Sodium butyrate induces NIH3T3 cells to senescence-like state and enhances promoter activity of p21WAF/CIP1 in p53-independent manner

Biochem Biophys Res Commun. 1997 Aug 18;237(2):457-60. doi: 10.1006/bbrc.1997.7158.


Sodium butyrate, a histone deacetylase inhibitor, has been shown to induce differentiation of many cancer cells and senescence-like state of human fibroblasts. Here we show that sodium butyrate also induces senescence-like state of NIH3T3 cells. The treated cells were blocked at G1 phase and featured morphologically like senescent cells with enlarged cytoplasm and multiple nuclei. The expression of p21(WAF/CIP1) (p21) increased after sodium butyrate treatment at transcriptional level. To analyze the induction of promoter activity, we isolated 4.6 kb of murine p21 promoter and inserted it upstream of a luciferase reporter gene. When this construct was transiently transfected into NIH3T3 cells, sodium butyrate enhanced the luciferase activity. p53 independency of sodium butyrate-inducible p21 promoter activity was confirmed by using the deletion mutants lacking p53 binding sites and p53 deficient cells in transfection experiments.

MeSH terms

  • 3T3 Cells
  • Animals
  • Butyrates / pharmacology*
  • Butyric Acid
  • Cellular Senescence / drug effects*
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / genetics*
  • Gene Expression Regulation / drug effects
  • Genes, p53
  • Mice
  • Promoter Regions, Genetic*
  • RNA, Messenger / genetics
  • Sequence Deletion


  • Butyrates
  • Cdkn1a protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • RNA, Messenger
  • Butyric Acid