Effect of Dihydroartemisinin and Arsenic Trioxide on Apoptosis of Acute Myeloid Leukemia Cells.
10.19746/j.cnki.issn.1009-2137.2022.05.006
- Author:
Wei-Dong SUN
1
,
2
;
Xin WANG
3
;
Ying WANG
3
;
Xiang-Min TONG
4
Author Information
1. Department of Hematology, Shaoxing Central Hospital, Shaoxing 321030, Zhejiang Province, China
2. Key Laboratory of Molecular Diagnosis and Individualization of Cancer, Zhejiang Provincial People's Hospital, Hangzhou 310014, Zhejiang Province, China.
3. Key Laboratory of Molecular Diagnosis and Individualization of Cancer, Zhejiang Provincial People's Hospital, Hangzhou 310014, Zhejiang Province, China.
4. Key Laboratory of Molecular Diagnosis and Individualization of Cancer, Zhejiang Provincial People's Hospital, Hangzhou 310014, Zhejiang Province, China.E-mail: tongxiangmin11@163.com.
- Publication Type:Journal Article
- Keywords:
FLT3-ITD mutant;
acute myeloid leukemia;
apoptosis;
arsenic trioxide;
dihydroartemisinin
- MeSH:
Apoptosis;
Arsenic Trioxide/therapeutic use*;
Artemisinins/therapeutic use*;
Cell Line, Tumor;
Humans;
Leukemia, Myeloid, Acute/drug therapy*;
Myeloid Cell Leukemia Sequence 1 Protein;
Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use*;
Reactive Oxygen Species/therapeutic use*;
Sincalide/therapeutic use*;
fms-Like Tyrosine Kinase 3
- From:
Journal of Experimental Hematology
2022;30(5):1337-1342
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the effect of dihydroartemisinin (DHA) combined with arsenic trioxide (ATO) on the viability and apoptosis of acute myeloid leukemia (AML) FLT3-ITD mutant cell line MOLM13 and its mechanism.
METHODS:MOLM13 cells were treated with DHA or ATO alone or in combination. The viability of MOLM13 cells was detected by CCK-8 assay, cell proliferation was observed by colony formation assay, cell apoptosis and reactive oxygen species (ROS) level were measured by flow cytometry, and the expression levels of proteins related to apoptosis were detected by Western blot.
RESULTS:Compared with the control group, treatment with DHA and ATO alone or in combination could inhibit cell proliferation, activate ROS formation, and finally induce cell apoptosis. DHA in combination with ATO produced a synergistic effect. Western blot analysis showed that DHA combined with ATO could significantly upregulate the level of c-PARP and activate apoptosis via inhibition of Mcl-1 and FLT3-ITD.
CONCLUSION:DHA combined with ATO induces the apoptosis of FLT3-ITD AML cell line MOLM13 by inhibiting Mcl-1 pathway and activating FLT3-ITD protein degradation.
