Effect of realgar on induction of apoptosis in DLBCL cell line SU-DHL-4 and its possible mechanisms.
10.7534/j.issn.1009-2137.2014.03.029
- Author:
Li-Li SHI
1
;
Hua-Chao ZHU
1
;
Mei ZHANG
1
;
Yang-Feng LIU
1
;
Yuan WANG
1
;
Jing ZHAO
1
;
Fei LEI
2
;
Peng-Cheng HE
3
,
4
Author Information
1. Department of Hematology, The First Affiliated Hospital, Xi'an Jiaotong University Medical College, Xi'an 710061, Shaanxi Province, China.
2. Stomatologic Medical College of Lanzhou University, Lanzhou 730000, Gansu Province, China.
3. Department of Hematology, The First Affiliated Hospital, Xi'an Jiaotong University Medical College, Xi'an 710061, Shaanxi Province, China. E-mail:hepc@
4. com.
- Publication Type:Journal Article
- MeSH:
Apoptosis;
drug effects;
Arsenicals;
pharmacology;
Caspase 3;
metabolism;
Cell Line, Tumor;
Cell Proliferation;
drug effects;
Flow Cytometry;
Humans;
Leukemia, Lymphocytic, Chronic, B-Cell;
metabolism;
pathology;
Proto-Oncogene Proteins c-bcl-2;
metabolism;
Sulfides;
pharmacology;
bcl-2-Associated X Protein;
metabolism
- From:
Journal of Experimental Hematology
2014;22(3):729-734
- CountryChina
- Language:Chinese
-
Abstract:
This study was aimed to explore the effect of realgar (As4S4) on growth inhibition and apoptosis induction of DLBCL cell line SU-DHL-4 and its mechanisms. The inhibitory effect of realgar on the cell growth were detected by MTT method. The morphological changes of SU-DHL-4 were observed by transmission electron microscopy (TEM). The apoptosis of SU-DHL-4 cells treated with realgar were detected by flow cytometry with Annexin V-FITC/PI double staining and DNA agarose gel electrophoresis. The cell cycle was examined by flow cytometry with PI staining. The expressions of apoptosis-related proteins (BCL-2 , Caspase-3,BAX) were detected by Western blot. The results showed that the realgar at the concentration of 20, 40, 80 µmol/L all could inhibit the proliferation of SU-DHL-4 (P < 0.05), and in a certain time and concentration range, the inhibition rate was enhanced in a time and dose dependent manner(r = 0.982). Flow cytometric test results showed that realgar could induce SU-DHL-4 cell apoptosis after treating for 48 hours, and the apoptosis rate increased with the increasing of drug concentration (P < 0.05). After treating SU-DHL-4 cells with Realgar for 48 h, the cell cycle was blocked in the S phase (P < 0.05). TEM results revealed that when treated with realgar for 48 h, the typically apoptosis morphology-apoptotic bodies were observed in all drug-treated group, furthermore, some necrotic cells in the 80 µmol/L group were observed. After intervened by realgar for 48 h, the DNA Ladder pattern was seen according to agarose gel electrophoresis. Western blot showed that the expression of Bcl-2 protein was down-regulated while the expressions of BAX and Caspase-3 protein were up-regulated when treating SU-DHL-4 cells with realgar for 48 h. It is concluded that realgar can inhibit cell growth and induce cell apoptosis, which may be related with up-regulation of Caspase-3 and BAX expression and down-regulation the of BCL-2 expression.
