Figure 2.
Iron chelator VLX600 inhibited mitochondrial respiration and induced efficient cell death in MYCN-amplified neuroblastoma cells. (A,B) Dose-dependent sensitivity of MYCN-amplified IMR-32 and Sk-N-BE(2) neuroblastoma cells to VLX600. Left: bar chart, dose response from an individual experiment. Right: dose-response curve from three individual experiments. IC50 206 ± 9 nM in IMR-32 cells and IC50 326 ± 37 nM in Sk-N-BE(2). (C) Basal respiration level in IMR-32 cells treated with 200 nM or 400 nM VLX600. Oxygen Consumption Rate (OCR) was measured at indicated time points after VLX600 injection (6, 120 and 240 min). Final data are presented as percentage (%, normalized to values at time 0). (D) Maximal respiration level in IMR-32 cells treated with 200 nM or 400 nM VLX600 for 4 h. Oxygen Consumption Rate (OCR) was measured after FCCP injection. Final data are presented as percentage (%, normalized to values at time 0). (E) Basal respiration level in Sk-N-BE(2) cells treated with 200 nM or 400 nM VLX600. Oxygen Consumption Rate (OCR) was measured at indicated time points after VLX600 injection (6, 120 and 240 min). (F) Maximal respiration level in Sk-N-BE(2) cells treated with 200 nM or 400 nM VLX600 for 4 h. Oxygen Consumption Rate (OCR) was measured after FCCP injection. Final data are presented as percentage (%, normalized to values at time 0). (G) Glycolysis in IMR-32 cells treated with 200 nM or 400 nM VLX600. Extracellular acidification rate (ECAR) was measured at indicated time points after VLX600 injection (6, 120 and 240 min). (H) Glycolysis in Sk-N-BE(2) cells treated with 200 nM or 400 nM VLX600. Extracellular acidification rate (ECAR) was measured at the indicated time points after VLX600 injection (6, 120 and 240 min). Data are shown as mean ± SD, statistical analysis using two-tailed paired t-test. * p < 0.05, ** p < 0.01, *** p < 0.001 and **** p < 0.0001.
