell line. G, heatmap displaying IC₅₀ values to four inhibitors of mitochondrial metabolism for more than 500 cancer cell lines; HT-1080 and SW1353 cells are indicated. H, growth of HT-1080 and SW1353 cells under the indicated concentration of phenformin for 48 hours.