Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hexane extract from the bark of Amphipterygium adstringens, as well as its principal constituents, masticadienonic acid and 3alpha-hydroxymasticadienolic acid, inhibited the growth of five human cancer cell lines. Derivatives of, namely 24,25 S-dihydromasticadienonic acid and masticadienolic acid, were also evaluated. The results showed that both and had greater activity than on colon cancer cell lines. The effects of on the production of nitric oxide (NO) from both resting and lipopolysaccharide-activated macrophages were determined. It was found that and caused an increase in NO release from resting macrophages; in lipopolysaccharide-activated macrophages, only and caused an increase in NO production.
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PMID:Cytotoxic activity and effect on nitric oxide production of tirucallane-type triterpenes. 1610 29

Intestinal epithelial cells not only present a physical barrier to bacteria but also participate actively in immune and inflammatory responses. The migration of epithelial cells from the crypt base to the surface is accompanied by a cellular differentiation that leads to important morphological and functional changes. It has been reported that the differentiation of colonic epithelial cells is associated with reduced interleukin (IL)-8 responses to IL-1beta. Although toll-like receptor 4 (TLR4) has been previously identified to be an important component of mucosal immunity to lipopolysaccharide (LPS) in the colon, little is known about the regulation of TLR4 in colonic epithelial cells during cellular differentiation. We investigated the effects of differentiation on LPS-induced IL-8 secretion and on the expression of TLR4. Differentiation was induced in colon cancer cell line HT-29 cells by butyrate treatment or by post-confluence culture and assessed by measuring alkaline phosphatase (AP) activity. IL-8 secretion was measured by ELISA, and TLR4 protein and mRNA expressions were followed by Western blot and RT-PCR, respectively. HT-29 cells were found to be dose-dependently responsive to LPS. AP activity increased in HT-29 cells by differentiation induced by treatment with butyrate or post-confluence culture. We found that IL-8 secretion induced by LPS was strongly attenuated in differentiated cells versus undifferentiated cells, and that cellular differentiation also attenuated TLR4 mRNA and protein expressions. Pretreating HT-29 cells with tumor necrosis factor (TNF)-alpha or interferon (INF)-gamma augmented LPS-induced IL-8 secretion and TLR4 expression. These TNF-alpha- or INF-gamma-induced augmentations of LPS response and TLR4 expression were all down-regulated by differentiation. Collectively, we conclude that cellular differentiation attenuates IL-8 secretion induced by LPS in HT-29 cells, and this attenuation is related with the down-regulation of TLR4 expression.
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PMID:Cellular differentiation-induced attenuation of LPS response in HT-29 cells is related to the down-regulation of TLR4 expression. 1620 85

Inhibitory effect of kudzu isoflavones on arachidonic acid metabolism and nitric oxide (NO) production in lipopolysaccharide activated RAW 264.7 macrophages were investigated. Isoflavone aglycones, such as daidzein, genistein, biochanin A, and formononetin significantly suppressed arachidonic acid release (50 microM). Biochanin A, which displayed the most active inhibition on arachidonic acid release in HT-29 human colon cancer cells, exhibited its most potent suppression in RAW 264.7 cell (by 86%) without showing cytotoxicity. However, isoflavone glucosides, puerarin and daidzin, showed lower inhibitory activities on the release of arachidonic acid and its metabolites. In NO formation, biochanin A showed marked inhibition, by 62% (50 microM), followed by genistein, daidzein, formononetin, and daidzin, 56, 39, 33, and 8%, respectively. 5,7-Dihydroxyl group in the A-ring of isoflavones could be a key functional group responsible for the strong inhibitory activity of biochanin A and genistein on NO production. These activities may contribute to the antiinflammatory and anticarcinogenic properties of kudzu isoflavones.
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PMID:Suppression of arachidonic acid metabolism and nitric oxide formation by kudzu isoflavones in murine macrophages. 1625 87

Dendritic cell (DC) vaccine is a promising immunotherapy for malignancies, but its clinical efficacy has been questioned. Here we examined the mechanisms of treatment failure with DC vaccine in a murine colon cancer model. DC vaccination of naive mice prevents tumor implantation, but it is ineffective in tumor-bearing hosts despite the induction of tumor-specific CTL activity. Analyses of tumor-specific T helper cell type 1 (Th1)/T helper cell type 2 (Th2) responses showed that DC vaccine induced a mixed Th1/Th2 response in naive mice. Interestingly, CD4+ T cells from tumor-bearing mice showed a Th1-predominant response before DC vaccination but Th2 after DC vaccination. Furthermore, interleukin-10 production was higher in CD4+ T cells from vaccinated tumor-bearing mice than in CD4+ T cells from unvaccinated tumor-bearing mice. CD4+ T cells from mice treated with lipopolysaccharide (LPS)-matured DC fusion vaccine had lower production of interleukin-10 than CD4+ T cells from mice treated with non-LPS-treated DC vaccine. However, similar to the non-LPS-treated DC vaccine, the LPS-matured DC vaccine failed to suppress tumor growth and induced a Th2 predominant tumor-specific response in tumor-bearing mice. These results suggest that the presence of tumor in the host induces an aberrant CD4+ T cell response to DC vaccine, which may contribute to the failure of the vaccine to eradicate established tumors.
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PMID:Aberrant T helper cell response in tumor-bearing mice limits the efficacy of dendritic cell vaccine. 1638 58

(-)-Epigallocatechin-3-gallate (EGCG) is the widely studied catechin in green tea (Camellia sinensis). Previously, we have reported the low bioavailability of EGCG in rats and mice. As a means of improving the bioavailability of EGCG, we have prepared a peracetylated EGCG derivative (AcEGCG) and herein report its growth inhibitory activity and cellular uptake in vitro, as well as bioavailability in mice. AcEGCG exhibited enhanced growth inhibitory activity relative to EGCG in both KYSE150 human esophageal (IC50 = 10 versus 20 microM) and HCT116 human colon cancer cells (IC50 = 32 versus 45 microM). AcEGCG was rapidly converted to EGCG by HCT116 cells, and treatment of cells with AcEGCG resulted in a 2.8- to 30-fold greater intracellular concentration of EGCG as compared with treatment with EGCG. AcEGCG was also more potent than EGCG at inhibiting nitric oxide production (4.4-fold) and arachidonic acid release (2.0-fold) from lipopolysaccharide-stimulated RAW264.7 murine macrophages. Intragastric administration of AcEGCG to CF-1 mice resulted in higher bioavailability compared with administration of equimolar doses of EGCG. The plasma area under the curve from 0 to infinity (AUC0-->infinity) of total EGCG was 465.0 and 194.6 [(microg/ml) . min] from the administration of AcEGCG and EGCG, respectively. The t1/2 of EGCG was also increased following administration of AcEGCG compared with EGCG (441.0 versus 200.3 min). The AUC0-->infinity and t1/2 were also increased in small intestinal (2.8- and 4.3-fold, respectively) and colonic tissues (2.4- and 6.0-fold, respectively). These data suggest that acetylation represents a means of increasing the biological potency in vitro, increasing the bioavailability of EGCG in vivo, and may improve cancer-preventive activity.
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PMID:Peracetylation as a means of enhancing in vitro bioactivity and bioavailability of epigallocatechin-3-gallate. 1699 10

Adjuvants are essential components of vaccines that augment an immunological reaction of organism. New vaccines based on recombinant proteins and DNA, are more save than traditional vaccines but they are less immunogenic. Therefore, there is an urgent need for the development of new, improved vaccine adjuvants. There are two classes of adjuvants: vaccine delivery systems (e.g. emulsions, microparticles, immune-stimulating complexes ISCOMs, liposomes) and immunostimulatory adjuvants (e.g. lipopolysaccharide, monophosphoryl lipid A, CpG DNA, or muramylpeptides). The discovery of more potent and safer adjuvants may allow to development better prophylactic and therapeutic vaccines against chronic infectious (e.g., HSV, HIV, HCV, HBV, HPV, or Helicobacter pylori) and noninfectious diseases as multiple sclerosis, insulin-dependent diabetes, rheumatoid arthritis, allergy and tumors (e.g., melanoma, breast, or colon cancer).
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PMID:[Adjuvants--essential components of new generation vaccines]. 1707 10

Nitric oxide (NO) is a highly reactive free radical that modulates tumorigenesis through its ability to regulate cell proliferation, cell death, migration and angiogenesis. Although the role of NO has been well studied in inflammatory cells, much less is known about the regulation of NO production in epithelial cells. We demonstrated that in intestinal epithelial cells the expression of inducible NO synthase (iNOS), the critical enzyme in the synthesis of NO, is synergistically stimulated by bacterial lipopolysaccharide (LPS) and interferon gamma (IFNgamma) or by the combination of tumor necrosis factor (TNF) and IFNgamma at the transcriptional level. Expression of iNOS and the production of NO in response to LPS/IFNgamma were significantly increased upon induction of oncogenic K-Ras, underlying frequently elevated expression of iNOS in colon cancer. Silencing of STAT1, a major transcription factor involved in signaling by IFNgamma, or pharmacological inhibition of JAKs, kinases that phosphorylate STATs, prevented the induction of iNOS and the production of NO in response to stimulation of cells with LPS/IFNgamma or TNF/IFNgamma, underscoring the importance of the intact JAK/STAT signaling in the regulation of iNOS expression in intestinal epithelial cells. Butyrate, a histone deacetylase (HDAC) inhibitor and a dietary chemopreventive agent, decreased NO production in macrophages and in intestinal myofibroblasts, consistent with its anti-inflammatory activity. In contrast, in intestinal epithelial cells, butyrate significantly enhanced the expression of iNOS and the production of NO in response to treatment with LPS/IFNgamma. Despite the fact that, like butyrate, three structurally unrelated inhibitors of HDAC activity, trichostatin A, suberoylanilide hydroxamic acid, and apicidin, induced acetylation of H3 and H4 in epithelial cells, they failed to increase the production of NO, demonstrating that butyrate regulates NO production in epithelial cells in an HDAC-independent manner. The ability of butyrate to regulate the production of NO in a variety of cell types is likely to underlie its potent chemopreventive and anti-inflammatory activity.
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PMID:Essential role of the JAK/STAT1 signaling pathway in the expression of inducible nitric-oxide synthase in intestinal epithelial cells and its regulation by butyrate. 1725 Nov 86

Toll-like receptors (TLRs) are involved in the production of inflammatory mediators upon specific ligands stimuli. Chemokines are important inflammatory mediators capable of chemoattracting diverse immune cells. In addition to normal immune cells, the expression of TLRs and chemokines has been detected in various tumor cells. However, the roles of TLRs and chemokines expressed by tumor cells in the processes of tumor progression and immune escape have not been fully elucidated. Here we report that TLR4 ligation by lipopolysaccharide (LPS) significantly promotes CT-26 colon cancer cells to produce chemokine CCL20 via activation of TLR4 signaling pathways. We find that LPS treatment of CT-26 cells can significantly increase the chemoattraction of immature dendritic cells (DC) by the autocrine CCL20. Our studies suggest that TLR4 expressed by tumor cells may be involved in the induction of chemokines like CCL20, providing a potential linkage between chronic inflammation and tumor immune escape.
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PMID:TLR4 signaling in cancer cells promotes chemoattraction of immature dendritic cells via autocrine CCL20. 1808 11

In conducting an in vitro screening of ethanol extracts from various natural foods using a human colon cancer cell line (CoLoTC cells), an extract of buckwheat sprouts (ExtBS) was found to express significant anti-inflammatory activity. The anti-inflammatory activity of ExtBS was confirmed by oral administration of lipopolysaccharide (LPS) to mice. Inflammatory cytokines (interleukin 6 and tumor necrosis factor alpha) were markedly up-regulated in the spleen and liver from LPS-administrated mice, and combinatory treatment with LPS and ExtBS decreased up-regulation of them in both cytokines. Both serum cytokine levels corresponded to their gene expressions in tissues, but no anti-inflammatry effect in mice was observed when ExtBS was treated intraperitoneally. ExtBS oral administration also showed protective activity as to hepatic injury induced by galactosamine/LPS treatment. Based on these data, we suggest that ExtBS contains anti-inflammatory compounds.
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PMID:Anti-inflammatory effect of buckwheat sprouts in lipopolysaccharide-activated human colon cancer cells and mice. 1906 Mar 99

Many cancer chemopreventive agents have been associated with lower cancer risk by suppressing nuclear factor-kappaB (NF-kappaB) signaling pathways, which subsequently leads to attenuated pro-inflammatory mediators and activities. Of the natural compounds, the isothiocyanates (ITCs) found in cruciferous vegetables have received particular attention because of their potential anti-cancer effects. However, limited studies regarding the influence of ITCs structure on NF-kappaB transactivation and anti-inflammatory action are reported. In the present study, the anti-inflammatory potential of ten structurally divergent synthetic ITCs were evaluated in HT-29-N9 human colon cancer cells and RAW 264.7 murine macrophages. The effect of ITCs on the basal transcriptional activation of NF-kappaB and the inflammatory response to bacterial lipopolysaccharide (LPS) were assessed. The synthetic ITC analogs suppressed NF-kappaB-mediated pro-inflammatory gene transcription. Among the ITC analogs, tetrahydrofurfuryl isothiocyanate, methyl-3-isothiocyanatopropionate, 3-morpholinopropyl isothiocyanate and 3,4-methyelendioxybenzyl isothiocyanate showed stronger NF-kappaB inhibition as compared to the parent compound, phenylethyl isothiocyanate (PEITC). Molecular analysis revealed that several of the pro-inflammatory mediators and cytokines (iNOS, COX-2, IL-1beta, IL-6 and TNF-alpha) were reduced by ITCs, and correlated with the downregulation of NF-kappaB signaling pathways. Immunoblotting showed that ITCs suppressed LPS-induced phosphorylation and degradation of IkappaB alpha and decreased nuclear translocation of p65. In parallel, ITCs suppressed the phosphorylation of IkappaB kinase alpha/beta (IKKalpha/beta). Taken together, our findings provide the possibility that synthetic ITC analogs might have promising cancer chemopreventive potential, based on their stronger anti-NF-kappaB and anti-inflammatory activities, than the natural ITCs.
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PMID:Anti-NF-kappaB and anti-inflammatory activities of synthetic isothiocyanates: effect of chemical structures and cellular signaling. 1915 19


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