Article

Histone deacetylase inhibitor trichostatin A inhibits the growth of bladder cancer cells through induction of p21WAF1 and G1 cell cycle arrest.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
International Journal of Urology (impact factor: 1.75). 06/2006; 13(5):581-6. DOI:10.1111/j.1442-2042.2006.01344.x pp.581-6
Source: PubMed

ABSTRACT To investigate whether Trichostatin A (TSA) possesses antitumor activity against human bladder cancer cells, and if any, its mechanism.
A human bladder cancer cell line, BIU-87, was treated with different concentrations of TSA. After treatment, cell growth was measured by MTT assay. Cell apoptosis and cell cycle changes were examined by means of flow cytometry (FCM). Apoptosis was confirmed by apoptotic ladder formation assay. mRNA expression of p21WAF1 and p53 was assessed by differential reverse transcription-polymerase chain reaction.
Trichostatin A significantly inhibited the proliferation of bladder cancer cell at nanomolar concentrations in a time- and dose-dependent fashion. TSA treatment caused cell cycle arrest at the G1 phase and increased apoptotic cell death as shown by FCM and DNA fragmentation analysis, accompanied by increased p21WAF1 mRNA expression. In addition, TSA treatment did not alter p53 mRNA expression.
Our results indicate that TSA is able to inhibit bladder cancer cell growth in vitro, possibly through p21WAF1 mediated cell cycle arrest and apoptotic cell death. This study suggests that TSA may be a potential therapeutic agent for the treatment of bladder cancer.

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Keywords

apoptotic cell death
 
apoptotic ladder formation assay
 
bladder cancer
 
bladder cancer cell
 
bladder cancer cell growth
 
Cell apoptosis
 
cell cycle arrest
 
cell cycle changes
 
cell growth
 
DNA fragmentation analysis
 
flow cytometry
 
G1 phase
 
human bladder cancer cell line
 
human bladder cancer cells
 
mRNA expression
 
MTT assay
 
p21WAF1 mRNA expression
 
p53 mRNA expression
 
potential therapeutic agent
 
TSA treatment