Dihydroartemisinin Induces Autophagic Cell Death in Acute Myeloid Leukemia Cells through Oxidative Stress.
10.19746/j.cnki.issn.1009-2137.2022.04.006
- Author:
Wei PAN
1
;
Yan SHEN
2
;
Bo LUO
3
;
Yu CAO
4
Author Information
1. Graduate School, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China; Department of Clinical Laboratory, Haiyan People's Hospital, Jiaxing 314000, Zhejiang Province, China.
2. Clinical Laboratory Center, Zhejiang Provincial People's Hospital, Hangzhou 310014, Zhejiang Province, China.
3. School of Laboratory Medicine, Zunyi Medical University, Zunyi 563000, Guizhou Province, China.
4. School of Laboratory Medicine, Zunyi Medical University, Zunyi 563000, Guizhou Province, China E-mail: 398223279@qq.com.
- Publication Type:Journal Article
- Keywords:
acute myeloid leukemia;
autophagy;
dihydroartemisinin;
oxidative stress
- MeSH:
Apoptosis;
Artemisinins/pharmacology*;
Autophagic Cell Death;
Autophagy;
Humans;
Leukemia, Myeloid, Acute;
Oxidative Stress
- From:
Journal of Experimental Hematology
2022;30(4):1011-1017
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the potential value and its mechanism of dihydroartemisinin (DHA) in the treatment of acute myeloid leukemia (AML).
METHODS:The effect of DHA on the viability of AML cells was detected by CCK-8 assay. The effect of DHA on intracellular oxidation-reduction state was detected by fluorescence probe staining and flow cytometry. Western blot, adenovirus transfection, and laser confocal analysis were used to analyze the effect of DHA on autophagy. The small molecule inhibitors were used to further elucidate the possible mechanism of DHA-induced AML cell death.
RESULTS:DHA could inhibit the viability of HL-60 and Kasumi-1 cell lines, and significantly increase the level of intracellular oxidative stress. When treated with 10 μmol/L DHA, reactive oxygen species (ROS) in HL-60 cells and Kasumi-1 cells was increased to 2.6 times and 2.0 times, respectively. In addition, the expression of autophagy-related proteins were up-regulated in DHA-treated AML cells, together with the increase of intracellular autophagy flux and activation of autophagy. Furthermore, autophagy inhibitors reduced DHA-induced cell death, and inhibited the level of oxidative stress by scavenging intracellular free radicals, thus inhibiting autophagy and restoring cell viability.
CONCLUSION:DHA can activate autophagic cell death of AML by inducing oxidative stress.
