[Inhibitory effect of valproic acid on cell cycle of Kasumi-1 cell line and its mechanism].
OBJECTIVE
To investigate the influence of valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, on cell cycle of Kasumi-1 cells, and explore its molecular mechanism.


METHODS
Kasumi-1 cells were treated with VPA at different concentration and different time cell cycle changes were analyzed by flow cytometry. Cyclin D1 and p21(WAF1/CIP) gene, a cyclin-dependent kinase inhibitor, were determined by semi-quantitative RT-PCR and Western blot.


RESULTS
(1) VPA blocked the Kasumi-1 cells in G(0)/G(1) phase. (2) Compared with control group, 3 mmol/L VPA treated Kasumi-1 cells for different times caused their mRNA expression of cyclin D1 decreased. Treated with VPA at different concentration for 3 days, the mRNA expression decreased in a dose-dependent manner. (3) VPA induced p21(WAF1/CIP) mRNA expression increased in a time- and dose-dependent manner. The p21(WAF1/CIP) protein increased with increasing concentration of VPA at day 3. The p21(WAF1/CIP) protein significantly increased with 3 mmol/L VPA treatment for 2 d (2.498 +/- 0.240).


CONCLUSIONS
VPA can arrest Kasumi-1 cell in G(0)/G(1) phase through the regulation of cyclin D1 and p21(WAF1/CIP).
Zhao
Lei
L
Department of Hematology, Affiliated Hospital of Chengde Medical College, Chengde 067000, China.
Zhang
Zhi-Hua
ZH
Zhu
Cui-Min
CM
D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D014635:Valproic Acid / Q000494:pharmacology*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D056572:Histone Deacetylase Inhibitors; D012333:RNA, Messenger; D019938:Cyclin D1; D014635:Valproic Acid