Cell Cycle Arrest and Apoptosis Induced by Atovaquone in Non-Hodgkin's Lymphoma Raji Cells.
10.19746/j.cnki.issn.1009-2137.2022.06.018
- Author:
Chun-Yang CHEN
1
;
Xing SHEN
2
;
Shuang XING
2
;
Xue-Wen ZHANG
2
;
Gang JIANG
3
;
Zu-Yin YU
4
Author Information
1. Medical School, University of Electronic Science and Technology of China,Chengdu 610051, Sichuan Province, China. Institute of Radiation Medicine, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China.
2. Institute of Radiation Medicine, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China.
3. Medical School, University of Electronic Science and Technology of China,Chengdu 610051, Sichuan Province, China.E-mail: zlyyyxb@163.com.
4. Institute of Radiation Medicine, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China.E-mail: yuzy79@163.com.
- Publication Type:Journal Article
- Keywords:
Raji cell;
apoptosis;
atovaquone;
cell cycle arrest;
non-Hodgkin's lymphoma
- MeSH:
Humans;
Atovaquone/pharmacology*;
Cell Cycle Checkpoints;
Apoptosis;
Lymphoma, Non-Hodgkin
- From:
Journal of Experimental Hematology
2022;30(6):1746-1751
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the effect of atovaquone on the cell cycle and apoptosis of non-Hodgkin's lymphoma Raji cells, and clarify the related mechanisms.
METHODS:MTT assay and trypan blue dye exclusion method were used to evaluate the effect of atovaquone on the proliferation of Raji cells. After the cells were stained by PI staining, the cell cycle distribution was detected by flow cytometry. Cell apoptosis was analyzed by Annexin V/PI double binding assay. The intracellular alterations of reactive oxygen species were detected by 2', 7'-dichlorofluorescein diacetate (DCFH-DA). The protein expression of cell cycle and apoptosis related molecules were detected by Western blot.
RESULTS:Various concentrations of atovaquone (5-40 μmol/L) inhibited the growth of Raji cells in a concentration-dependent manner (r=0.951). The proliferation of Raji cells was significantly inhibited after treated by atovaquone (20 and 30 μmol/L) for 24, 48 and 72 h, which showed statistically different with that in the control group (P<0.01, P<0.001, P<0.001). G1 phase arrest (P<0.01, P<0.001) and apoptosis (P<0.01) of Raji cells was induced by atovaquone (20 and 30 μmol/L) significantly for 24 h and 48 h, respectively. The expression of p-JAK2 and p-STAT3(Y705) protein were down-regulated significantly induced by atovaquone (P<0.001, P<0.05). Furthermore, atovaquone treatment could induce the decreasing of antiapoptotic protein Mcl-1, Bcl-2, and Bcl-xl expression level (P<0.05) and increasing of cleaved caspase-3 protein expression level. In addition, atovaquone could also induce the down-regulation of c-Myc (P<0.001, P<0.01) and cell cycle related molecules Cyclin D1, CDK4, and CDK6 (P<0.01, P<0.05) protein expression.
CONCLUSION:Atovaquone effectively inhibits cell proliferation and induces cell cycle arrest and apoptosis by suppression of STAT3 signaling pathway in Raji cells. It can be a potential therapeutic agent against non-Hodgkin's lymphoma.
