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1.  Valproic acid decreases urothelial cancer cell proliferation and induces thrombospondin-1 expression 
BMC Urology  2012;12:21.
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.
doi:10.1186/1471-2490-12-21
PMCID: PMC3487994  PMID: 22898175
Bladder cancer; Valproic acid; Thrombospondin-1, Urothelial carcinoma; Gene expression

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