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

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posted on 2023-08-18, 14:20 authored by Inyoung Lee, Miriam Doepner, Jillian Weissenrieder, Ariana D. Majer, Sophia Mercado, Angela Estell, Christopher A. Natale, Pamela J. Sung, J. Kevin Foskett, Martin P. Carroll, Todd W. Ridky

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).


HHS | NIH | National Cancer Institute (NCI)



Previous work demonstrated that LNS8801 inhibits cancer via GPER activation, especially in solid tumors. Here we show that LNS8801 inhibits AML via GPER-independent mechanisms that include ROS induction and ER activation.