Open Access Research article

Valproic acid decreases urothelial cancer cell proliferation and induces thrombospondin-1 expression

Timothy K Byler1, Dean Leocadio1, Oleg Shapiro1, Gennady Bratslavsky1, Christopher J Stodgell2, Ronald W Wood2, Edward M Messing3 and Jay E Reeder12*

Author affiliations

1 Department of Urology, State University of New York Upstate Medical University, 750 East Adams Street, Syracuse, NY, 13210, USA

2 Department of Obstetrics and Gynecology, University of Rochester, 601 Elmwood Avenue, Rochester, NY, 14642, USA

3 Department of Urology, University of Rochester, 601 Elmwood Avenue, Rochester, NY, 14642, USA

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Citation and License

BMC Urology 2012, 12:21  doi:10.1186/1471-2490-12-21

Published: 16 August 2012



Prevention of bladder cancer recurrence is a central challenge in the management of this highly prevalent disease. The histone deacetylase inhibitor valproic acid (sodium valproate) has anti-angiogenic properties and has been shown to decrease bladder cancer growth in model systems. We have previously shown reduced expression of thrombospondin-1 in a mouse model and in human bladder cancer relative to normal urothelium. We speculated that inhibition of angiogenesis by valproate might be mediated by this anti-angiogenic protein.


Bladder cancer cell lines UMUC3 and T24 were treated with valproate or another histone deacetylase inhibitor, vorinostat, in culture for a period of three days. Proliferation was assessed by alamar blue reduction. Gene expression was evaluated by reverse transcription of RNA and quantitative PCR.


Proliferation assays showed treatment with valproate or vorinostat decreased proliferation in both cell lines. Histone deacetylase inhibition also increased relative expression of thrombospondin-1 up to 8 fold at 5 mM valproate.


Histone deacetylase inhibitors warrant further study for the prevention or treatment of bladder cancer.

Bladder cancer; Valproic acid; Thrombospondin-1, Urothelial carcinoma; Gene expression