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)

Both cooked red meat intake and chronic inflammation/infection are thought to play a role in the etiology of colon cancer. The heterocyclic amine 2-amino-3-methylimidazo[4,5-f ]quinoline (IQ) is formed during cooking of red meat and may be involved in initiation of colon cancer. Reactive nitrogen oxygen species (RNOS), components of the inflammatory response, contribute to the deleterious effects attributed to inflammation on normal tissues. This study assessed the possible chemical transformation of IQ by RNOS. RNOS were generated by various conditions to react with (14)C-IQ, and samples were evaluated by HPLC. Myeloperoxidase (MPO)-catalyzed reaction was dependent upon both H(2)O(2) and NO(2)(-). This reaction produced an azo-IQ dimer and IQ dimer along with two nitrated IQ products identified by ESI/MS. 2-Nitro-IQ was not detected. Product formation was inhibited by 2 mM cyanide. Reduction in nitrated products observed with 100 mM chloride was not altered with 0.5 mM taurine. Nitrated products were also produced by other conditions, ONOO(-) and NO(2)(-) + HOCl, which generate nitrogen dioxide radical. In contrast, conditions which generate N(2)O(3), such as diethylamine NONOate, produced only small amounts of nitrated products with the major product identified by MS and NMR as N-nitroso-IQ. MPO activation of IQ to bind DNA was dependent upon both H(2)O(2) and NO(2)(-). RNOS generated by ONOO(-) and DEA NONOate also activated IQ DNA binding. The nitrated IQ products were not activated by MPO to bind DNA. In contrast, N-nitroso-IQ was activated to bind DNA by MPO +/- NO(2)(-). HOCl activated N-nitroso-IQ, but not IQ. RAW cells produced N-nitroso-IQ and increased amounts of NO(2)(-)/NO(3)(-), when incubated with 0.1 mM IQ and stimulated with lipopolysaccharide and interferon gamma. Results demonstrate chemical transformation and activation of IQ by RNOS and activation of its N-nitroso product by biological oxidants, events which may contribute to initiation of colon cancer.
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PMID:Nitrosation and nitration of 2-amino-3-methylimidazo[4,5-f]quinoline by reactive nitrogen oxygen species. 1218 90

Titanocene dichloride exhibits anti-proliferative activity in a wide spectrum of murine and human tumors. Although it is still unclear as to which species are active in biological media, they all readily deliver Ti(IV) to transferrin, the protein that transports iron in the blood. In this article, we report that aging of the complex in alcohols (namely methanol and ethanol) or dimethyl sulfoxide, the co-solvents used to prepare mother solution of the drug, leads to increased cytotoxic activity (i.e. lower IC(50) values) in HCT116 colon cancer cell lines, to a different extent. The TiCp(2)Cl(2) solvolysis was followed by (1)H NMR, ESI-MS, electrochemical and conductivity measurements, and the intracellular Ti(IV) uptake was evaluated.
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PMID:Enhancement of the cytotoxicity of titanocene dichloride by aging in organic co-solvent. 1620 87

In addition to 7-methoxy-2-methyl-3,4,5-trihydroxyanthraquinone (1), physcion (2), macrosporin (3), deoxybostrycin (4), altersolanol B (5) and dactylariol (6), a new hexahydroanthraquinone named pleospdione (7) was isolated from the culture of Pleospora sp . IFB-E006, an endophytic fungus residing in the normal stem of Imperata cylindrical (Gramineae). Structure determination of pleospdione was accomplished using IR, HR-ESI-MS, 1D and 2D NMR spectral analysis. Compounds 4 - 6 exhibited significant cytotoxic activity against human colon cancer (SW1116) and leukemia (K562) cell lines while compounds 1, 2 and 7 were only weakly or moderately active.
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PMID:New and cytotoxic anthraquinones from Pleospora sp. IFB-E006, an endophytic fungus in Imperata cylindrical. 1632 Feb 10

To gain a better understanding of the mechanism underlying colon cancer and to search for potential markers of colon cancer prognosis, a comparative proteomic analysis of colon cancer WiDr cells was conducted using 2-DE and lectin blot, followed by identification based on ESI-MS. Through these approaches 14 proteins were identified as candidate target proteins for N-acetylglucosaminyl transferase V (GnT-V) that would be expected to be implicated in the progression of colon cancer. We selected protein tyrosine phosphatase kappa (PTPkappa) as a model protein to validate this approach to the discovery of novel biomarkers in colon cancer. PTPkappa underwent an aberrant glycosylation in GnT-V-overexpressing WiDr cells, and the aberrantly glycosylated PTPkappa was vulnerable to proteolytic cleavage. The enhanced cleavage of PTPkappa in GnT-V-overexpressing cells was responsible for the mitigation of the homophilic binding capacity, resulting in an increase in cancer cell migration.
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PMID:Identification of target proteins of N-acetylglucosaminyl transferase V in human colon cancer and implications of protein tyrosine phosphatase kappa in enhanced cancer cell migration. 1640 19

Tetraspanins are integral membrane proteins involved in a variety of physiological and pathological processes. In cancer, clinical and experimental studies have reported a link between tetraspanin expression levels and metastasis. Tetraspanins play a role as organizers of a molecular network of interactions, the "tetraspanin web". Here, we have performed a proteomic characterization of the tetraspanin web using a model of human colon cancer consisting of two cell lines derived from primary tumor and metastasis from the same patient. The tetraspanin complexes were isolated after immunoaffinity purification and the proteins were identified by MS using LC-ESI-MS/MS and MALDI-FTICR. The high resolution and mass accuracy of FTICR MS allowed reliable identification using mass finger printing with only two peptides. Thus, it could be used to resolve the composition of complex peptide mixtures from membrane proteins. Different types of membrane proteins were identified, including adhesion molecules (integrins, Lu/B-CAM, GA733 proteins), receptors and signaling molecules (BAI2, PKC, G proteins), proteases (ADAM10, TADG15), and membrane fusion proteins (syntaxins) as well as poorly characterized proteins (CDCP1, HEM-1, CTL1, and CTL2). Some components were differentially detected in the tetraspanin web of the two cell lines. These differences may be relevant for tumor progression and metastasis.
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PMID:Proteomic analysis of the tetraspanin web using LC-ESI-MS/MS and MALDI-FTICR-MS. 1640 22

The application of reversed-phase high-pressure liquid chromatography under gradient conditions and electrospray ion trap mass spectrometry (LC-ESI-MS) to the analysis of global modification levels of core histones is described. The optimised LC-ESI-MS method was applied for the first time to the characterisation of histones extracted from HT29, a human colon cancer cell line. Eight histones (H1-1, H1-2, H2A-1, H2A-2, H2B, H3-1, H3-2, H4) were separated on a C4 stationary phase with complete resolution, never reached in previous HPLC-MS methods, by using a gradient elution with the combined presence of heptafluorobutyric acid and formic acid as acidic modifiers in the mobile phase. Heptafluorobutyric acid was found to improve selectivity, whereas the presence of formic acid decreased ion suppression. Histones eluted from the column were detected with an ion trap mass spectrometer with an electrospray source. The peak averaged mass spectra were reconstructed by Mag Tran 1.0 software and the mass of the various isoforms of histones were derived. Method validation was conducted by performing the same sample analysis by coupling LC-ESI to a quadrupole-time-of-flight mass spectrometer (Q-TOF). The number of histone forms and their mass were found to differ not significantly from those obtained by ion trap mass spectrometer. Also the relative modifications abundance within the same histone type was found following the same trend as the two mass analysers. This method was then applied to the characterisation of changes in histone modification in HT29, never analysed by LC-MS before, treated with histone deacetylase inhibitors such as valproate and sodium butyrate, also used in preclinical trials as anticancer drugs. In particular, both the inhibitors produced a significant increase in H4 histone acetylated forms: 89% increase of the diacetyl dimethyl H4 form was observed with 1mM valproate supplementation, whereas 5 mM butyrate led to a 68% increase of the same form. Triacetyl monomethyl H4 (11,377 Da) and triacetyl dimethyl H4 (11,390 Da) were found only in cells treated with butyrate. Selective changes of H3 histone were detected with butyrate, in agreement with recently reported western blotting studies. Modifications in the H2A histone degree of acetylation were revealed by treatment of the cells with butyrate (H2A-1, H2A-2) and valproate (H2A-2). The results of the proposed methodology confirmed that inhibition of histone deacetylases caused histone hyperacetylation, responsible for decondensation and reorganization of interphase dynamic chromatin. This method resulted in selective and sensitive method to monitor variations in the acetylation and methylation state of histones after treatment of HT29 with inhibitors, and is therefore suitable for further application in new drug discovery for tumour therapy.
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PMID:Histone proteins determined in a human colon cancer by high-performance liquid chromatography and mass spectrometry. 1688 28

Berry fruits are widely consumed in our diet and have attracted much attention due to their potential human health benefits. Berries contain a diverse range of phytochemicals with biological properties such as antioxidant, anticancer, anti-neurodegerative, and anti-inflammatory activities. In the current study, extracts of six popularly consumed berries--blackberry, black raspberry, blueberry, cranberry, red raspberry and strawberry--were evaluated for their phenolic constituents using high performance liquid chromatography with ultraviolet (HPLC-UV) and electrospray ionization mass spectrometry (LC-ESI-MS) detection. The major classes of berry phenolics were anthocyanins, flavonols, flavanols, ellagitannins, gallotannins, proanthocyanidins, and phenolic acids. The berry extracts were evaluated for their ability to inhibit the growth of human oral (KB, CAL-27), breast (MCF-7), colon (HT-29, HCT116), and prostate (LNCaP) tumor cell lines at concentrations ranging from 25 to 200 micro g/mL. With increasing concentration of berry extract, increasing inhibition of cell proliferation in all of the cell lines were observed, with different degrees of potency between cell lines. The berry extracts were also evaluated for their ability to stimulate apoptosis of the COX-2 expressing colon cancer cell line, HT-29. Black raspberry and strawberry extracts showed the most significant pro-apoptotic effects against this cell line. The data provided by the current study and from other laboratories warrants further investigation into the chemopreventive and chemotherapeutic effects of berries using in vivo models.
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PMID:Blackberry, black raspberry, blueberry, cranberry, red raspberry, and strawberry extracts inhibit growth and stimulate apoptosis of human cancer cells in vitro. 1714 15

Glucose deprivation, a feature of poorly vascularized solid tumors, activates the unfolded protein response (UPR) which is a stress-signaling pathway in tumor cells that is associated with the molecular chaperone GRP78 and induction of GRP78 has been shown to protect them against programmed cell death. Thus, targeting glucose-deprived conditions may be a novel strategy in anticancer drug development. Based on that, we established a novel screening program for chaperone modulators that preferentially cytotoxic activity in cancer cells under glucose-deprived conditions. During the course of our screening system, we recently isolated an active compound, 326-2, from Penicillium verrucosum var. cyclopium and identified it as a down-regulator of the grp78 gene. As expected, 326-2 inhibited the expression of the GRP78 promoter under glucose-deprived conditions in a dose-dependent manner with an IC(50) value of 50nM. Furthermore, 326-2 was identified as verrucosidin, a pyrone-type polyketide, by ESI-MS analyses and various NMR spectroscopic methods. We found that verrucosidin prevents UPR-induced expression of protein, such as GRP78, whose expression is induced by glucose-deprived or by 2-deoxyglucose; this effect is not seen under normal growth conditions. The GRP78-inhibitory action of verrucosidin was dependent on strict hypoglycemic conditions and resulted in selective cell death of glucose-deprived HT-29 human colon cancer cells.
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PMID:Glucose-deprived HT-29 human colon carcinoma cells are sensitive to verrucosidin as a GRP78 down-regulator. 1716 15

Anthocyanins are polyphenol antioxidants that have been shown to prevent many chronic diseases, including colon cancer. The compounds are largely metabolized by various enzymes and bacteria in the large intestine, and the health benefits of consuming foods rich in anthocyanins could be due mostly to the effects of these metabolites. In this study, the contents of the large intestine of pigs were used to model anthocyanin metabolism because pig and human intestinal microflora are similar. An anthocyanin extract from Cabernet Sauvignon grapes that contained delphinidin-3-glucoside, petunidin-3-glucoside, peonidin-3-glucoside, and malvidin-3-glucoside was employed. The extract was incubated anaerobically in the contents of the large intestine of freshly slaughtered pigs for 0, 0.5, and 6 h (final concentrations of 20.9, 28.2, 61.4, and 298.0 microM of the above anthocyanin compounds, respectively, at t = 0 h). Anthocyanins and their metabolites were measured by LC-ESI-MS. After 6 h, anthocyanins were no longer detected, and three metabolites were identified as 3-O-methylgallic acid, syringic acid, and 2,4,6-trihydroxybenzaldehyde. Results from this study suggest that consumption of Cabernet Sauvignon grape anthocyanins could lead to the formation of specific metabolites in the human gut, and it is possible that these metabolites offer the protective effect against colon cancer attributed to anthocyanin consumption.
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PMID:Identification of Cabernet Sauvignon anthocyanin gut microflora metabolites. 1876 60

A new p-hydroxyphenylacetyl flavonoid, diosmetin 7-(6''-O-p-hydroxyphenylacetyl)-O-beta-d-glucopyranoside (1), was isolated from the flowers of Chrysanthemum morifolium Ramat. 'huaiju' cv. nov. (Compositae), together with five known flavonoids, luteolin (2), diosmetin (3), diosmetin 7-O-beta-d-glucopyranoside (4), diosmin (5), and scolimoside (6), and four known caffeoylquinic acid derivatives, macranthoin F (7), 3,5-dicaffeoylquinic acid (8), 1,3-dicaffeoyl-epi-quinic acid (9), and chlorogenic acid (10). The structure of 1 was elucidated by UV, IR, ESI-TOF-MS, 1D, and 2D NMR spectroscopic methods. Cytotoxic activity of compounds 1-5 against human colon cancer cell Colon205 was investigated using MTT assays. Compounds 2 and 3 showed significant cytotoxicities against Colon205, with their IC(50) values being 96.9 and 82.9 microM, respectively. However, compounds 1, 4, and 5 showed little cytotoxic activity.
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PMID:Cytotoxic activity of flavonoids from the flowers of Chrysanthemum morifolium on human colon cancer Colon205 cells. 2018 23


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