Research Paper Volume 14, Issue 23 pp 9466—9483

Figure 10. Treatment with carvedilol differentially affects both glycolysis and oxygen consumption rates in MCF7 cells, in a concentration-dependent manner. Cells were seeded and treated with carvedilol, as described above. Briefly, cells were seeded at a density of fifteen thousand in a 96-well format. (A) Extracellular consumption rate (ECAR) was assessed by Seahorse metabolic flux analysis. A representative trace is shown in the top panel. Importantly, carvedilol treatment induced glycolysis by >3.5-fold at 25 μM, but showed dramatic inhibition of glycolysis at 50 μM. (B) Oxygen consumption rate (OCR) was measured by Seahorse metabolic flux analysis. A representative trace, in the top panel, shows progressive decreases in OCR in samples treated with carvedilol (25 and 50 μM), versus the vehicle alone control cells. The bar graph (lower panel) shows that carvedilol treatment significantly decreases the basal respiration, ATP production, maximal and spare respiration, as compared to the control cells. In summary, at 25 μM, carvedilol enhanced glycolysis, but inhibited mitochondrial oxygen consumption. In contrast, at 50 μM, carvedilol inhibited both glycolysis and mitochondrial oxygen consumption. In panels A and B, experiments were performed three times independently, with six repeats for each replicate. Bar graphs are shown as the mean ± SEM, t-test, two-tailed test. *p < 0.05, ***p < 0.001.