The Effect and Mechanism of Novel Telomerase Inhibitor Nilo 22 on Leukemia Cells.
10.19746/j.cnki.issn.1009-2137.2021.04.007
- Author:
Jing-Jing YIN
1
;
Qian TANG
2
;
Jia-Li GU
1
;
Ya-Fang LI
1
;
Hui-Er GAO
3
;
Mei HE
1
;
Ming YANG
1
;
Wen-Shan ZHANG
1
;
Hui XU
1
;
Chao-Qun WANG
1
;
Ying-Hui LI
1
;
Cui-Gai BAI
4
;
Ying-Dai GAO
5
Author Information
1. State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Disease Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
2. High-throughput Molecular Drug Discovery Center, Tianjin International Joint Academy of Biomedicine, Tianjin 300457, China.
3. State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Disease Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China,Department of Pharmacy, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin 300192, China.
4. High-throughput Molecular Drug Discovery Center, Tianjin International Joint Academy of Biomedicine, Tianjin 300457, China,E-mail: baicuigai@tjab.org.
5. State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Disease Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China,E-mail: ydgao@ihcams.ac.cn.
- Publication Type:Journal Article
- MeSH:
Animals;
Apoptosis/drug effects*;
Cell Cycle/drug effects*;
Cell Line, Tumor;
Humans;
Leukemia;
Mice;
Myeloid-Lymphoid Leukemia Protein/genetics*;
Telomerase/metabolism*;
Telomere/metabolism*
- From:
Journal of Experimental Hematology
2021;29(4):1056-1064
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the cytotoxic effect and its mechanism of the micromolecule compound on the leukemia cells.
METHODS:The cytotoxic effects of 28 Nilotinib derivatives on K562, KA, KG, HA and 32D cell lines were detected by MTT assays, and the compound Nilo 22 was screen out. Cell apoptosis and cell cycle on leukemia cells were detected by flow cytometry. The effect of compound screened out on leukemogenesis potential of MLL-AF9 leukemia mice GFP
RESULTS:Nilo 22 serves as the most outstanding candidate out of 28 Nilotinib derivatives, which impairs leukemia cell lines, but spares normal hematopoietic cell line. Comparing with Nilotinib, Nilo 22 could induce the apoptosis of GFP
CONCLUSION:Nilo 22 shows a significant cytotoxic effect on mice and human leukemia cells, especially for drug resistance cells. Nilo 22 is a promising anti-leukemia agent to solve the common clinical problems of drug resistance and relapse of leukemia.
