SODIUM-BUTYRATE INDUCES NIH3T3 CELLS TO SENESCENCE-LIKE STATE AND ENHANCES PROMOTER ACTIVITY OF P21(WAF CIP1) IN P53-INDEPENDENT MANNER/

Sodium butyrate, a histone deacetylase inhibitor, has been shown to in duce differentiation of many cancer cells and senescence-like state of human fibroblasts. Here we show that sodium butyrate also induces sen escence-like state of NIH3T3 cells. The treated cells were blocked at G1 phase and featured morphologically like senescent cells with enlarg ed 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 m urine p21 promoter and inserted it upstream of a luciferase reporter g ene. When this construct was transiently transfected into NIH3T3 cells , sodium butyrate enhanced the luciferase activity. p53 independency o f sodium butyrate-inducible p21 promoter activity was confirmed by usi ng the deletion mutants lacking p53 binding sites and p53 deficient ce lls in transfection experiments. (C) 1997 Academic Press.