Efficacy of butyrate analogues in HT-29 cancer cells.
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.
Ooi
Cheng C
CC
CSIRO Preventative Health Flagship, Sansom Institute, University of South Australia, Adelaide, South Australia, Australia.
Good
Norm M
NM
Williams
Desmond B
DB
Lewanowitsch
Tanya
T
Cosgrove
Leah J
LJ
Lockett
Trevor J
TJ
Head
Richard J
RJ
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002087:Butyrates / Q000737:chemistry / Q000494:pharmacology*; D020148:Butyric Acid / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D019073:HT29 Cells; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D045022:Lactate Dehydrogenases / Q000378:metabolism; D013223:Statistics as Topic; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D002087:Butyrates; D056572:Histone Deacetylase Inhibitors; D020148:Butyric Acid; C551236:4-benzoylbutyric acid; D045022:Lactate Dehydrogenases; D006655:Histone Deacetylases