Sodium butyrate induces NIH3T3 cells to senescence-like state and enhances promoter activity of p21WAF/CIP1 in p53-independent manner.
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.
Xiao
H
H
Department of Basic Gerontology, National Institute for Longevity Sciences, 36-3 Gengo, Morioka-Cho, Obu, Japan.
Hasegawa
T
T
Miyaishi
O
O
Ohkusu
K
K
Isobe
K i
Ki
D016475:3T3 Cells; D000818:Animals; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D016922:Cellular Senescence / Q000187:drug effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D016158:Genes, p53; D051379:Mice; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D017384:Sequence Deletion
D002087:Butyrates; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D012333:RNA, Messenger; D020148:Butyric Acid