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 ，Stein J 《BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS》

1,25-Dihydroxycholecalciferol enhances butyrate-induced p21(Waf1/Cip1) expression.

Butyrate, a short-chain fatty acid produced in the colon, as well as its prodrug tributyrin, reduce proliferation and increase differentiation of colon cancer cells. p21(Waf1/Cip1) and p27(Kip1) are negative regulators of cell cycle and are thought to have a key function in the differentiation of various cell lines. We studied the effects of butyrate on differentiation, VDR expression, as well as on p21(Waf1/Cip1) and p27(Kip1) expression in human colon cancer cells (Caco-2). Butyrate induced cell differentiation, which was further enhanced after addition of 1,25-dihydroxycholecalciferol. Synergistic effect of butyrate and dihydroxycholecalciferol in Caco-2 cells was due to butyrate-induced overexpression of VDR. While butyrate as well as dihydroxycholecalciferol increased p21(Waf1/Cip1) and p27(Kip1) expression, in contrast combined exposure of butyrate and dihydroxycholecalciferol resulted in a synergistic amplification of p21(Waf1/Cip1), but not of p27(Kip1) expression. These data imply that butyrate selectively increases p21(Waf1/Cip1) expression via upregulation of VDR in Caco-2 cells.

Gaschott T ，Wächtershäuser A ，Steinhilber D ，Stein J ... -  《BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS》

Butyrate-induced differentiation of Caco-2 cells is associated with apoptosis and early induction of p21Waf1/Cip1 and p27Kip1.

Litvak DA ，Evers BM ，Hwang KO ，Hellmich MR ，Ko TC ，Townsend CM Jr ... -  《-》

Silibinin upregulates the expression of cyclin-dependent kinase inhibitors and causes cell cycle arrest and apoptosis in human colon carcinoma HT-29 cells.

Agarwal C ，Singh RP ，Dhanalakshmi S ，Tyagi AK ，Tecklenburg M ，Sclafani RA ，Agarwal R ... -  《ONCOGENE》

A new molecular role for iron in regulation of cell cycling and differentiation of HL-60 human leukemia cells: iron is required for transcription of p21(WAF1/CIP1) in cells induced by phorbol myristate acetate.

Gazitt Y ，Reddy SV ，Alcantara O ，Yang J ，Boldt DH ... -  《JOURNAL OF CELLULAR PHYSIOLOGY》