UNIPROT:P47989 - FACTA Search

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Query: UNIPROT:P47989 (xanthine oxidase)
8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To clarify whether the changes of free radicals and its scavengers are induced by thyroid disorders, we measured levels of free radical scavengers and checked O2 radical generating systems in the human thyroid gland. Thyroid specimens from patients with Graves' disease, follicular adenoma, and papillary and follicular carcinomas contained significantly higher concentrations of xanthine oxidase (XOD) and gluthathione peroxidase (GSH-PX), compared to those in the normal thyroid tissue. Catalase concentration was significantly lower in thyroid specimens from patients with Graves' disease and significantly lower in thyroid specimens from patients with follicular adenoma, compared to those in the normal thyroid tissue. Cu/Zn superoxide dismutase (Cu/Zn SOD) concentration was significantly lower in the specimens from follicular adenoma and papillary carcinoma and Mn SOD concentration was significantly higher in the specimens from papillary carcinoma than those in the normal thyroid tissue. The lipid peroxide concentration, expressed as malondialdehyde (MDA) concentration, was significantly higher in the specimens from papillary carcinoma than those in the normal thyroid tissue. These findings suggest that the levels of free radicals are increased and are scavenged and catalyzed in the thyroid of Graves' disease, whereas free radicals and lipid peroxide are not completely scavenged in papillary carcinoma tissues, suggesting that these substances affect some role in cell function of thyroid tumors.
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PMID:Changes in free radical scavengers and lipid peroxide in thyroid glands of various thyroid disorders. 928 68

Anti-tumor quinone, including mitomycin C (MMC), needs to be activated by bioreduction to exert its cytotoxic activities. The enzymes underlying this bioreductive activation have been the subject of extensive research on Mitomycin C. Cytochrome P450 reductase, cytochrome b5 reductase, xanthine oxidase, xanthine dehydrogenase and DT-diaphorase (DTD) have been shown to be involved in the reduction of MMC. The relationship between bioreductive enzymes and the cytotoxicity of quinone, however, has not been analyzed yet. In this study, we investigated the relationship between the bioreductive enzymes and the cytotoxicity of MMC. We carried out the following experiments and the following results were obtained. I) We isolated an MMC-resistant variant. This cell showed five-fold resistance to MMC as compared with the parental cell line. DTD was deficient in this resistant cell. II) We have examined the bioreductive enzyme activities of DTD and cytochrome P450 reductase and IC50's of MMC in 13 colon and gastric carcinoma cell lines. A positive correlation was not found between the enzyme activities and MMC sensitivities, but the cells with little or no DTD activity showed higher IC50 values compared to the other cell lines. III) To elucidate directly the role of DTD in MMC sensitivity, we introduced NQO1 gene into St-4 cells. NQO1 gene encodes DTD and St-4 cells have no DTD activity. All of the transfectants showed five- to ten-fold higher sensitivity to MMC as compared to the parental St-4 cells. The above data indicate that DTD is a critical determinant of sensitivity to MMC in aerobic conditions.
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PMID:[DT-diaphorase]. 930 61

In our studies to find natural compounds with chemopreventive efficacy in foods, using azoxymethane (AOM)-induced colonic aberrant crypt foci and colonic mucosal cell proliferation as biomarkers, a xanthine oxidase inhibitor, 1'-acetoxychavicol acetate (ACA), present in the edible plant Languas galanga from Thailand was found to be effective. This study was conducted to test the ability of ACA to inhibit AOM-induced colon tumorigenesis when it was fed to rats during the initiation or post-initiation phase. Male F344 rats were given three weekly s.c. injections of AOM (15 mg/kg body weight) to induce colonic neoplasms. They were fed diet containing 100 or 500 ppm ACA for 4 weeks, starting one week before the first dosing of AOM (the initiation feeding). The other groups were fed the ACA diet for 34 weeks, starting one week after the last AOM injection (the post-initiation feeding). At the termination of the study (week 38), AOM had induced 71% incidence of colonic adenocarcinoma (12/17 rats). The initiation feeding with ACA caused significant reduction in the incidence of colon carcinoma (54% inhibition by 100 ppm ACA feeding and 77% inhibition by 500 ppm ACA feeding, P = 0.03 and P = 0.001, respectively). The post-initiation feeding with ACA also suppressed the incidence of colonic carcinoma (45% inhibition by 100 ppm ACA feeding and 93% inhibition by 500 ppm ACA feeding, P = 0.06 and P = 0.00003, respectively). Such inhibition was dose-dependent and was associated with suppression of proliferation biomarkers, such as ornithine decarboxylase activity in the colonic mucosa, and blood and colonic mucosal polyamine contents. ACA also elevated the activities of phase II enzymes, glutathione S-transferase (GST) and quinone reductase (QR), in the liver and colon. These results indicate that ACA could inhibit the development of AOM-induced colon tumorigenesis through its suppression of cell proliferation in the colonic mucosa and its induction of GST and QR. The results confirm our previous finding that ACA feeding effectively suppressed the development of colonic aberrant crypt foci. These findings suggest possible chemopreventive ability of ACA against colon tumorigenesis.
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PMID:Chemoprevention of azoxymethane-induced rat colon carcinogenesis by a xanthine oxidase inhibitor, 1'-acetoxychavicol acetate. 936 29

In this communication, we report that iron overload augments benzoyl peroxide (BPO)-mediated tumor promotion in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated mouse skin. Female albino Swiss mice were overloaded with iron and tumors were initiated by applying a single topical application of DMBA. A week after the initiation, promoting agent, BPO, was applied three times/week for 46 weeks. The appearance of the first tumor (papilloma) and the number of tumors/mouse were recorded. When compared to the control group, the iron-overloaded mice showed an increased incidence of tumors at various time intervals. In iron-overloaded animals, tumors appeared earlier and also the number of tumors/mouse was significantly higher. These data could be correlated with the iron levels of mouse skin in the two groups. Further, BPO-mediated induction in ornithine decarboxylase (ODC) activity and [3H]thymidine incorporation in cutaneous DNA were higher in the iron overload group. In addition, in iron-overloaded mice, cutaneous lipid peroxidation (LPO) and xanthine oxidase (XOD) activities were higher, whereas catalase activity was reduced. Similar to papilloma induction, a significant increase in carcinoma yield and incidence was observed in iron-overloaded animals. Based on this study, we propose that iron overload significantly increases the tumor promotion and progression potential of BPO. We suggest that oxidative stress generated by iron overload is responsible for the augmentation of BPO-mediated cutaneous tumorigenesis.
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PMID:Effect of iron overload on the benzoyl peroxide-mediated tumor promotion in mouse skin. 958 58

In recent years, accumulated evidence indicates that free radical species and nitric oxide (NO) or its derivatives are the key denominators in carcinogenesis. Our present topics discussed in this article will focus on the biological significance of free radical generation induced by viral and bacterial infections. In influenza virus infection in mice, the level of xanthine oxidase (XO) at the infected sites was elevated to a great extent. The timing of paralleled induction of XO with that of inducible NO synthase (iNOS) indicates efficient simultaneous reaction: NO + O2*- --> ONOO- (peroxynitrite). Peroxynitrite formation was identified by immunostaining of nitrotyrosine at the local site of infected organs. Peroxynitrite exhibits unique chemical reactivities such as protein nitration, DNA-strand breakage, guanine nitration, etc., which may then bring about not only cytotoxic effect but also mutagenesis. Numbers of evidence in vitro and in vivo show that treatment with chemical carcinogens such as carbon tetrachloride and heterocyclic amines also generated superoxide. The chronic inflammatory reactions, e.g., zymosan- and silica-induced granuloma, revealed very similar free radical generation in vivo. In addition, most experimental solid tumors have elevated levels of iNOS in the tumor tissue, and NO thus generated facilitates vascular permeability, which accelerates nutritional supply to the tumor tissue and hence sustains the rapid tumor growth. These circumstantial evidences suggest that inflammatory responses induced by various pathogens would accelerate mutagenesis as well as tissue damage, whereas NO also sustains more effectively solid tumor growth when normal cells are transformed to tumor or carcinoma cells by the host-derived free radical species.
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PMID:Nitric oxide and oxygen radicals in infection, inflammation, and cancer. 972 38

The impact of nitric oxide (NO) synthesis on different biological cascades can rapidly change dependent on the rate of NO formation and composition of the surrounding milieu. With this perspective, we used diaminonaphthalene (DAN) and diaminofluorescein (DAF) to examine the nitrosative chemistry derived from NO and superoxide (O2-) simultaneously generated at nanomolar to low micromolar per minute rates by spermine/NO decomposition and xanthine oxidase-catalyzed oxidation of hypoxanthine, respectively. Fluorescent triazole product formation from DAN and DAF increased as the ratio of O2- to NO approached equimolar, then decreased precipitously as O2- exceeded NO. This pattern was also evident in DAF-loaded MCF-7 carcinoma cells and when stimulated macrophages were used as the NO source. Cyclic voltammetry analysis and inhibition studies by using the N2O3 scavenger azide indicated that DAN- and DAF-triazole could be derived from both oxidative nitrosylation (e.g., DAF radical + NO) and nitrosation (NO+ addition). The latter mechanism predominated with higher rates of NO formation relative to O2-. The effects of oxymyoglobin, superoxide dismutase, and carbon dioxide were examined as potential modulators of reactant availability for the O2- + NO pathway in vivo. The findings suggest that the outcome of NO biosynthesis in a scavenger milieu can be focused by O2- toward formation of NO adducts on nucleophilic residues (e.g., amines, thiols, hydroxyl) through convergent mechanisms involving the intermediacy of nitrogen dioxide. These modifications may be favored in microenvironments where the rate of O2- production is temporally and spatially contemporaneous with nitric oxide synthase activity, but not in excess of NO generation.
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PMID:Focusing of nitric oxide mediated nitrosation and oxidative nitrosylation as a consequence of reaction with superoxide. 1217 14

Treatment of carcinoma cell lines with 15-deoxy-delta12,14-prostaglandin J2 (15d-PGJ2), a natural ligand of the peroxisome proliferator-activated receptor-gamma, has been reported to induce apoptosis and/or inhibit proliferation. In this study, we investigated the cytotoxic effect and the action mechanisms of 15d-PGJ2 in a thyroid papillary cancer cell line, CG3. The results indicate that 15d-PGJ2 caused cytotoxicity and increased the amount of intracellular reactive oxygen species (ROS) in these cells. Mitochondrial oxidative phosphorylation inhibitors (carbonyl cyanide m-chloro-phenylhydrazone, oligomycin, cyclosporin A and rotenone), NADPH oxidase inhibitor (diphenyleneiodonium), xanthine oxidase inhibitor (allopurinol) and NO synthase inhibitor (N-monomethyl-L-arginine acetate) did not reduce the generation of ROS. However, catalase, N-acetyl-cysteine and the iron chelator desferri-oxamine decreased the intracellular ROS of 15d-PGJ2-treated CG3 cells. Furthermore, 15d-PGJ2 enhanced the accumulation of iron in the CG3 cells. These data suggest that 15d-PGJ2 induces the generation of ROS by enhancing the accumulation of intracellular iron and that the increased oxidative stress may cause apoptosis of CG3 cells.
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PMID:15-Deoxy-delta12,14-prostaglandin J2 induces apoptosis of a thyroid papillary cancer cell line (CG3 cells) through increasing intracellular iron and oxidative stress. 1218 33

Geum quellyon Sweet, a perennial herb of the Rosaceae family, has been used in the traditional medicine of the Mapuche Amerindians of Chile to treat tooth neuralgia, gastric inflammation, prostatitis and to regulate menstruation, and for its diuretic and aphrodisiac properties. Although many benefits have been claimed for this plant, few scientific studies are available in the literature. In this study, we investigated the antioxidant activity of a methanolic extract of Geum quellyon roots. We also examined the anticancer action of this plant on Caco-2 (colon adenocarcinoma cells), DU-145 (androgen-insensitive prostate cancer cells) and KB (oral squamous carcinoma cells) human tumor cell lines. Our data showed that Geum quellyon extract, containing tannins, exhibits interesting antioxidant properties, expressed by its capacity to scavenge 1,1-diphenyl-2-picryl-hydrazyl radical (DPPH) and superoxide anion (O(2)*-), to inhibit xanthine oxidase activity, to chelate metals, and to protect plasmid DNA from cleavage induced by hydroxyl radicals (*OH) and nitric oxide (NO). These results may explain, at least in part, its use in Mapuche traditional medicine for gastric inflammation and prostatitis. The assays on human tumor cell lines demonstrated that this natural product exhibits a inhibitory effect on all human cancer cells examined, and seem to indicate that necrosis cell death is triggered in KB cells and Caco-2, while apoptotic cell demise appears to be induced in DU-145. The effect evidenced in Caco-2 cells can be in part correlated to a modulation of redox-sensitive mechanisms.
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PMID:Antioxidant activity and antiproliferative action of methanolic extract of Geum quellyon Sweet roots in human tumor cell lines. 1594 35

To target malignant cells residing in hypoxic regions of solid tumors, we have designed and synthesized prodrugs generating the cytotoxic alkylating species 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)hydrazine (90CE) after bioreductive activation. We postulate that one of these agents, 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2-[[1-(4-nitrophenyl)ethoxy]carbonyl]hydrazine (KS119), requires enzymatic nitro reduction to produce 90CE, whereas another agent, 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(4-nitrobenzyloxy)carbonyl]hydrazine (PNBC), can also be activated by nucleophilic attack by thiols such as glutathione (GSH)/GST. We demonstrated that these agents selectively kill hypoxic EMT6 mouse mammary carcinoma and CHO cells. In hypoxia, 50 microM KS119 produced 5 logs of kill of EMT6 cells without discernable cytotoxicity in air; similar effects were observed with CHO cells. PNBC was less efficacious against hypoxic tumor cells and also had some toxicity to aerobic cells, presumably because of GST/thiol activation, making PNBC less interesting as a selective hypoxic-cell cytotoxin. BALB/c mice with established EMT6 solid tumors were used to demonstrate that KS119 could reach and kill hypoxic cells in solid tumors. To gain information on bioreductive enzymes involved in the activation of KS119, cytotoxicity was measured in CHO cell lines overexpressing NADH:cytochrome b5 reductase (NBR), NADPH:cytochrome P450 reductase (NPR), or NADPH: quinone oxidoreductase 1 (NQO1). Increased cytotoxicity occurred in cells overexpressing NBR and NPR, whereas overexpressed NQO1 had no effect. These findings were supported by enzymatic studies using purified NPR and xanthine oxidase to activate KS119. KS119 has significant potential as a hypoxia-selective tumor-cell cytotoxin and is unlikely to cause major toxicity to well oxygenated normal tissues.
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PMID:1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-[[1-(4-nitrophenyl)ethoxy]carbonyl]hydrazine: an anticancer agent targeting hypoxic cells. 1596 88

Carotenoid fractions were extracted from red paprika, Valencia orange peel and the peel of Golden delicious apple. Thus, hypophasic carotenoids of paprika (PM1), orange (PM3) and apple (PM4), and epiphasic extractions of paprika (PM2) and apple (PM5) were obtained by extraction, saponification and partition between MeOH-H(2)O (9:1) (hypophasic) and hexane (epiphasic). A high content of capsanthin was quantified in hypophasic carotenoids (PM1) from red spice paprika, whereas the hypophasic fractions from orange (PM3) and apple (PM4) were mainly composed of violaxanthin, zeaxanthin and lutein. On the other hand, a high content of beta,beta-carotene and beta-cryptoxanthin was found in epiphasic fractions (PM2 and PM5). The extracts were studied for their anti-Helicobacter pylori (H. pylori), anti-human immunodeficiency virus (HIV), cytotoxic, multidrug resistance (MDR) reversal and radical scavenging activity. Among five PM extracts and beta,betacarotene, PM4 showed potent anti-H. pylori activity (MIC(50) = 36 microg/mL), comparable to metronidazole (MIC(50) = 45 microg/mL). The extracts were inactive against HIV. PM3 and PM4 showed slightly higher cytotoxic activity against three human tumor cell lines (squamous cell carcinoma HSC-2, HSC-3, submandibular gland carcinoma HSG) and human promyelocytic leukemic HL-60 cells than against three normal human oral cells (gingival fibroblast HGF, pulp cell HPC, periodontal ligament fibroblast HPLF), suggesting a tumor-specific cytotoxic activity. PM1, PM3 and PM4 displayed much higher MDR-reversing activity than (+/-)-verapamil. ESR spectroscopy demonstrated that PM1-5 and beta,beta-carotene produced little or no detectable radical under alkaline conditions and did not scavenge the O(2) (-) produced by the hypoxanthine and xanthine oxidase reaction. On the other hand, PM1 and PM2 scavenged efficiently 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, whereas singlet oxygen was also quenched efficiently by PM5 and PM2. The data suggest the potential importance of carotenoids as possible anti-H. pylori and MDR reversal agents. The active principles in the carotenoid extract might differ, depending upon the types of fruits and vegetables.
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PMID:Biological activity of carotenoids in red paprika, Valencia orange and Golden delicious apple. 1617 74

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