Effect of Curcumin on Apoptosis of Acute T-Lymphoblastic Leukemia Cells induced by UMI-77 and Its Related Mechanism.
10.19746/j.cnki.issn.1009-2137.2022.03.006
- Author:
Zheng XU
1
;
Ling SONG
2
;
Yu-Hui WU
2
;
Bo CAO
2
Author Information
1. Department of Hematology, Xinyang Central Hospital, Xinyang 464000, Henan Province， China,E-mail:duanchenfor@163.com.
2. Department of Hematology, Xinyang Central Hospital, Xinyang 464000, Henan Province， China.
- Publication Type:Journal Article
- Keywords:
Mcl-1 small molecule inhibitor;
acute T-lymphoblastic leukemia;
apoptosis;
curcumin;
mitochondrial membrane potential
- MeSH:
Apoptosis;
Apoptosis Regulatory Proteins;
Caspase 3/metabolism*;
Caspase 9/pharmacology*;
Cell Line, Tumor;
Curcumin/pharmacology*;
Humans;
Myeloid Cell Leukemia Sequence 1 Protein/metabolism*;
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma;
Proto-Oncogene Proteins c-bcl-2/metabolism*;
Reactive Oxygen Species/pharmacology*;
Sulfonamides;
Thioglycolates;
bcl-2-Associated X Protein/pharmacology*
- From:
Journal of Experimental Hematology
2022;30(3):695-703
- CountryChina
- Language:Chinese
-
Abstract:
AbstractObjective: To explore the effect and mechanism of curcumin on human T-cell acute lymphoblastic leukemia (T-ALL) cell apoptosis induced by Mcl-1 small molecule inhibitors UMI-77.
METHODS:T-ALL cell line Molt-4 was cultured, and the cells were treated with different concentrations of curcumin and Mcl-1 small molecule inhibitor UMI-77 for 24 h. The MTT method was used to detect the cell survival rate after different treatment; According to the results of curcumin and UMI-77, the experimental settings were divided into control group, curcumin group (20 μmol/L curcumin treated cells), UMI-77 group (15 μmol/L Mcl-1 small molecule inhibitor UMI-77 treated cells) and curcumin+ UMI-77 group (20 μmol/L curcumin and 15 μmol/L Mcl-1 small molecule inhibitor UMI-77 treated cells), MTT method was used to detect cell proliferation inhibition rate, Annexin V-FITC/PI double staining method and TUNEL staining were used to detect cell apoptosis, DCFH-DA probe was used to detect cell reactive oxygen species, JC-1 fluorescent probe was used to detect mitochondrial membrane potential, Western blot was used to detect the expression levels of apoptosis-related proteins and Notch1 signaling pathway-related proteins.
RESULTS:After the treatment of Molt-4 cells with different concentrations of curcumin and Mcl-1 small molecule inhibitor UMI-77, the cell survival rate was decreased (P<0.05); Compared with the control group, the cell proliferation inhibition rate of the curcumin group and the UMI-77 group were increased, the apoptosis rate of cell was increased, the level of ROS was increased, the protein expression of Bax, Caspase-3 and Caspase-9 in the cells were all increased, and the protein expression of Bcl-2 was reduced (P<0.05); Compared with the curcumin group or UMI-77 group, the cell proliferation inhibition rate and apoptosis rate of the curcumin+UMI-77 group were further increased, and the level of ROS was increased. At the same time, the protein expression of Bax, Caspase-3 and Caspase-9 in the cells were all increased, the protein expression of Bcl-2 was reduced (P<0.05); In addition, the mitochondrial membrane potential of the cells after curcumin treatment was decreased, and the proteins expression of Notch1 and HES1 were reduced (P<0.05).
CONCLUSION:Curcumin can enhance the apoptosis of T-ALL cells induced by Mcl-1 small molecule inhibitor UMI-77 by reducing the mitochondrial membrane potential, the mechanism may be related to the inhibition of Notch1 signaling pathway.
