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

Biochem Biophys Res Commun. 2001 Apr 27;283(1):80-5. doi: 10.1006/bbrc.2001.4756.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Blotting, Western
  • Butyrates / pharmacology*
  • Caco-2 Cells / cytology
  • Caco-2 Cells / drug effects*
  • Caco-2 Cells / metabolism
  • Calcitriol / pharmacology*
  • Cell Cycle Proteins*
  • Cell Differentiation / drug effects
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclins / metabolism*
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Humans
  • Microtubule-Associated Proteins / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Calcitriol / biosynthesis
  • Receptors, Calcitriol / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Triglycerides / pharmacology
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins*
  • Up-Regulation / drug effects


  • Butyrates
  • CDKN1A protein, human
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Microtubule-Associated Proteins
  • RNA, Messenger
  • Receptors, Calcitriol
  • Triglycerides
  • Tumor Suppressor Proteins
  • Cyclin-Dependent Kinase Inhibitor p27
  • Alkaline Phosphatase
  • Calcitriol
  • tributyrin