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

• Main Authors: Byler Timothy K, Leocadio Dean, Shapiro Oleg, Bratslavsky Gennady, Stodgell Christopher J, Wood Ronald W, Messing Edward M, Reeder Jay E
• Format: Article
• Language: English
• Published: BMC 2012-08-01
• Series: BMC Urology
• Subjects: Bladder cancer; Valproic acid; Thrombospondin-1, Urothelial carcinoma; Gene expression
• Online Access: http://www.biomedcentral.com/1471-2490/12/21

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>Histone deacetylase inhibitors warrant further study for the prevention or treatment of bladder cancer.</p>