Histone deacetylase inhibitor trichostatin A inhibits the growth of bladder cancer cells through induction of p21WAF1 and G1 cell cycle arrest.
OBJECTIVE
To investigate whether Trichostatin A (TSA) possesses antitumor activity against human bladder cancer cells, and if any, its mechanism.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Li
Gong-Cheng
GC
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Zhang
Xu
X
Pan
Tie-Jun
TJ
Chen
Zhong
Z
Ye
Zhang-Qun
ZQ
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D016193:G1 Phase / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; C012589:trichostatin A; D006655:Histone Deacetylases