Histone Deacetylase Inhibition Selectively Alters the Activity and Expression of Cell Cycle Proteins Leading to Specific Chromatin Acetylation and Antiproliferative Effects

Sambucetti, Lidia; Fischer, Denise; Zabludoff, Sonya; Kwon, Paul; Chamberlin, Helena; Trogani, Nancy; Xu, Hong; Cohen, Dalia

doi:10.1074/jbc.274.49.34940

Cited by 370 publications

(299 citation statements)

References 58 publications

Supporting

Mentioning

282

Contrasting

Unclassified

Order By: Relevance

“…HDAC4 silencing induces expression of p21 WAF1/Cip1 mRNA and protein HDAC inhibitors induce p21 WAF1/Cip1 in many cancer cell lines Sowa et al, 1997;Archer et al, 1998;Kim et al, 1999;Sambucetti et al, 1999;Han et al, 2000;Huang and Pardee, 2000;Richon et al, 2000;Sawa et al, 2004;Rocchi et al, 2005) and inhibit class I and class II HDACs equally well. To identify the specific HDACs that participate in regulating p21 WAF1/Cip1 , we transfected IGROV-1 cells with siRNAs directed against seven class I and II HDACs (HDAC1 through HDAC7) (Supplementary Figure S1A and B) and examined p21 WAF1/Cip1 by real-time polymerase chain reaction (RT-PCR) and western blot analysis.…”

Section: Resultsmentioning

confidence: 99%

“…As HDAC inhibitors regulate p21 WAF1/Cip1 gene transcription by modifying histone acetylation in the Kim et al, 1999;Sambucetti et al, 1999;Richon et al, 2000;Sawa et al, 2004), we used chromatin immunoprecipitation assays to analyse histone H3 acetylation at the Sp1/ Sp3-binding sites-rich region of the p21 WAF1/Cip1 promoter in HDAC4-silenced HeLa cells. Efficient HDAC4-silencing (Figure 4d, left) significantly increased histone H3 acetylation at the p21 WAF1/Cip1 promoter but not at the actin promoter used as a negative control (Figure 4d, right).…”

Section: Sp3 S Ir N a E G T / E G T S Ir N A H D A C 4 / E G T S Ir Nmentioning

confidence: 99%

“…Among the genes that are consistently upregulated in cancer cells treated with HDAC inhibitors is the cell cycle mediator p21 WAF1/Cip1 Sowa et al, 1997;Archer et al, 1998;Kim et al, 1999;Saito et al, 1999;Sambucetti et al, 1999;Richon et al, 2000;Han et al, 2001;Rocchi et al, 2005). p21 WAF1/Cip1 arrests cell growth by inhibiting cyclin/Cdk complexes (Xiong et al, 1993) and can act as tumor suppressor gene by negatively regulating the cell cycle.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

HDAC4 represses p21WAF1/Cip1 expression in human cancer cells through a Sp1-dependent, p53-independent mechanism

et al. 2008

View full text Add to dashboard Cite

Cancer cells have complex, unique characteristics that distinguish them from normal cells, such as increased growth rates and evasion of anti-proliferative signals. Global inhibition of class I and II histone deacetylases (HDACs) stops cancer cell proliferation in vitro and has proven effective against cancer in clinical trials, at least in part, through transcriptional reactivation of the p21 WAF1/Cip1 gene. The HDACs that regulate p21 WAF1/Cip1 are not fully identified. Using small interfering RNAs, we found that HDAC4 participates in the repression of p21 WAF1/Cip1 through Sp1/Sp3-, but not p53-binding sites. HDAC4 interacts with Sp1, binds and reduces histone H3 acetylation at the Sp1/Sp3 binding site-rich p21 WAF1/Cip1 proximal promoter, suggesting a key role for Sp1 in HDAC4-mediated repression of p21 WAF1/Cip1 . Induction of p21 WAF1/Cip1 mediated by silencing of HDAC4 arrested cancer cell growth in vitro and inhibited tumor growth in an in vivo human glioblastoma model. Thus, HDAC4 could be a useful target for new anti-cancer therapies based on selective inhibition of specific HDACs.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Sp3 S Ir N a E G T / E G T S Ir N A H D A C 4 / E G T S Ir Nmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

HDAC4 represses p21WAF1/Cip1 expression in human cancer cells through a Sp1-dependent, p53-independent mechanism

et al. 2008

View full text Add to dashboard Cite

show abstract

“…In addition, the majority of the treated cells remained in cell cycle for 3 days after the addition of sodium butyrate, but the cycling fraction decreased to 17% 7 days later [Rambhatla et al, 2003]. It was now established that treatment of cells both in vitro and in vivo with sodium butyrate, a potential histone deacetylase (HDAC) inhibitor, could result in specific functional outcomes such as proliferation, cell cycle arrest, apoptosis, or differentiation [Janson et al, 1997;Sambucetti et al, 1999;Wang et al, 1999;Travers et al, 2002;Camphausen et al, 2004;Hsieh et al, 2004;Bug et al, 2005;Cho et al, 2005;Jiang et al, 2005;Rossig et al, 2005]. Therefore it was assumed that the treatment with sodium butyrate would lead to the cell cycle arrest of the ES cells, and the removal of sodium butyrate might be important for the treated cells to reenter into cell cycle and consequently the cells with the capacity to proliferate and express hepatic linage markers could be acquired.…”

mentioning

confidence: 99%

In vitro differentiation of hepatic progenitor cells from mouse embryonic stem cells induced by sodium butyrate

Zhou

Xiang

Shao

et al. 2006

J of Cellular Biochemistry

View full text Add to dashboard Cite

Recently it was shown that embryonic stem (ES) cells could differentiate into hepatocytes both in vitro and in vivo, however, prospective hepatic progenitor cells have not yet been isolated and characterized from ES cells. Here we presented a novel 4-step procedure for the differentiation of mouse ES cells into hepatic progenitor cells and then hepatocytes. The differentiated hepatocytes were identified by morphological, biochemical, and functional analyses. The hepatic progenitor cells were isolated from the cultures after the withdrawal of sodium butyrate, which was characterized by scant cytoplasm, ovoid nuclei, the ability of rapid proliferation, expression of a series of hepatic progenitor cell markers, and the potential of differentiation into hepatocytes and bile duct-like cells under the proper conditions that favor hepatocyte and bile epithelial differentiation. The differentiation of hepatocytes from hepatic progenitor cells was characterized by a number of hepatic cell markers including albumin secretion, upregulated transcription of glucose-6-phophatase and tyrosine aminotransferase, and functional phenotypes such as glycogen storage. The results from our experiments demonstrated that ES cells could differentiate into a novel bipotential hepatic progenitor cell and mature into hepatocytes with typical morphological, phenotypic and functional characteristics, which provides an useful model for the studies of key events during early liver development and a potential source of transplantable cells for cell-replacement therapies.

show abstract

“…However, the reports in the literature about the role of p53 in the sodium butyrate-mediated growth inhibition of cells are unclear. While some studies suggest a possible role for p53 in HDIs-mediated growth inhibition, [21][22][23][24][25] others suggest p53 is not required. [26][27][28] In our study, we provide evidence for an important role for p53 pathway in sodium butyrate-mediated growth suppression.…”

mentioning

confidence: 99%

Role of p53 status in chemosensitivity determination of cancer cells against histone deacetylase inhibitor sodium butyrate

Joseph

Wajapeyee

Somasundaram

2005

Intl Journal of Cancer

View full text Add to dashboard Cite

Histone deacetylases inhibitors (HDIs) induce growth arrest and apoptosis in a variety of human cancer cells. Sodium butyrate (NaB), a histone deacetylase inhibitor, has been shown to cause a G 1 cell cycle arrest by inducing p21 WAF1/CIP1 in a p53-independent manner. In this report, we present evidence for activation of p53 pathway by NaB and its role in the NaB-mediated growth suppression. Addition of NaB increased the levels of p53 involving a p14 ARF -dependent post-transcriptional mechanism. NaB induced p53 is functional as it activated p53-specific reporter, induced the level of p21 WAF1/CIP1 , inhibited cellular DNA synthesis and induced apoptosis. By using HPV 16 E6 stable transfectants as well as p53 null cancer cells, we show that NaB suppresses the growth of WT p53 containing cells more efficiently. NaB inhibited DNA synthesis to similar extent both in the presence and absence of p53. However, NaB treatment lead to a major G 2 /M arrest of cells in the presence of p53, while cells without wild-type p53 accumulated mainly in G 1 phase of the cell cycle. Furthermore, apoptosis induction by NaB is greatly reduced in the absence of p53. These results suggest that p53 pathway mediates in part growth suppression by NaB and the p53 status may be an important determinant of chemosensitivity in HDI based cancer chemotherapy. ' 2005 Wiley-Liss, Inc.Key words: Histone deacetylase inhibitors; sodium butyrate; p53; apoptosis; growth arrest Chromatin remodeling plays an important role in transcriptional regulation. Evidence suggest that acetylation and deacetylation of histones and/or nonhistone proteins play significant roles in chromatin remodeling and thus in the regulation of transcription. 1,2 Consequently, histone acetyl transferases (HATs) and histone deacetylases (HDACs) are emerging as important molecules in transcriptional regulation. Histone deacetylases inhibitors (HDIs) are promising agents for anticancer therapy as they exhibit strong antitumor activities in vivo with low toxicity in preclinical studies. HDIs belong to a heterogenous class of compounds that includes derivatives of short chain fatty acids, hydroxamic acids, cyclic tetrapetides and benzamides.Sodium butyrate (NaB), a short chain fatty acid, is a histone deacetylase inhibitor and is produced in the colonic lumen as a consequence of microbial degradation of dietary fibers. 3,4 Sodium butyrate and other deacetylase inhibitors are not growth inhibitory to normal cells. 5,6 The growth inhibitory effect of NaB against cancer cells has been attributed to its ability to induce cell cycle arrest, differentiation and apoptosis. 7-10 NaB induced cell cycle arrest and differentiation has been correlated with its ability to induce p21 WAF1/CIP1 in a p53-independent manner 11-15 and modulate levels of cyclin D1, 12,16,17 cdc2, 17 cdk2 12,18 and proliferating cell nuclear antigen (PCNA). 19 However, the mechanism of apoptosis induction by NaB is not clearly understood. Acetylation of nontranscriptional targets such as nonhistone proteins like tubulin...

show abstract

Histone Deacetylase Inhibition Selectively Alters the Activity and Expression of Cell Cycle Proteins Leading to Specific Chromatin Acetylation and Antiproliferative Effects

Cited by 370 publications

References 58 publications

HDAC4 represses p21WAF1/Cip1 expression in human cancer cells through a Sp1-dependent, p53-independent mechanism

HDAC4 represses p21WAF1/Cip1 expression in human cancer cells through a Sp1-dependent, p53-independent mechanism

In vitro differentiation of hepatic progenitor cells from mouse embryonic stem cells induced by sodium butyrate

Role of p53 status in chemosensitivity determination of cancer cells against histone deacetylase inhibitor sodium butyrate

Contact Info

Product

Resources

About