The mechanisms of p21WAF1/Cip-1 expression in MOLT-4 cell line induced by TSA.
- Author:
Yi SONG
1
;
Mei-Ju LIU
;
Guo-Wei ZHAO
;
Jun-Jie QIAN
;
Yan DONG
;
Hua LIU
;
Guo-Jing SUN
;
Zhu-Zhong MEI
;
Bin LIU
;
Bao-Lei TIAN
;
Zhi-Xian SUN
Author Information
1. Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China.
- Publication Type:Journal Article
- MeSH:
Apoptosis;
drug effects;
Blotting, Western;
Cell Cycle;
drug effects;
Cell Line, Tumor;
Cyclin-Dependent Kinase Inhibitor p21;
biosynthesis;
Enzyme Inhibitors;
pharmacology;
Flow Cytometry;
Histone Deacetylase Inhibitors;
Humans;
Hydroxamic Acids;
pharmacology;
Leukemia, Myeloid;
metabolism;
pathology
- From:
Journal of Experimental Hematology
2005;13(2):174-181
- CountryChina
- Language:Chinese
-
Abstract:
To investigate the function and molecular mechanism of p21(WAF1/Cip-1) expression in MOLT-4 cells induced by HDAC inhibitor TSA, the expression pattern of p21(WAF1/Cip-1) and the distribution of cell cycle in TSA treated cells were analyzed. The results showed that TSA could effectively induce G(2)/M arrest and apoptosis of MOLT-4 cells. Kinetic experiments demonstrated that p21(WAF1/Cip-1) were upregulated quickly before cell arrested in G(2)/M and began decreasing at the early stage of apoptosis. Meanwhile, the proteasome inhibitor MG-132 could inhibit the decrease of p21(WAF1/Cip-1) at the early stage of apoptosis, which showed that proteasome pathway involved in p21(WAF1/Cip-1) degradation during the TSA induced G(2)/M arrest and apoptosis responses. This study also identified that the protein level of p21(WAF1/Cip-1) was highly associated with the cell cycle change induced by TSA. Compared to cells treated by TSA only, exposure MOLT-4 cells to TSA meanwhile treatment with MG-132 increased the protein level of p21(WAF1/Cip-1) and increased the numbers of cell in G(2)/M-phase, whereas the cell apoptosis were delayed. It is concluded that p21(WAF1/Cip-1) plays a significant role in G(2)/M arrest and apoptosis signaling induced by TSA in MOLT-4 cells.
