Butyrate stimulates cyclin D and p21 and inhibits cyclin-dependent kinase 2 expression in HT-29 colonic epithelial cells.
Sodium butyrate, a product of colonic fermentation of dietary fiber, has been shown to inhibit cell proliferation by blocking the cells in the G1 phase of the cell cycle. However, its mechanism of action is still unknown. We found that butyrate strongly stimulated cyclin D and p21/WAF1/CIP1 expression in HT-29 human colonic adenocarcinoma cells, in a dose dependent manner. These stimulations were associated with a decrease in cyclin-dependent kinase (cdk) 2 level, whereas cdk4 and cdk6 remained unchanged. Our results suggest that the inhibition of cell cycle progression by sodium butyrate may be explained by a modulation of cell cycle regulatory proteins such as cyclin D and p21.
Siavoshian
S
S
Centre de Recherche en Nutrition Humaine de Nantes, CRI INSERM 95-08, CHU Hôtel-Dieu, France.
Blottiere
H M
HM
Cherbut
C
C
Galmiche
J P
JP
D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D042846:CDC2-CDC28 Kinases; D002352:Carrier Proteins / Q000378:metabolism; D003106:Colon / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D056741:Cyclin D; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism*; D004848:Epithelium / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D014407:Tumor Cells, Cultured
D002087:Butyrates; C493956:CDKN1A protein, human; D002352:Carrier Proteins; D056741:Cyclin D; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D011518:Proto-Oncogene Proteins; D020148:Butyric Acid; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; C495900:CDK4 protein, human; C495911:CDK6 protein, human; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; D018844:Cyclin-Dependent Kinases