Effect Of Sodium Butyrate Research Articles

The Influence of sodium butyrate on growth curve of bladder cancer cell and cell cycle

Objective To investigate the effect of sodium butyrate on growth of bladder cancer cells. Methods Make a comparison among the growth curve changes of BIU-87 cell and E-J cell of blad-der cancer after the interference of sodium butyrate with different concentrations by applying ~3H-TdR incor-poration test, and adopt flow cytometry to conduct a research on the influence of sodium butyrate on the cell cycle of bladder cancer. Results 1 mmol/L concentration group hasn't shown the restraint on BIU-87 cell and E-J cell in each observation time spots;the 5mmol/L and 10 mmol/L concentration groups have shown obvious growth restraint and the difference is significant (P<0.01); along with the rising sodium butyrate concentration,more and more BIU-87 cells and E-J cells are blocked in G_0/G_1 phrase. Conclu-sion The sodium butyrate restrain the growth of bladder cancer cells with concentration and time depend-ence,which is achieved through the cell cycle blockade in G_0/G_1 phrase. Key words: Bladder carcinoma; Sodium butyrate; Cell cycle

Effects of sodium butyrate on hCTLA4Ig production by CHO cells

Effects of sodium butyrate on hCTLA4Ig production by CHO cells

The Effect of Sodium Butyrate on the Binding of Androgen Receptor Coregulators in Prostate Cancer Cells

The Effect of Sodium Butyrate on the Binding of Androgen Receptor Coregulators in Prostate Cancer Cells

Effects of Sodium Butyrate on Cell Death Induced by Photodynamic Therapy in U373‐MG and D54‐MG Astrocytoma Cell Lines

The damage induced by end products of photodynamic therapy (PDT) in astrocytoma tumors leads to cytotoxicity and cell death. Chromatin modifiers such as sodium butyrate (NaB) induce several genes involved in apoptosis, among others. The PDT improvement was evaluated by the measurement of its effectiveness in the treatment of U373-MG and D54-MG astrocytoma cell lines exposed to NaB. Cells exposed to 80 microg mL(-1) of delta-aminolevulinic acid (ALA) as precursor of endogenous photosensitizer (PS), protoporphyrin IX (PpIX), induced 16.67% and 28.9% of mortality in U373-MG and D54-MG, respectively. The mortality increased to 70.62% and 96.7%, respectively, when U373-MG and D54-MG cells were exposed for 24 h to 8 mm NaB prior to ALA-induction. In this condition, re-expression of some genes related to apoptosis in U373-MG, and differentiation in D54-MG were induced. PpIX accumulation was higher than ALA-induction and the acetylation of histone H4 induced by NaB was verified by immunocytochemistry in both cells. It can be concluded that modified chromatin and genes induced by NaB increment the cellular death induced by PDT in astrocytoma cells using PpIX as endogenous PS.

Effect of sodium butyrate on lung vascular TNFSF15 (TL1A) expression: Differential expression patterns in pulmonary artery and microvascular endothelial cells

Vascular endothelial growth inhibitor TNFSF15 ( TL1A), a ligand for TNFRSF25 ( DR3) and decoy receptor TNFRSF6B ( DcR3), is expressed in human pulmonary arterial (HPAEC) and lung microvascular (HMVEC) endothelial cells where it might modulate inflammation and sickle vasculopathy. Pulmonary disease, endothelial abnormalities and inflammation are prominent features of sickle cell disease (SCD). Butyrate has opposing effects on endogenous TNFSF15 expression in pulmonary endothelium, acting as an inhibitor in HPAEC and an inducer in HMVEC. Similar effects were observed with a known cytokine TNF-α in these two cell types. Furthermore the TNFSF15 promoter utilized different combinations of cis-elements for its expression in these two cell types. AP1-like and G-rich sequence elements were critical for promoter activity in large vessel HPAEC while AP1-like and NF-κB consensus sequence elements were required in small vessel HMVEC. The requirement of an NF-κB sequence element by the TNFSF15 promoter in HMVEC but not in HPAEC supported the notion that HMVEC might be a target of inflammation and vasoocclusion in SCD. The dual effects of butyrate-dependant TNFSF15 regulation in lung endothelium may help in identify inflammatory pathways and understand the role of HMVEC in pathogenesis of vasoocclusion in SCD.

Sodium butyrate induces apoptosis and regulates caspase-3 in colorectal cancer cells COLO205

AIM:To observe the regulatory effects of sodium butyrate on caspase-3 in COLO205 colorectal cancer cells,and to investigate the mechanisms of apoptosis in COLO205 induced by sodium butyrate. METHODS:1,2,4 mmol/L sodium butyrate were co-cultured with COLO205 cells for 48 h,respectively;the viability of COLO205 was detected using MTT method;the expression of caspase-3,using immunohistochemical method;the rate of apoptosis in COLO205,using flow cytometry. RESULTS:Compared with negative control group,the viability of COLO205(0.47 ± 0.09,0.40 ± 0.03,0.37 ± 0.02 vs 0.55 ± 0.09,P 0.05 or 0.01) was lower obviously;sodium butyrate promoted the masculine expression of caspase-3(31.9 ± 1.15,40.6 ± 1.04,51.7 ± 1.17 vs 29.4 ± 1.02,P 0.05or 0.01) ,and elevated the rate of apoptosis(8.27% ±0.42%,15.1% ± 0.72%,21.6% ± 0.95% vs 7.0% ± 0.33%,P 0.05 or 0.01) in COLO205. CONCLUSION:Sodium butyrate induces the apoptosis of COLO205 through enhancing the expression of caspase-3 gene.

Evidence for Insertional RNA Editing in Humans

Large-scale analysis directly at the protein level holds the promise of uncovering features not apparent or present at the gene level [1-3]. Although mass spectrometry (MS)-based proteomics can now identify and quantify thousands of cellular proteins in large-scale proteomics experiments, much of the peptide information contained in these experiments remains unassigned [4]. Here, we use such information to discover a previously unreported mechanism creating altered protein forms. Linker histones H1 and high-mobility group (HMG) proteins are abundant nuclear proteins that regulate gene expression through modulation of chromatin structure [5-8]. In the high-resolution MS analysis of histone H1 and HMG protein fractions isolated from human cells, we discovered peptides that mapped upstream of the known translation start sites of these genes. No alternative upstream start site exists in the genome, but analysis of Expressed Sequence Tag (EST) databases revealed that these N-terminally extended (ET) proteins are due to in-frame translation of the 5' untranslated region (5'UTR) sequences of the transcripts. The new translation start sites are created by a single uridine insertion between AG, reflecting a previously unreported RNA-editing mechanism. To our knowledge, this is the first report of RNA-insertion editing in humans and may be an example of the type of discoveries possible with modern proteomics methods.

The effects of sodium butyrate, an inhibitor of histone deacetylase, on the cocaine- and sucrose-maintained self-administration in rats

In order to substantiate the concept that cocaine behavioral effects may be influenced by histone modification, rats were trained to self-administer cocaine intravenously (0.75 mg/(kginjection)), and were systemically pretreated with sodium butyrate (NaBu), a potent histone deacetylase inhibitor, before the test session during the maintenance phase. The effect of NaBu on a control reinforcer (sucrose)-induced self-administration was also assessed. NaBu (100-200 mg/kg) was inactive in altering the cocaine (0.75 mg/(kg injection))-maintained responding and at the highest dose (400 mg/kg) it did increase cocaine-induced lever presses during the maintenance phase. On the other hand, sucrose-reinforcing potential was not altered when NaBu was given at the highest dose (400 mg/kg). These findings extend previous observations that changes in histone acetylation are relevant to cocaine-induced behavioral effects. Given that histone acetylase inhibitor enhances cocaine-induced behavioral plasticity, the therapeutic benefits of histone acetyltransferase inhibitors warrant further investigation in the experimental models of cocaine abuse.

QS166. Engineering Endothelial Cell Resistance to Flow Induced Detachment

Introduction: We have previously demonstrated that high shear stress induces apoptosis dependent detachment of human aortic endothelial cells (HAEC) from Dacron. We tested the hypothesis that pre-treatment with sodium butyrate would render HAEC resistant to flow induced detachment. The effects of sodium butyrate on HAEC are undefined, however in a variety of different cells, it impacts cell cycle, cytoskeletal architecture, and cell shape. Methods: HAEC were cultured in the presence or absence of sodium butyrate (2 mM) in medium for 4 days, then seeded onto Dacron membranes.

Effect of sodium butyrate on growth performance and response to lipopolysaccharide in weanling pigs1

Two experiments were conducted to determine the effects of dietary sodium butyrate on growth performance and response to Escherichia coli lipopolysaccharide (LPS) in weanling pigs. In a 28-d experiment, 180 pigs (initial BW 6.3 kg) were fed 0, 0.05, 0.1, 0.2, or 0.4% sodium butyrate, or 110 mg/kg of dietary tylosin. There was no effect of dietary sodium butyrate or tylosin on overall G:F, but there was a linear trend (P < 0.07) toward decreased ADFI and ADG as levels of sodium butyrate increased. In a second 28-d experiment, 108 pigs (initial BW 6.3 kg) were assigned to 1 of 3 dietary treatments: 1) no antibiotics, 2) 0.2% sodium butyrate, or 3) 55 mg/kg of carbadox. On d 14, a subset of pigs from the no-antibiotic and butyrate treatment groups was challenged with E. coli LPS or injected with sterile saline in a 2 x 2 factorial arrangement (+/-LPS challenge; +/-dietary butyrate; n = 6 pigs/treatment group). Four hours after LPS challenge, blood samples were obtained, and samples of LM, liver, and ileum were collected for gene expression analysis. Serum samples were analyzed for IL-6, tumor necrosis factor alpha (TNFalpha), alpha(1)-acid glycoprotein, cortisol, IGF-I, insulin, and metabolites. The relative abundance of tissue cytokine and IGF-I mRNA was measured by real-time PCR. Feeding diets containing sodium butyrate or carbadox did not alter ADG or ADFI compared with pigs fed the control diet. From d 0 to 14, pigs fed diets containing 0.2% sodium butyrate had decreased (P < 0.05) ADG and tended (P < 0.06) to have decreased G:F compared with animals fed diets containing carbadox. Challenge with LPS increased (P < 0.05) serum cytokines and cortisol and decreased (P < 0.05) serum glucose and triglycerides. Injection with LPS increased (P < 0.05) the relative abundance of hepatic IL-6 and TNFalpha mRNA, increased (P < 0.05) LM TNFalpha mRNA content, and decreased (P < 0.05) IGF-I mRNA in LM. For serum cortisol, there was an interaction (P < 0.05) between dietary butyrate and LPS. The increase in serum cortisol attributable to LPS was greater (P < 0.05) in pigs fed butyrate than in pigs fed the control diet. There tended (P < 0.10) to be an interaction between LPS and diet and for butyrate to increase the relative abundance of IL-6 mRNA in LM. Carbadox did not alter cytokine or IGF-I mRNA or serum metabolites, but did decrease (P < 0.05) serum TNFalpha. These data indicate that dietary sodium butyrate does not enhance growth performance, but may regulate the response to inflammatory stimuli in weanling pigs.

Sodium butyrate induced keratinocyte apoptosis

Apoptosis of keratinocytes is a key mechanism required for epidermal homeostasis and the renewal of damaged cells. Its dysregulation has been implicated in many skin diseases including cancer and hyperproliferative disorders. In the present study, the effect of sodium butyrate, a histone deacetylase inhibitor, on keratinocyte apoptosis was investigated using the HaCaT human keratinocyte cell line. Sodium butyrate induced morphological changes associated with apoptosis and nuclear fragmentation of HaCaTs. Annexin V staining demonstrated that sodium butyrate induced apoptosis in a dose and time-dependent manner with 50% of HaCaTs apoptotic after exposure to 0.8 mg/ml sodium butyrate for 24 h. Apoptosis was associated with upregulation of cell surface expression of the death receptor Fas and activation of the extrinsic caspase pathway, with induction of caspase 8 activity peaking after 8 h. Caspase 3 activity peaked after 24 h and was associated with cleavage of the caspase 3 substrate, poly (ADP-ribose) polymerase (PARP). The intrinsic caspase pathway was not activated as caspase 9 activity was not detected, and there was no change in the expression of terminal differentiation markers keratin 10 and involucrin following sodium butyrate treatment. Together these results indicate that sodium butyrate is a potent inducer of Fas associated apoptosis via caspase activation in HaCaT keratinocytes, an effect that is independent of the induction of terminal differentiation.

Effect of sodium butyrate on doxorubicin resistance and expression of multidrug resistance genes in thyroid carcinoma cells

ATP-binding cassette (ABC) transporters [P-glycoprotein and multidrug resistance (MDR)-associated proteins (MRPs)] confer MDR to tumor cells. In this work, we investigated doxorubicin resistance in three thyroid carcinoma cell lines. The effects of sodium butyrate (NaB) on doxorubicin-induced cytotoxicity and on transcription of three MDR genes were also studied. Thyroid cell lines established from anaplastic (8505C) and two poorly differentiated follicular (FTC 238 and FTC 133) cancers were cultured for 24 or 48 h in the presence of NaB (0, 0.25, 0.5 and 1 mM) alone or combined with increased doses of doxorubicin. Cytotoxicity was assessed using the MTT test. MDR1, MRP1 and MRP2 mRNA expression was studied by RT-PCR. After a 24- or 48-h incubation, doxorubicin alone induced cytotoxicity in the three cell lines. NaB significantly (p<0.0001) increased the doxorubicin-induced cytotoxicity. MRP1 transcripts were expressed in the three non-treated cell lines. MDR1 and MRP2 mRNAs were both present in 8505C, but absent in FTC 133 or FTC 238 cell lines, respectively. Treatment with NaB for 24 or 48 h induced no change in MRP1 and MRP2 levels, but increased MDR1 expression in 8505C and FTC 238 cell lines comparably to alkaline phosphatase activity. In conclusion, MRP1 and sometimes MDR1 and MRP2 are expressed in the tested cell lines. NaB potentiates doxorubicin-induced cytotoxicity independently of the ABC transporters. The combination of doxorubicin and NaB might have clinical implications for thyroid cancer therapy.

The effect of sodium butyrate in combination with ATRA on the proliferation/differentiation of SKM-1.

To explore the molecular mechanisms of sodium butyrate working on SKM-1 cell proliferation/differentiation and to study its synergistic effect with all-trans retinoic acid (ATRA), SKM-1 cells were grown in the absence or presence of sodium butyrate and/or ATRA. The percentage of viable cells was determined by trypan blue exclusion. Differentiation was determined by nitroblue tetrazolium (NBT) reduction and cell surface adhesion molecules was analyzed by FACS. Cell cycle distribution was examined after DNA staining by propidium iodide. D-type cyclins, cdks and P21 mRNA were studied by reverse transcription-polymerase chain reaction. Our results showed that sodiun butyrate and/or ATRA blocked cells mainly in the G0/G1 phase of the cell cycle. ATRA inhibited the mRNA expression of CDK6, CDK4, cyclinD3 and cyclinD1. Sodium butyrate inhibited the mRNA expression of CDK2, cyclinD2 and cyclinD1. ATRA and sodium butyrate inhibited the mRNA expression of CDK6, CDK4, CDK2, cyclinD1, cyclinD2 and cyclinD3. Both ATRA and/or sodium butyrate stimulated p21 expression at the mRNA levels. Our results suggest that the effect of sodium butyrate on cell proliferation/differentiation might be linked to its ability to induce expression of p21 mRNA and inhibit the cyclin-cdk complexes. Our observations support the notion that the sodium butyrate works synergistically with ATRA.

P14 Polyunsaturated fatty acids sensitise colon cancer cells to the apoptotic effects of sodium butyrate

P14 Polyunsaturated fatty acids sensitise colon cancer cells to the apoptotic effects of sodium butyrate

Butyrate inhibits pancreatic cancer invasion.

Pancreatic cancer is the most deadly gastrointestinal malignancy because of its propensity for local invasion and early metastasis. Integrin chains, in particular beta4, can promote invasion in other cancers. The effect of sodium butyrate (NaBT), which induces differentiation in transformed cells, on integrin expression is unknown. The purpose of this study was to determine patterns of integrin expression in pancreatic cancer cells and investigate the effect of NaBT on integrin expression and invasion. Integrin expression was assessed in the less invasive MIA-PaCa-2 and PANC-1 and more invasive L3.6, AsPC-1, and SUIT-2 human pancreatic cancer cell lines by ribonuclease (RNase) protection assay. Western blotting and immunofluorescent staining for beta4 expression was determined after NaBT treatment. Matrigel invasion chambers were used to assess pancreatic cancer cell invasion. beta4 and beta7 integrin expression was highest in L3.6, AsPC-1, and SUIT-2 cells. NaBT reduced the expression of beta4 integrin in AsPC-1 cells including less cell surface beta4. Invasion of AsPC-1 cells was also reduced by NaBT. Expression of beta4 is higher in more aggressive pancreatic cancer cells; NaBT inhibits beta4 expression and invasion. NaBT may represent a novel strategy to inhibit pancreatic cancer invasion and improve the prognosis of this deadly disease.

Effect of sodium butyrate on the expression of cathepsins D

Effect of sodium butyrate on the expression of cathepsins D

Effect of sodium butyrate combined with chuanhuning on HCT-8 cell line proliferation

Effect of sodium butyrate combined with chuanhuning on HCT-8 cell line proliferation

Sodium Butyrate Inhibits Cell Growth and Stimulates p21WAF1/CIP1 Protein in Human Colonic Adenocarcinoma Cells Independently of p53 Status

Butyric acid, one of the short-chain fatty acids produced by microbial fermentation in the colon, exhibits antiproliferative activities in various cancer cell lines. The initial objective of the study was to assess whether the effect of sodium butyrate (NaB) on cell growth differed by p53 status of the cells. Four human colorectal adenocarcinoma cell lines were used: HT29 (p53 point mutation), Caco2 (p53 truncation), LS513 (p53 wild type), and Lovo (p53 wild type). NaB significantly inhibited cell growth in all four cell lines. NaB arrested HT29 and LS513 cells in G0/G1 and Caco2 and Lovo in G2-phase. A second objective was to determine whether NaB similarly affected the cyclin-dependent kinase inhibitor, p21WAF1/CIP1. In all cell lines, p21 mRNA levels were immediately elevated after NaBexposure, and p21 protein levels were increased within 6 h. NaB increased p21 promoter activity in both Caco2 and Lovo, suggesting p53 independence. NaB did not influence p21 mRNA stability. Although three DNase I hypersensitivity sites were identified in the region of the p21 gene, induction of p21mRNAbyNaBwas not accompanied by relaxation of the chromatin in the region of the p21 gene.

Selective repression of c- fos gene transcription in rat embryo fibroblasts transformed by oncogenes E1A and cHa-ras

Transformation of REF cells by oncogenes E1A and c Ha-ras leads to activation of AP-1 factor concomitantly with down-regulation of c- fos gene transcription. Here we addressed two issues: (i) how does transcription of Fos/Jun-regulated genes change in the cells lacking Fos-Jun heterodimers; (ii) to which extent HDAC-mediated chromatin reorganization does affect, apart from c- fos, transcription of some other early and late-response genes. To this end, we studied the kinetics of serum-stimulated transcription of c- fos, c- jun, fra-1, egr-1, and cyclinD1 genes, as well as the effects of sodium butyrate, an inhibitor of histone deacetylase activity, on transcription of these genes in normal REF cells and transformants E1A + ras.

Aberrant regulation of human intestinal proglucagon gene expression in the NCI-H716 cell line.

Despite interest in understanding glucagon-like peptide-1 (GLP-1) production, the factors important for GLP-1 biosynthesis remain poorly understood. We examined control of human proglucagon gene expression in NCI-H716 cells, a cell line that secretes GLP-1 in a regulated manner. Insulin, phorbol myristate acetate, or forskolin, known regulators of rodent proglucagon gene expression, had no effect, whereas sodium butyrate decreased levels of NCI-H716 proglucagon mRNA transcripts. The inhibitory effect of sodium butyrate was mimicked by trichostatin A but was not detected with sodium acetate or isobutyrate. The actions of butyrate were not diminished by the ERK1/2 inhibitor PD98059, p38 inhibitor SB203580, or soluble guanylate cyclase inhibitor LY83583 or following treatment of cells with KT5823, a selective inhibitor of cGMP-dependent protein kinase. NCI-H716 cells expressed multiple proglucagon gene transcription factors including isl-1, pax-6, pax-2, cdx-2/3, pax-4, hepatocyte nuclear factor (HNF)-3 alpha, HNF-3beta, HNF-3 gamma, and Nkx2.2. Nevertheless, the butyrate-dependent inhibition of proglucagon gene expression was not associated with coordinate changes in transcription factor expression and both the human and rat transfected proglucagon promoters were transcriptionally inactive in NCI-H716 cells. Hence, NCI-H716 cells may not be a physiologically optimal model for studies of human enteroendocrine proglucagon gene transcription.