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

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3487994PMC
http://dx.doi.org/10.1186/1471-2490-12-21DOI Listing

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