Tributyrin, an oral butyrate analogue, induces apoptosis through the activation of caspase-3.
The purpose of this study was to investigate the anti-proliferative and pro-apoptotic effects of the butyrate analogues, tributyrin (TB) and phenylbutyrate (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 activity. A block in the G1/S cell cycle traverse associated with a decrease in CDK2 (cyclin dependent kinase) protein levels and retinoblastoma protein hypophosphorylation was also noted after PB and TB exposure. Importantly, TB proved to be the most potent agent in its ability to induce these phenotypic changes, and potentially may represent a novel therapy for patients with advanced colorectal cancer.
Clarke
K O
KO
Department of Surgery, UMDNJ--New Jersey Medical School, 185 South Orange Avenue, MSB G588, Newark, NJ 07103, USA.
Feinman
R
R
Harrison
L E
LE
D000230:Adenocarcinoma / Q000201:enzymology / Q000473:pathology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002087:Butyrates / Q000494:pharmacology; D042846:CDC2-CDC28 Kinases; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D018797:Cell Cycle Proteins; D003110:Colonic Neoplasms / Q000201:enzymology / Q000473:pathology; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D050684:E2F Transcription Factors; D050704:E2F4 Transcription Factor; D004789:Enzyme Activation / Q000187:drug effects; D016193:G1 Phase / Q000187:drug effects; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D010641:Phenotype; D010654:Phenylbutyrates / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014280:Triglycerides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology
D000970:Antineoplastic Agents; D002087:Butyrates; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050704:E2F4 Transcription Factor; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D010654:Phenylbutyrates; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D014280:Triglycerides; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D053148:Caspase 3; D020169:Caspases; C005830:tributyrin