FIGURE 4 from LNS8801 inhibits Acute Myeloid Leukemia by Inducing the Production of Reactive Oxygen Species and Activating the Endoplasmic Reticulum Stress Pathway

Caspase cleavage mediates LNS8801-induced death. A, Annexin V+ flow cytometry analysis of human AML cell lines treated with 250 nmol/L LNS8801 for 72 hours. Three replicates were used per condition. B, Western blot analysis of AML cells treated with 250 nmol/L LNS8801 for 24 hours. Western blot quantification was done by normalizing bands to actin bands. Annexin V+ flow cytometry analysis of U937 (C) and MOLM14 (D) cells treated with LNS8801 and specific caspase inhibitors. A total of 250 nmol/L LNS8801, 10 μmol/L QVD-OPH (QVD), 50 μmol/L (U937), and 20 μmol/L (MOLM14) for Z-IETD-FMK (IETD), and 10 μmol/L Z-LEHD-FMK (LEHD) were used. L+Q indicates LNS8801 and QVD-OPH, L+I indicates LNS8801+Z-IETD-FMK, and L+L indicates LNS8801 and Z-LEHD-FMK. Three replicates were used per condition. Statistical analysis was done via pairwise t tests for A and one-way ANOVA with multiple comparisons was used for C and D (*, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.001; ****, P ≤ 0.0001).