Butyrate-induced differentiation of Caco-2 cells occurs independently from p27.
Butyrate, a short-chain fatty acid produced in the colon, reduces proliferation and increases differentiation of colon cancer cells. p27, an inhibitor of cyclin-dependent kinases and a negative regulator of the cell cycle, is thought to have a key function in the differentiation of various cell lines. The objective of the present study was to elucidate the role of p27 in butyrate-induced differentiation of the human colorectal carcinoma cell line Caco-2. In this report we show that in spite of the increase in p27 protein expression after incubation with the HMG-CoA reductase inhibitor mevastatin, alkaline phosphatase activity decreases significantly in this cell line. In addition, mevastatin caused a significant increase in the cell cycle inhibitor p21. All effects could be reversed by addition of mevalonate to the medium. Taken together, we provide the first evidence that in Caco-2 cells p27 may have other functions apart from the regulation of cell differentiation.
Wächtershäuser
A
A
Second Department Medicine, J. W. Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt/Main, Germany.
Stein
J
J
D017209:Apoptosis / Q000187:drug effects; D002087:Butyrates / Q000494:pharmacology*; D018938:Caco-2 Cells; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000187:drug effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000187:drug effects / Q000378:metabolism; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008869:Microtubule-Associated Proteins / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D025521:Tumor Suppressor Proteins; D015854:Up-Regulation
D002087:Butyrates; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D008869:Microtubule-Associated Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; C012258:mevastatin; D008148:Lovastatin; D006903:Hydroxymethylglutaryl CoA Reductases