The purpose of this study was to investigate the anti-proliferative and pro
-apoptotic effects of the butyrate analogues, tributyrin (TB) and phenylbut
yrate (PB), in a colon cancer model. We demonstrate that HT-29 colon cancer
cells exposed to PB and TB result in growth inhibition associated with an
induction of apoptosis mediated through the activation of caspase-3 activit
y. A block in the GUS cell cycle traverse associated with a decrease in CDK
2 (cyclin dependent kinase) protein levels and retinoblastoma protein hypop
hosphorylation was also noted after PB and TB exposure. Importantly, TB pro
ved to be the most potent agent in its ability to induce these phenotypic c
hanges, and potentially may represent a novel therapy for patients with adv
anced colorectal cancer. (C) 2001 Elsevier Science Ireland Ltd. All rights
reserved.