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1459118 
Journal Article 
Sodium butyrate and tributyrin induce in vivo growth inhibition and apoptosis in human prostate cancer 
Kuefer, R; Hofer, MD; Altug, V; Zorn, C; Genze, F; Kunzi-Rapp, K; Hautmann, RE; Gschwend, JE 
2004 
Yes 
British Journal of Cancer
ISSN: 0007-0920
EISSN: 1532-1827 
90 
2 
535-541 
14735205 
WOS:000189010600043 
Histone deacetylase inhibitors (HDACs) are known to exhibit
antiproliferative effects on various carcinoma cells. In this study, the in vivo efficiency of
two HDACs, sodium butyrate and tributyrin, on prostate cancer growth inhibition were
investigated. To gain an insight into the possible underlying pathways, cell culture experiments
were per-Formed focusing on the expression of p21, Rb and c-myc. For in vivo testing, prostate
cancer cell lines (PC3 and TSU-PrI) were seeded on the chorioallantois membrane (CAM) and
implanted in a xenograft model using nude mice. Standard Western blot analysis was performed for
protein expression of p21, Rb and c-myc in HDAC-treated vs untreated prostate cancer cells. Both
sodium butyrate and tributyrin had a considerable treatment effect on microtumours on the chicken
egg at already very low concentrations of 0.1 mm. Tributyrin-treated tumours showed the strongest
effect with 38% apoptotic nuclei in the prostate cancer cell line PC3. In the mouse model, there
was almost no difference between sodium butyrate and tributyrin. In untreated animals the tumours
were almost double the size 4 weeks after implantation. Tumours of the treatment groups had a
significantly lower percentage of Ki-67-positive-stained nuclei. As demonstrated by Western blot
analysis, these effects seem to be independent of p53 status and a pathway via p21 -Rb-c-myc is
possibly involved. In this study we have demonstrated a substantial in vivo treatment effect,
which can be induced by the application of sodium butyrate or the or-ally applicable tributyrin
in human prostate cancer. The given results may provide the rationale to apply these drugs in
well-controlled clinical trials in patients being at high risk of recurrence after specific
therapy or in patients with locally or distant advanced prostate cancer. 
sodium butyrate; tributyrin; HDAC; prostate cancer; in vivo; apoptosis