FIGURE 2.

Glycolytic inhibitors but not mitochondrial inhibitors induce an irreversible cytosolic Ca²⁺ overload in pancreatic cancer cells. Using fura-2 fluorescence imaging, [Ca²⁺]_i concentration was measured in PANC1 or MIA PaCa cells. A–D, representative traces show the effect of various metabolic inhibitors on [Ca²⁺]_i in PANC1 cells. Cells were treated for 30 min with either mitochondrial inhibitors (10 μm OM (A); 4 μm CCCP (C)) or glycolytic inhibitors (500 μm BrPy (B); 2 mm IAA (D)) followed by stimulation with the purinergic agonist, ATP (100 μm) to test for cell viability. Similar qualitative results were obtained for MIA PaCa-2 cells. Responses were quantified by measuring the AUC (E) for the 30-min treatment with drug and maximum change in [Ca²⁺]_i (F). Recovery from metabolic inhibitor treatment was assessed by measuring the % cells that subsequently responded to ATP (G). *, p < 0.05; **, p < 0.01; ***, p < 0.001 (E and F, unpaired Student's t test; G, Mann-Whitney U test) compared with control.