Fig. 6.

Effect of desipramine on downstream signaling pathways of p53 activated by platinum drugs. a Effect on platinum-drug-induced mitochondrial damage. HCT116 cells were cultured with 50 μmol/L BBR3464, 10 μmol/L c-DDP, or 30 μmol/L oxaliplatin in the absence or presence of 40 μmol/L desipramine for 72 h. Reduction in mitochondrial membrane potential was assessed by staining with 3,3′-dihexyloxacarbocyanine iodide as described in “Materials and methods.” b Effect of desipramine on platinum-drug-induced caspase activation. HCT116 cells were cultured as in a. Cells were stained for active caspase 3/caspase 7 as described in “Materials and methods.” The data shown are the percentage of the population displaying active caspase 3/caspase 7. Each point represents the average (±SEM) of three independent experiments. c The effect of desipramine on poly(ADP ribose) polymerase (PARP) expression in platinum-drug-treated samples. HCT116 cells were precultured for 1 h with 40 μmol/L desipramine before the addition of 10 μmol/L platinum drugs for 24 h. The graph shows averages and standard deviations from three measurements of PARP expression normalized to actin loading control. Asterisks p < 0.05 when comparing cells treated with and without desipramine, by Student’s t test