title: [The mechanisms of p21WAF1/Cip-1 expression in MOLT-4 cell line induced by TSA].
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.
authors.affiliation: Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Song
authors.forename: Mei-Ju
authors.initials: MJ
authors.lastname: Liu
authors.forename: Guo-Wei
authors.initials: GW
authors.lastname: Zhao
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Qian
authors.forename: Yan
authors.initials: Y
authors.lastname: Dong
authors.forename: Hua
authors.initials: H
authors.lastname: Liu
authors.forename: Guo-Jing
authors.initials: GJ
authors.lastname: Sun
authors.forename: Zhu-Zhong
authors.initials: ZZ
authors.lastname: Mei
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Bao-Lei
authors.initials: BL
authors.lastname: Tian
authors.forename: Zhi-Xian
authors.initials: ZX
authors.lastname: Sun
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007951:Leukemia, Myeloid / Q000378:metabolism / Q000473:pathology
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C012589:trichostatin A