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

Abstract:

: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.

authors

Gaschott T,Wächtershäuser A,Steinhilber D,Stein J

doi

10.1006/bbrc.2001.4756

subject

Has Abstract

pub_date

2001-04-27 00:00:00

pages

80-5

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(01)94756-4

journal_volume

283

pub_type

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