Figure 3

Sensitivity of cells to metformin is dependent on the capacity to engage in aerobic glycolysis. (A-B) Total respiration is presented as fold change upon metformin treatment (0.5mM) from untreated conditions. (C-D) The mitochondrial coupling status represents coupled and uncoupled respiration as a fraction of total mitochondrial respiration, for both untreated and treated conditions. (E-F) Glucose consumption, (G-H) lactate production and (I-J) live cell counts of cells treated with metformin (5 mM) for either 24 or 48 hours are represented as a fold change from untreated conditions. (K) Mitochondrial respiration of MCF7 cells grown in glucose or galactose media in the presence of ddH₂0 (control) or metformin (0.5 mM) for 24 hours. Data are normalized to the respiration rate of MCF7 cells in the presence of glucose without metformin. (L) The fractions of mitochondrial respiration devoted to coupled and uncoupled respiration were calculated as in C-D. (M) Live cell counts for MCF7 cells cultured in galactose media with treatment of metformin (0.5 or 5.0 mM) for periods of 24, 48 and 72 hours, are represented as a fold change from untreated conditions. For (A-D), Data are presented as means ± SEM. n = 4, where *P <0.05, Student’s t- test. For (E-J,L,M), data are presented as means ± SEM. n = 3, # and *P <0.05, Student’s t- test, where * represents a significant change from untreated conditions and # represents a significant change between indicated cell lines. For (K), data are presented as means ± SEM. n = 3, # and *P <0.05, Student’s t- test, where * represents a significant change from the respiration rate of MCF7 cells in the presence of glucose without metformin, while # represents a significant change from the respiration rate of MCF7 cells in the presence of galactose without metformin.