Suberoylanilide hydroxamic acid (SAHA) is the prototype of a family of hybrid polar compounds that induce growth arrest in transformed cells and show promise for the treatment of
cancer. SAHA induces differentiation and/or apoptosis in certain transformed cells in culture and is a potent inhibitor of
histone deacetylases. In this study, we examined the effects of SAHA on the growth of human
prostate cancer cells in culture and on the growth of the CWR22 human prostate xenograft in nude mice. SAHA suppressed the growth of the LNCaP, PC-3, and TSU-Pr1 cell lines at micromolar concentrations (2.5-7.5 microM). SAHA induced dose-dependent cell death in the LNCaP cells. In mice with transplanted CWR222 human prostate
tumors, SAHA (25, 50, and 100 mg/kg/day) caused significant suppression of
tumor growth compared with mice receiving vehicle alone; treatment with 50 mg/kg/day resulted in a 97% reduction in the mean final
tumor volume compared with controls. At this dose, there was no detectable toxicity as evaluated by
weight gain and necropsy examination. Increased accumulation of acetylated core
histones was detected in the CWR22
tumors within 6 h of SAHA administration. SAHA induced
prostate-specific antigen mRNA expression in CWR22
prostate cancer cells, resulting in higher levels of serum
prostate-specific antigen than predicted from
tumor volume alone. The results suggest that
hydroxamic acid-based hybrid polar compounds inhibit
prostate cancer cell growth and may be useful, relatively nontoxic agents for the treatment of prostate
carcinoma.