[Effects of sodium valproate on proliferation and apoptosis of human myelodysplastic syndromes cell line MUTZ-1].
OBJECTIVE
Myelodysplastic syndromes (MDS) are heterogeneous disorders with the expansion of malignant clones. No satisfactory treatment for MDS is available. Sodium valproate (VPA) can inhibit the proliferation of tumor cells by inducing G(0)/G(1) phase arrest and cell apoptosis. This study was to investigate the effects of VPA on the proliferation of MDS cell line MUTZ-1, and explore possible mechanisms.


METHODS
MUTZ-1 cells were treated with VPA. Cell proliferation was determined by MTT assay. Cell morphology was observed under microscope and transmission electron microscope. Cell apoptosis and cell cycle were analyzed by flow cytometry (FCM). The expression of p21(WAF1) (cyclin-dependent kinase inhibitor) was detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot.


RESULTS
VPA inhibited the proliferation of MUTZ-1 cells in concentration-and time-dependent manners. When treated with 4 mmol/L VPA for 72 h, typical apoptotic morphologic features appeared in MUTZ-1 cells: condensation of cells and nuclear chromatin, disintegration of nuclear chromatin, and apoptotic bodies were observed under microscope; aggregation and margination of apoptotic nuclear chromatin, cytoplasm condensation, and irregular chromatin masses were observed under transmission electron microscope. The apoptosis rate was significantly higher in the cells treated with 1, 2, and 4 mmol/L VPA for 72 h than in untreated cells [(3.14+/-0.87)%, (14.90+/-1.04)% and (22.46+/-1.74)% vs. (0.99+/-0.35)%, P<0.05]. After treatment of VPA, cell cycle was arrested obviously at G0/G1 phase (P<0.05)û the mRNA and protein levels of p21(WAF1) were up-regulated in MUTZ-1 cells (P<0.05).


CONCLUSIONS
VPA could induce G(0)/G(1) phase arrest, inhibit the proliferation and induce the apoptosis of MUTZ-1 cells in vitro. The mechanism may be associated with the up-regulation of p21(WAF1).
Chen
Bao-An
BA
Department of Hematology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, 210009, PR China. cba8888@hotmail.com
Zhao
Hui-Hui
HH
Gao
Chong
C
Shao
Ze-Ye
ZY
Xia
Guo-Hua
GH
Dohner
Konstanze
K
D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D013995:Time; D014635:Valproic Acid / Q000494:pharmacology*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D012333:RNA, Messenger; D014635:Valproic Acid