Inhibition of bladder tumour growth by histone deacetylase inhibitor.
OBJECTIVE
To examine the expression profile of histone deacetylase (HDAC)-1 and explore its potential role in the development of bladder cancer, using valproic acid (VPA), a HDAC inhibitor, which reduces tumour growth and metastasis formation in animal models.


METHODS
The study comprised clinical samples from patients with urinary bladder cancer, mouse urinary bladder tissue specimens, and two human urinary bladder cancer cell lines (HT-1376 and 5637). HDAC1 mRNA and protein expression were examined using real-time reverse transcription-polymerase chain reaction and immunohistochemical methods. Female C3H/He mice were given VPA (0, 250, 500 and 750 mg/kg body weight, intraperitoneal, every day) from the start or 4 weeks after 0.05%N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) treatment, and were humanely killed and sampled at 8 and 12 weeks.


RESULTS
A significantly higher level of HDAC1 mRNA was expressed in human urinary bladder cancer specimens. The immunohistochemical study showed that HDAC1 was expressed in the cytoplasm and nucleus in the specimens. BBN treatment increased HDAC1 mRNA expression in the urinary bladder. VPA administration seemed to delay the incidences of BBN-induced mouse urinary bladder tumour, possibly through p21(WAF1) protein expression.


CONCLUSIONS
These results indicate that HDAC might be an effective molecular target for cancer therapy.
Ozawa
Akira
A
Department of Urology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
Tanji
Nozomu
N
Kikugawa
Tadahiko
T
Sasaki
Toyokazu
T
Yanagihara
Yutaka
Y
Miura
Noriyoshi
N
Yokoyama
Masayoshi
M
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D056284:Histone Deacetylase 1 / Q000037:antagonists & inhibitors*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008809:Mice, Inbred C3H; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000201:enzymology* / Q000473:pathology; D014635:Valproic Acid / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D014635:Valproic Acid; D056284:Histone Deacetylase 1