Effect of a Novel Dihydroartemisinin Dimer Containing Nitrogen Atoms SM 1044 on Apoptosis of Human Leukemia Cell Line NB4-R1.
10.19746/j.cnki.issn.1009-2137.2023.03.007
- Author:
Wen CUI
1
,
2
,
3
;
Zheng XUE
4
;
Ling-Ling ZHAO
5
;
Ying LI
6
;
Jian-Qing MI
7
Author Information
1. Department of Pediatrics, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China
2. Department of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Hematology, Shanghai 200025, China
3. Department of Clinical Laboratory, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China.
4. Department of Pediatrics, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China .E-mail: xz695@163.com.
5. Department of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Hematology, Shanghai 200025, China.
6. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
7. Department of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Hematology, Shanghai 200025, China .E-mail: jianqingmi@shsmu.edu.cn.
- Publication Type:Journal Article
- Keywords:
NB4-R1 cells;
acute promyelocytic leukemia;
artemisinin derivatives;
cell apoptosis
- MeSH:
Humans;
Reactive Oxygen Species/pharmacology*;
Tretinoin/pharmacology*;
Leukemia, Promyelocytic, Acute;
Cell Line;
Apoptosis;
Oncogene Proteins, Fusion;
Cell Differentiation
- From:
Journal of Experimental Hematology
2023;31(3):659-665
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the effect of a water-soluble novel dihydroartemisinin dimer containing nitrogen atoms SM 1044 on the apoptosis of all-trans retinoic acid (ATRA) resistant acute promyelocytic leukemia (APL) NB4-R1 cells and its potential mechanism.
METHODS:The effects of SM 1044 on cell apoptosis, mitochondrial transmembrane potential, and the level of reactive oxygen species (ROS) were assessed by flow cytometry. Expressions of apoptosis-related proteins were determined by Western blot. The effects of SM 1044 on MAPK (ERK, JNK) signaling pathway, PML/RARα fusion protein, and expressions of apoptosis-related proteins were detected by Western blot.
RESULTS:SM 1044 could significantly induce apoptosis and the loss of mitochondrial transmembrane potential in NB4-R1 cells, and activate apoptosis-related proteins caspase-3, caspase-8, caspase-9 and poly (ADP-ribose) polymerase (PARP). SM 1044 could also induce NB4-R1 cells to produce ROS. Western blot showed that SM 1044 activated the phosphorylation of MAPK (ERK, JNK) signaling pathway and down-regulated the expression of PML/RARα fusion protein.
CONCLUSION:SM 1044 can induce apoptosis of ATRA resistant APL NB4-R1 cells, which may be related to ROS/ERK and ROS/JNK signaling pathway, and can also induce by down-regulating PML/RARα fusion protein.
