The histone deacetylase inhibitor butyrate downregulates cyclin B<sub>1</sub>gene expression via a p21/WAF-1-dependent mechanism in human colon cancer cells

Archer, Sonia Y.; Johnson, Jennifer J.; Kim, Hyun-Ju; Ma, Qing; Mou, Huizhong; Vishnuvardhan, Daesety; Meng, Shufen; Hodin, Richard A.

doi:10.1152/ajpgi.00575.2004

Cited by 59 publications

(46 citation statements)

References 44 publications

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“…NaBu and other SCFAs are naturally occurring products produced by fiber fermentation in the colon and have been found to inhibit the growth of colon cancer cells both in vivo and in vitro (38). In addition, when SCFAs were applied in combination with a variety of chemotherapy drugs, better co-treatment efficacy was noted.…”

Section: Discussionmentioning

confidence: 99%

Sodium butyrate restores ASC expression and induces apoptosis in LS174T cells

Zhang

Bai

Ren

et al. 2012

International Journal of Molecular Medicine

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Abstract. Sodium butyrate (NaBu) is a short-chain fatty acid (SCFA), which has been proposed as a potential anticancer agent. Apoptosis-associated speck-like protein (ASC) is a pro-apoptotic signaling factor that is subjected to epigenetic silencing in human cancers. Modulation by the aberrant methylation of CpG islands of ASC is a well-characterized epigenetic mechanism, and the methylation-induced silencing of ASC has been observed in several types of tumors. NaBu induces cell cycle arrest, markers of cell differentiation and apoptosis in colon cancer. NaBu promotes transcriptional activation by relaxing the DNA conformation and displays anti-proliferative and differentiating activity in a wide variety of cancers. Thus, we used NaBu to investigate the relationship between the status of cell proliferation and the re-expression of ASC in colon carcinoma LS174T cells. Our experiments determined ASC re-expression at the protein level using western blotting. In addition, we used reverse transcriptionpolymerase chain reaction to detect the expression levels of ASC mRNA and an MTT assay to detect the inhibitory rate of cell growth. The apoptosis rate was also detected for further validation of the re-expression of ASC. The results showed that ASC re-expression was significantly increased in the LS174 cells following NaBu treatment in a time-and dose-dependent manner. The expression of ASC also induced the apoptosis of LS174T cells. These results suggest that NaBu plays a role in the reactivation of ASC expression and that the latter promotes the apoptosis of LS174T cells.

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Section: Discussionmentioning

confidence: 99%

Sodium butyrate restores ASC expression and induces apoptosis in LS174T cells

Zhang

Bai

Ren

et al. 2012

International Journal of Molecular Medicine

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“…Importantly, the critical role of p21 induction for mediating HDACi-induced growth arrest in colon cancer cells is demonstrated by the attenuated growth inhibitory effect of HDACi on p21 deficient HCT116 cells. 70 In addition to p21, HDACi also induce expression of several other growth inhibitory proteins including p15INK4b, 92 p16 86 and GADD45α and β 93 Notably, HDACi also downregulate expression of several pro-proliferative genes including c-myc, 94,95 cyclin B1 96 and cyclin D1 97 in colon cancer cells. In contrast to p21 however, the relative importance of these effects in mediating HDACi-induced growth arrest, have not been directly tested.…”

Section: Growth Arrestmentioning

confidence: 99%

HDACs and HDAC inhibitors in colon cancer

Mariadason¹

2008

Epigenetics

192

190

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“…[4][5][6] NaB-mediated cell cycle withdrawal of CRCs appears to be dependent on acetylation of histones and consequent changes in transcription, requiring continuous protein synthesis and the expression of p21. 7 It has recently been shown that 1 mM NaB is the best working concentration to activate the differentiation program in CRCs without triggering apoptosis, whereas 5 mM NaB is sufficient to induce a p53-independent apoptotic cell death by activating a pathway involving p38, PPARg and caspases. 6,8 Several intracellular signaling cascades have been implicated in the regulation of the proliferation-differentiation balance in enterocytes by the coordinated expression of the genome in response to environmental cues.…”

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A novel cell type-specific role of p38α in the control of autophagy and cell death in colorectal cancer cells

et al. 2006

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Cancer develops when molecular pathways that control the fine balance between proliferation, differentiation, autophagy and cell death undergo genetic deregulation. The prospects for further substantial advances in the management of colorectal cancer reside in a systematic genetic and functional dissection of these pathways in tumor cells. In an effort to evaluate the impact of p38 signaling on colorectal cancer cell fate, we treated HT29, Caco2, Hct116, LS174T and SW480 cell lines with the inhibitor SB202190 specific for p38a/b kinases. We report that p38a is required for colorectal cancer cell homeostasis as the inhibition of its kinase function by pharmacological blockade or genetic inactivation causes cell cycle arrest, autophagy and cell death in a cell type-specific manner. Deficiency of p38a activity induces a tissue-restricted upregulation of the GABARAP gene, an essential component of autophagic vacuoles and autophagosomes, whereas simultaneous inhibition of autophagy significantly increases cell death by triggering apoptosis. These data identify p38a as a central mediator of colorectal cancer cell homeostasis and establish a rationale for the evaluation of the pharmacological manipulation of the p38a pathway in the treatment of colorectal cancer. Colorectal cancer is a major health concern, with more than 1 000 000 new cases and 500 000 deaths expected worldwide per year.1 Prognostic evaluation is currently based on histological appearance, and there are no molecular markers internationally recognized as standard predictor factors. The conventional therapy involving surgery and adjuvant therapy seems to give rise to improvements in progression-free and overall survival. Nevertheless about 50% of patients die within 5 years owing to metastasis or recurrent disease.2 The prospects for further substantial advances in the management of colorectal cancer reside in a systematic genetic and functional dissection of cell cycle and cell death regulatory pathways in tumor cells in order to identify differential cellular effects of agents that may have a direct impact on cancer therapy.During the last decade, a number of deacetylase inhibitors (DI) have been identified. These DI induce tumor cells to undergo growth arrest, differentiation, and/or apoptosis in culture and in animal models, at doses that seem to be nontoxic and appear to be selective. Butyrate, a DI that is naturally formed in the human colon, is able to reduce the size and the number of tumors in rat models of bowel cancer.3 In vitro, sodium butyrate (NaB) is a potent differentiating agent for several colorectal cancer cell lines (CRCs).4-6 NaB-mediated cell cycle withdrawal of CRCs appears to be dependent on acetylation of histones and consequent changes in transcription, requiring continuous protein synthesis and the expression of p21. 7 It has recently been shown that 1 mM NaB is the best working concentration to activate the differentiation program in CRCs without triggering apoptosis, whereas 5 mM NaB is sufficient to induce a p53-independent...

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The histone deacetylase inhibitor butyrate downregulates cyclin B₁gene expression via a p21/WAF-1-dependent mechanism in human colon cancer cells

Cited by 59 publications

References 44 publications

Sodium butyrate restores ASC expression and induces apoptosis in LS174T cells

Sodium butyrate restores ASC expression and induces apoptosis in LS174T cells

HDACs and HDAC inhibitors in colon cancer

A novel cell type-specific role of p38α in the control of autophagy and cell death in colorectal cancer cells

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The histone deacetylase inhibitor butyrate downregulates cyclin B1gene expression via a p21/WAF-1-dependent mechanism in human colon cancer cells

Cited by 59 publications

References 44 publications

Sodium butyrate restores ASC expression and induces apoptosis in LS174T cells

Sodium butyrate restores ASC expression and induces apoptosis in LS174T cells

HDACs and HDAC inhibitors in colon cancer

A novel cell type-specific role of p38α in the control of autophagy and cell death in colorectal cancer cells

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Product

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The histone deacetylase inhibitor butyrate downregulates cyclin B₁gene expression via a p21/WAF-1-dependent mechanism in human colon cancer cells