Histone deacetylase inhibitors (HDACis) are emerging as a promising new class of 
anticancer agents displaying growth-inhibitory activity and low toxicity in 
vivo. In this study, we examined the effect of sodium butyrate (NaB) and 
trichostatin A (TSA) on the growth of human bladder carcinoma cell lines in 
culture and TSA on the growth of EJ and UM-UC-3 human bladder xenografts in nude 
mice. NaB and TSA suppressed the growth of bladder cell lines at millimolar 
(1.5-4.3 mM) and micromolar (0.03-0.33 microM) concentrations, respectively, 
inducing concentration-dependent cell death. Bladder carcinoma cells within the 
experimental panel displayed the phenotype of late-stage bladder lesions 
expressing N-cadherin in the absence of E-cadherin accompanied by low levels of 
plakoglobin expression. Exposure of these cells to HDACis resulted in 
upregulation of plakoglobin with no change in E-cadherin expression. A 2-hr 
exposure to TSA was the minimal time required to upregulate plakoglobin in cells 
with downregulation to baseline levels occurring within 24 hr following drug 
removal. In mice bearing EJ and UM-UC-3 bladder xenografts, TSA (500 
microg/kg/day) caused suppression of tumor growth compared with mice receiving 
vehicle alone. A > 70% reduction in mean final tumor volume was recorded in both 
bladder xenograft models with no detectable toxicity. The results suggest that 
TSA inhibits bladder carcinoma cell growth and may be a useful, relatively 
nontoxic agent for consideration in the treatment of late-stage bladder tumors.