Research article

BMC Urology

, 12:21

Open Access This content is freely available online to anyone, anywhere at any time.

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

  • Timothy K BylerAffiliated withDepartment of Urology, State University of New York Upstate Medical University
  • , Dean LeocadioAffiliated withDepartment of Urology, State University of New York Upstate Medical University
  • , Oleg ShapiroAffiliated withDepartment of Urology, State University of New York Upstate Medical University
  • , Gennady BratslavskyAffiliated withDepartment of Urology, State University of New York Upstate Medical University
  • , Christopher J StodgellAffiliated withDepartment of Obstetrics and Gynecology, University of Rochester
  • , Ronald W WoodAffiliated withDepartment of Obstetrics and Gynecology, University of Rochester
  • , Edward M MessingAffiliated withDepartment of Urology, University of Rochester
  • , Jay E ReederAffiliated withDepartment of Urology, State University of New York Upstate Medical UniversityDepartment of Obstetrics and Gynecology, University of Rochester Email author 

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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

Keywords

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