Elesclomol-Cu Induces Cuproptosis in Human Acute Myeloid Leu-kemia Cells
10.19746/j.cnki.issn1009-2137.2024.02.010
- VernacularTitle:伊利司莫-铜诱导急性髓系白血病细胞发生铜死亡
- Author:
Yan-Hua YU
1
;
Huan-Juan LI
;
Xin-Yi YANG
;
Ling-Yan YU
;
Xiang-Min TONG
Author Information
1. 浙江中医药大学第二临床医学院,浙江杭州 310053;浙江省人民医院(附属人民医院)临床医学研究所,杭州医学院,浙江杭州 310014
- Keywords:
acute myeloid leukemia;
elesclomol-Cu;
cuproptosis
- From:
Journal of Experimental Hematology
2024;32(2):389-394
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effects of elesclomol-Cu(ES-Cu)on the proliferation and cuproptosis of human acute myeloid leukemia(AML)cells.Methods:The effects of ES-Cu on the proliferation of AML cells and the AML cells pre-treated with ammonium tetrathiomolybdate(TTM)were examined by CCK-8 assay.The Calcein/PI kit was used to detected the changes in activity and cytotoxicity of AML cells induced by ES-Cu.Flow cytometry and Cytation3 fully automated cell imaging multifunctional detection system were used to analyze DCFH-DA fluorescence intensity,so as to determine the level of reactive oxygen species(ROS).The GSH and GSSG detection kits were used to measure the intracellular GSH content.Western blot was used to detected the expression of cuproptosis-related proteins ATP7B,FDX1,DLAT and DPYD.Results:ES-Cu inhibited the proliferation of Kasumi-1 and HL-60 cells in a concentration-dependent manner(rKasumi-1=-0.99,rHL-60=-0.98).As the concentration of ES-Cu increased,the level of intracellular ROS also increased(P＜0.01-0.001).TTM could significantly reverse the inhibitory effect of ES-Cu on cell proliferation and its promoting effect on ROS.With the increase of ES-Cu concentration,the content of GSH was decreased(r=-0.98),and Western blot showed that the protein expressions of ATP7B,FDX1,DLAT and DPYD were significantly reduced(P＜0.05).Conclusion:ES-Cu can induce cuproptosis in AML cells,which provides a new idea for the treatment of AML.
