1.
Butyrate is a well known product of
starch fermentation by colonic bacteria and is of interest owing to its ability to induce in vitro apoptosis and cell differentiation, as well as to inhibit cell growth in colorectal and other
cancer cells. Synthetic analogues of
butyrate may also possess cellular activities in a variety of cultured cells. The aim of the present study was to evaluate the effects of
butyrate analogues on apoptosis, proliferation and
histone deacetylase (HDAC) activity in HT-29
colorectal cancer cells. In addition, the effects of these analogues on
lactate dehydrogenase leakage, as a measure of non-specific cytotoxicity, were evaluated in HT-29 cells. 2. Of the 26 analogues examined, four (
propionate, 4-benzoylbutyrate, 4-(4-aminophenyl)
butyrate and benzyloxyacetate) exhibited comparable effects to
butyrate. Interestingly, no activity was noted for compounds carrying amino,
hydroxyl or methyl substitutions at the 2-, 3- or 4-position of the aliphatic moiety of
butyrate. 3. In conclusion, chemical changes to the structure of
butyrate can significantly modify the
biological activity assayed in HT-29
colorectal cancer cells in vitro.