Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “BUTYRATES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 613 records · Page 34Linked to original sources
PubMed1994

An interleukin 2/sodium butyrate combination as immunotherapy for rat colon cancer peritoneal carcinomatosis.

BACKGROUND/AIMS: Immunotherapy using interleukin 2 has had disappointing results in the treatment of colon cancer. Overcoming escape mechanisms, such as lack of antigen presentation and absence of accessory adhesion molecules on cancer cells, may increase its efficiency. We tried to do so by modifying the phenotype of the weakly immunogenic rat colon cancer PROb cells with sodium butyrate. METHODS: After in vitro treatment with butyrate, PROb cells were tested for lymphokine-activated killer cell sensitivity and, using cytofluorometry, expression of adhesion molecules. We then treated established PROb peritoneal carcinomatoses with intraperitoneal injections of interleukin 2 and butyrate. Tumors were studied histologically and immunohistochemically. We tested the specificity of the immune protection by subsequent subcutaneous challenges with either PROb or glioma cells and by Winn's assay. RESULTS: Butyrate increased lymphokine-activated killer cell sensitivity and expression of major histocompatibility complex class I and intercellular adhesion molecule 1 in vitro. Interleukin 2/butyrate combination resulted in cases of complete cure of carcinomatosis with specific protection against PROb cells. We noticed a complex stroma reaction with numerous functional antigen presenting cells close to PROb cells. CONCLUSIONS: The complete regression of tumor masses may be attributed, at least in part, to a butyrate-induced increase in immunogenicity of the cancer cells. This new combined immunotherapy may be of interest in the treatment of colon cancer.

Adenocarcinoma↗
PubMed1995

Immunization against a rat colon carcinoma by sodium butyrate-treated cells but not by interleukin 2-secreting cells.

BACKGROUND & AIMS: Vaccination of patients with colon cancer with irradiated autologous tumor cells and bacille Calmette-Guérin (BCG) was reported to augment mean survival. It was recently observed that a local treatment combining recombinant interleukin 2 and the differentiation agent sodium butyrate cured rats with colon cancer peritoneal carcinomatosis. To optimize vaccination protocols, the comparison of the efficacy of irradiated tumor cells mixed with BCG with that of interleukin 2-gene-transfected cells and of tumor cells pretreated with sodium butyrate was performed. METHODS: The poorly immunogenic rat colon carcinoma cells PROb were used in a vaccination assay. Interleukin 2-transfected PROb cells, either proliferating or irradiated, were used. The efficiency of irradiated PROb cells mixed with BCG, of interleukin 2-transfected cells, or of cells pretreated with sodium butyrate was tested. RESULTS: Vaccination with irradiated parental cells and BCG did not provide protection. Irradiated interleukin 2-transfected cells were poorly efficient in the vaccination assay. Conversely, vaccination with irradiated parental cells pretreated with sodium butyrate before injection provided good protection. CONCLUSIONS: Interleukin 2-secreting cells efficiently vaccinated animals when injected while replicating but not after irradiation. Conversely, sodium butyrate pretreatment provided a simple and efficient vaccination scheme that generated a long-term immune memory and allowed the use of irradiated cells.

Animals↗
PubMed1985

Effects of butyric acid on cell cycle regulation and induction of histone H1(0) in mouse cells and tissue culture. Inducibility of H1 (0)in the late S-G2 phase of the cell cycle.

We have examined the regulation of the synthesis of histone H1(0) in cultured mammalian cells treated with butyric acid. Treatment of cells with the inducer results in the arrest of synthesis of DNA and the other histones, while increasing the synthesis of H1(0) by a factor of 11. The induction of H1(0) by butyric acid occurs in a pulse with a peak at six hours, followed by a decrease to negligible levels. This pulse-like induction appears to be due to the fact that the cells are inducible for H1(0) only in the late S or G2 phases of the cell cycle. This, coupled with the fact that butyric acid blocks cells in G1, results in the burst of H1(0) synthesis after addition of the inducer. The G1 block provoked by butyric acid does not appear to result from the accumulation of H1(0). Removal of butyric acid from G1-blocked cells resulted in the resumption of cellular proliferation without prior loss of H1(0), demonstrating that the presence of this histone is not sufficient to prevent cellular proliferation.

Animals↗
PubMed1990

Urinary organic acid profiles in fatty Zucker rats: indications for impaired oxidation of butyrate and hexanoate.

The urinary excretion of 45 organic acids, monitored by gas-liquid chromatography, was compared in fatty (fa/fa) and lean (Fa/?) Zucker rats maintained on a chemically simplified diet. At the age of 6, 16, and 22 weeks, fatty rats excreted more of the various organic acids than their lean counterparts. However, the greatest difference was in the excretion of ethylmalonate, even when excretion data were normalized to body weight. The next highest excretion difference was in adipate and an unknown compound, and the third highest in pyruvate. A second group of rats examined at 7 weeks also excreted an excess of these four acids, as well as glucuronate and indole-3-acetate. The excessive excretion of ethylmalonate and adipate, which is characteristic of human genetic defects in short- and medium-chain fatty acid oxidation, suggested that the oxidation of butyrate and hexanoate might be impaired in the fatty rat. Thus, as a test of their capacity to oxidize medium- and short-chain fatty acids, two groups of fatty and lean rats were transferred to diets enriched with either trioctanoylglyceride, a medium-chain triglyceride (MCT), or sodium butyrate, a short-chain fatty acid. Both lean and fatty rats on the MCT diet, but only the lean rats on the butyrate-enriched diet, increased their excretion of adipate. However, on both the MCT and butyrate diet, ethylmalonate excretion increased only in lean rats, almost reaching amounts found previously in fatty rats. These results suggest that the fatty rat has an impairment of the beta-oxidation of butyrate and hexanoate, a defect that might increase intracellular concentrations of butyryl-CoA, the optimal primer for the synthesis of long-chain fatty acids.

Acids↗
PubMed1985

Effects of pre-treatment with sodium butyrate on the frequencies of X-ray-induced chromosomal aberrations in human peripheral blood lymphocytes.

The effects of sodium butyrate-mediated alterations in chromatin structure on the yields of X-ray-induced chromosomal aberrations were studied in human peripheral blood lymphocytes. Unstimulated (G0) lymphocytes were pre-treated with sodium butyrate (5 mM) for 24 h, X-irradiated and then stimulated to pass through the cell cycle. Cells in their first post-radiation metaphase were scored for chromosomal aberrations. In parallel biochemical experiments nucleoid sedimentation technique was used to examine the induction and repair of DNA-strand breaks. The results show that sodium butyrate pre-treatment leads to a significant increase in the frequencies of dicentrics and rings, but not of fragments. The data from biochemical studies suggest that the numbers and rates of repair of X-ray-induced DNA-strand breaks are the same in butyrate-treated and untreated cells. We therefore suggest that the observed effect is probably a consequence of butyrate-induced conformational changes in the chromatin of G0 lymphocytes.

Butyrates↗
PubMed1982

The effect of sodium butyrate on acetylation in vitro of chromosomal proteins in three classes of liver nuclei from different ages of rats.

The optimum conditions of in vitro incorporation of sodium [3H]acetate into sliced rat liver were studied. The incubations with sliced liver from three different ages of rats were performed in the presence of sodium n-butyrate. It was found that butyrate decreases the incorporation of sodium [3H]acetate into the homogenate, isolated nuclei, non-histone chromosomal proteins and histones for all age groups. The acetylations of non-histone chromosomal proteins and histones increase with age upto 2-months and decrease in 4-month-old rats both in the absence and presence of butyrate. Liver nuclei were fractionated by the simple method of zonal centrifugation into three classes, namely diploid stromal, diploid parenchymal and tetraploid parenchymal nuclei. The acetylations of non-histone chromosomal proteins and histones in three classes of nuclei of three ages of rats were studied in the presence and absence of butyrate. Butyrate can decrease the overall acetylations of non-histone chromosomal proteins and histones but increase the amount of polyacetylated histone H4 in all classes of nuclei of the three ages.

Acetates↗
PubMed1984

Effects of sodium butyrate and dimethylsulfoxide on human pancreatic tumor cell lines.

The effects of 1 mM sodium butyrate or 2% dimethylsulfoxide (DMSO) on three human pancreatic tumor cell lines were examined. The cell lines tested were MIA PaCa-2, PANC-1 and CAPAN-1. Both butyrate and DMSO inhibited the ability of all three lines to form colonies in soft agar. These results suggest that the use of these agents provides a model system for the study of the molecular changes involved in human pancreatic cancer. In butyrate all the cell lines showed a marked increase in cellular levels of alkaline phosphatase, while growth in DMSO led to a reduction in most cases. DMSO caused a rapid reduction in the attachment of all three cell lines to collagen substrates, while butyrate had no effect. These results illustrate the fact that although both butyrate and DMSO appear to greatly reduce the parameters correlated with tumorigenicity of human pancreatic cancer cells, the mechanisms involved may be very different.

Agar↗
PubMed1991

Effect of sodium butyrate on metallothionein induction and cadmium cytotoxicity in ROS 17/2.8 cells.

ROS 17/2.8 cells, a cloned rat osteosarcoma cell line, are exceptionally sensitive to the cytotoxic effects of cadmium. This sensitivity is associated with the inability of this metal to induce the synthesis of metallothionein, a transition metal-binding protein, which detoxifies this metal by its sequestration. Sodium butyrate induces the synthesis of metallothionein in these cells in a concentration-dependent manner. Treatment with this agent also significantly increases the resistance of these cells to the cytotoxic effects of cadmium and the protective effect of butyrate is reversed upon its removal from culture medium. Butyrate treatment did not significantly alter the accumulation of cadmium by these cells. Hence, the increased synthesis of metallothionein in butyrate-treated cells is not due to increased cellular uptake of cadmium. Inhibition of DNA synthesis due to butyrate was not a sufficient condition to alter metallothionein synthesis or to protect against Cd-induced cytotoxicity. Equivalent inhibition of DNA synthesis with hydroxyurea failed to increase metallothionein synthesis in cadmium-treated cells. These results indicate that modulation of metallothionein gene expression in this cell line is the critical factor in determining cellular sensitivity to the cytotoxic effects of cadmium.

Animals↗
PubMed1991

Novobiocin modulates cytokeratin assembly and differentiation of human hepatoma cells induced by butyrate and teleocidin.

A differentiation inducer butyrate and a tumor promoter teleocidin had inhibitory effects on the proliferation of PLC/PRF/5 hepatoma. Both of these reagents stimulated the production of procollagen type III peptide, enhanced the cytokeratin assembly and altered the morphological appearance. Novobiocin, a topoisomerase II inhibitor, enhanced the cytokeratin assembly induced by butyrate but antagonized that induced by teleocidin without changing the expression and the phosphorylation state of cytokeratin proteins. In addition, novobiocin acted synergistically with butyrate but not with teleocidin in stimulating the procollagen production and the acetate uptake. These results suggest that butyrate and teleocidin induce cell differentiation via distinct signaling pathway and that novobiocin and butyrate can be used as subsidiary drugs in preventing the growth of hepatoma.

Acetylation↗
PubMed1987

Stimulation of DNA synthesis in primary cultures of adult rat hepatocytes by sodium butyrate.

Replicative DNA synthesis in primary cultures of adult rat hepatocytes is increased by the addition of the histone deacetylase inhibitors, propionate or butyrate. DNA synthesis was increased by the addition of 0.5 or 1.0 mM butyrate; in contrast 5.0 mM butyrate inhibited replicative DNA synthesis. Replicative DNA synthesis was increased only when low levels of butyrate were added as the hepatocytes entered the S phase. The observed apparent increase in replicative DNA synthesis was real, and not owing to changes in the specific activity of the dTTP precursor pool. The effects of butyrate and propionate on DNA synthesis appear to be related to their effects on histone acetylation.

Acetylation↗
PubMed1997

Acetate and propionate potentiate the antiproliferative effect of butyrate on RBL-2H3 growth.

1. The effect of acetate, propionate, and butyrate separately and combined on RBL-2H3 (a rat basophilic leukemic cell type) proliferation during 24, 48, and 72 hr was examined. Also, the effect of a mixture of the three volatile fatty acids on proliferation of HeLa-155 (a human adenocarcinoma), C57 B1/6J (a mouse melanoma), and MCF-7 (human breast tumor) during 8 days was investigated. 2. Acetate and propionate per se did not present any effect on RBL-2H3 growth during 72 hr, however, when acetate and propionate were added together a significant inhibition of this cell growth was found; 18% for 48 and 37% for 72 hr. The addition of butyrate to the culture medium caused a 75% decrease in the rate of this cell growth either after 48 and 72 hr. This effect of butyrate was pronounced by acetate (86% and 90% for 48 and 72 hr, respectively), propionate (87% for 48 and 93% for 72 hr), and acetate and propionate together (76% for 48 and 92% for 72 hr). 3. Daily addition of a mixture of the short-chain fatty acids (10 mM acetate, 2 mM propionate and 1.5 mM butyrate) markedly decreased the number of cells after 8 days: 58% for RBL-2H3, 42% for HeLa-155, 91% for C57 B1/6J and 55% for MCF-7. 4. These results support the proposition that a fiber-rich diet that leads to great production of butyrate but also of propionate and acetate would be more effective to prevent the occurrence of colorectal cancer than the administration of this short-chain fatty acid given alone.

Acetates↗
PubMedDate not supplied

Effects of sodium butyrate on X-ray and bleomycin-induced chromosome aberrations in human peripheral blood lymphocytes.

Peripheral blood lymphocytes from normal human volunteers or from Down syndrome patients were pre-treated with sodium butyrate (a compound which is known to induce structural modifications in the chromatin through hyperacetylation of nucleosomal core histones) and exposed to X-irradiation or treated with bleomycin in vitro in the G0 and/or G1 stage(s) of the cell cycle. The frequencies of chromosomal aberrations in the first mitosis after treatment were scored. The results show an enhancement in the yield of aberrations in the butyrate pre-treated groups. However, the absolute frequencies of chromosomal aberrations as well as the relative increases with butyrate pre-treatment varied between blood samples from different donors suggesting the existence of inter-individual variations. There is a parallelism between the effects of X-irradiation or of combined treatments in G0 and G1 stages and between effects observed in the X-ray and bleomycin series. The increase in the yields of chromosomal aberrations in butyrate-treated and X-irradiated lymphocytes (relative to those which received X-irradiation alone) is interpreted as a consequence of the inhibition of repair of DNA damage by butyrate.

Bleomycin↗
PubMed1997

Modulation of glutathione level during butyrate-induced differentiation in human colon derived HT-29 cells.

Glutathione plays an important role in various cellular functions including cell growth and differentiation. In the present study, cell differentiation was induced by butyrate in human colon cell line HT-29 and cellular thiol status was assessed. It was observed that butyrate-induced differentiation was associated with decrease in cellular GSH level and this was prominent at early stages of differentiation. Buthionine sulfoximine (BSO), a specific cellular GSH depleting agent, did not induce differentiation in cells but potentiated the differentiation induced by butyrate. Both BSO and butyrate individually and together inhibited cell growth. These studies suggest that cellular GSH level is modulated in butyrate-induced differentiation and decrease of GSH at the initial stage might facilitate cellular differentiation.

Alkaline Phosphatase↗
PubMed1987

Biochemical and ultrastructural alterations accompany the anti-proliferative effect of butyrate on melanoma cells.

The effect of sodium butyrate on mouse and human melanoma cell lines was evaluated. Sodium butyrate (0.1-2mM) is shown to reduce the clonogenic potential of several melanoma cell lines. The antiproliferative effect of sodium butyrate is accompanied by a marked increase in the activity of the plasma-membrane bound enzyme gamma-glutamyl transpeptidase. Sodium butyrate treated cells acquire a well developed rough endoplasmic reticulum and accumulate fat droplets. The development of the endoplasmic reticulum is associated with a marked increase in the activity of the enzyme marker NADPH cytochrome c reductase. It is suggested that the phenotypic alterations induced by sodium butyrate may serve as markers for the action of this agent on melanoma cells and other tumours.

Animals↗
PubMed1993

Identification of sequence elements in mouse calbindin-D28k gene that confer 1,25-dihydroxyvitamin D3- and butyrate-inducible responses.

We have examined the 5' flanking region of the mouse calbindin-D28k gene and identified a 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]-responsive element by deletion mutant analysis of the native promoter as well as by studies with a heterologous thymidine kinase (TK) promoter. The segment between residues -200 and -169 was found to confer a dose-dependent 1,25-(OH)2D3 responsiveness through the TK promoter in Ros 17/2.8 cells as well as in CV-1 cells cotransfected with pAV-hVDR (human vitamin D receptor expression vector). This region contains sequences homologous to the rat osteocalcin vitamin D response element (VDRE). Incubation of this element with nuclear extracts from 1,25-(OH)2D3-treated Ros 17/2.8 cells or from 1,25-(OH)2D3-treated COS cells that had been transfected with pAV-hVDR resulted in a specific protein-DNA interaction. In addition to 1,25-(OH)2D3, sodium butyrate, a differentiating agent, has also been found to modulate expression of calbindin-D28k. Deletion analysis of the mouse calbindin-D28k promoter as well as studies with a heterologous TK promoter resulted in identification of a butyrate-responsive element between -180 and -150 that was found to bind specifically to nuclear factors from butyrate-treated Ros 17/2.8 cells. This butyrate-responsive element may represent a genetic element acted upon by enhancer binding proteins. In summary, the 5' flanking region of the mouse calbindin-D28k gene contains responsive elements that interact with nuclear factors and may mediate, at least in part, the enhanced expression of this gene by 1,25-(OH)2D3 and butyrate.

Animals↗
PubMed1998

p21(WAF1) is required for butyrate-mediated growth inhibition of human colon cancer cells.

A diet high in fiber is associated with a decreased incidence and growth of colon cancers. Butyrate, a four-carbon short-chain fatty acid product of fiber fermentation within the colon, appears to mediate these salutary effects. We sought to determine the molecular mechanism by which butyrate mediates growth inhibition of colonic cancer cells and thereby to elucidate the molecular link between a high-fiber diet and the arrest of colon carcinogenesis. We show that concomitant with growth arrest, butyrate induces p21 mRNA expression in an immediate-early fashion, through transactivation of a promoter cis-element(s) located within 1.4 kb of the transcriptional start site, independent of p53 binding. Studies using the specific histone hyperacetylating agent, trichostatin A, and histone deacetylase 1 indicate that growth arrest and p21 induction occur through a mechanism involving histone hyperacetylation. We show the critical importance of p21 in butyrate-mediated growth arrest by first confirming that stable overexpression of the p21 gene is able to cause growth arrest in the human colon carcinoma cell line, HT-29. Furthermore, using p21-deleted HCT116 human colon carcinoma cells, we provide convincing evidence that p21 is required for growth arrest to occur in response to histone hyperacetylation, but not for serum starvation nor postconfluent growth. Thus, p21 appears to be a critical effector of butyrate-induced growth arrest in colonic cancer cells, and may be an important molecular link between a high-fiber diet and the prevention of colon carcinogenesis.

Butyrates↗
PubMed1998

Butyrate and glucose metabolism in isolated colonocytes in the developing rat colon.

BACKGROUND: The newborn colon is devoid of microflora, in that bacterial colonization is established after birth. Short chain fatty acids, products of bacterial fermentation, are the major energy source for colonocytes. Because it is not known whether colonocytes in the newborn can metabolize butyrate, this was examined in newborn and infant rat colon. METHODS: Isolated colonocytes from rats of different perinatal ages were incubated with 14C-labeled butyrate or glucose in vitro. Complete oxidation was estimated by the production of 14C-labeled carbon dioxide, whereas intermediate metabolites were measured enzymatically. RESULTS: Oxidation of butyrate (in micromoles per hour per milligram of protein) was highest in newborns (5.83+/-1.76), declining to 1.32+/-0.28 at day 10 and to 0.34+/-0.04 in adult rats. Glucose oxidation was also highest at birth (0.39+/-0.23), with a minor increase at approximately day 20 (weaning period) before decreasing to adult levels (0.05+/-0). Butyrate oxidation was substantially higher than was glucose oxidation in all age groups. Production of metabolic intermediates paralleled substrate oxidation. Acetoacetate production was 4.35+/-2.68, 2.07+/-1.29, and 0.27+/-0.09 nmol/hr per milligram of protein in newborns, at postnatal day 10, and in adults, respectively. The corresponding values for beta-hydroxybutyrate were 3.62+/-3.35, 0.2+/-0.07, and 0.09+/-0.03 nmol/hr per milligram of protein; and L-lactate production was 0.54+/-0.52, 0.06+/-0.04, and 0.02+/-0 micromol/hr per milligram of protein respectively. CONCLUSIONS: Neonatal rat colon epithelial cells resemble adult colonocytes in their preference for butyrate as a metabolic substrate, indicating a constitutive expression of this property.

3-Hydroxybutyric Acid↗
PubMed1991

Resistance of Streptomyces cinnamonensis to butyrate and isobutyrate: production and properties of a new anti-isobutyrate (AIB) factor.

Butyrate and isobutyrate (after isomerization to n-butyrate) are specific precursors for the biosynthesis of monensin A in Streptomyces cinnamonensis. High concentrations of both butyrate and isobutyrate (greater than 20 and 10 mM, respectively) were toxic to S. cinnamonensis plated on solid medium. Spontaneous mutants resistant to these substances were isolated. These new strains produced monensins at even higher concentrations of butyrate or isobutyrate, with an increased yield of monensin A. S. cinnamonensis produced an anti-isobutyrate (AIB) factor, which was originally found to be excreted by some isobutyrate-resistant stains growing on solid medium containing isobutyrate. On plates, the AIB factor efficiently counteracted toxic concentrations not only of isobutyrate, but also of acetate, propionate, butyrate, 2-methylbutyrate, valerate and isovalerate against S. cinnamonensis as well as other Streptomyces species. Although the AIB factor enabled normal growth, sporulation and monensin production on plates, it did not have positive effects on submerged cultures of S. cinnamonensis with isobutyrate. The partial purification of the AIB factor was achieved. The role of the AIB factor during spore germination on solid medium containing isobutyrate or its homologues is discussed.

Biological Factors↗