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)

The protective effect of a curcumin analog [bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione] was investigated on hepatic lipid peroxidation (LPO) and antioxidant status during 1,2-dimethylhydrazine-induced colon carcinogenesis in male Wistar rats. The effects were compared with that of curcumin, a known antioxidant and anticarcinogen. Colon cancer was induced by sub-cutaneous injection of DMH at a dosage of 20mg/kg body weight (15 doses, at 1-week intervals). DMH administered rats developed gross tumours in the colon. Enhanced lipid peroxidation in the liver of colon tumour bearing rats was accompanied by a significant decrease in the activities of glutathione peroxidase (GPx), glutathione S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT). Intragastric administration of curcumin (80mg/kg body weight) and curcumin analog (80mg/kg body weight) to DMH-injected rats significantly reduced the number and size of tumour in the colon, lowered lipid peroxidation and enhanced the activities of GPx, GST, SOD and CAT in the liver. We speculate that the curcumin analog used in the present study exerts chemoprevention against cancer development at extrahepatic sites by modulating hepatic biotransformation enzymes and antioxidant status. The effect is comparable with that of curcumin. This shows that the hydroxyl group in the aromatic ring is responsible for the protective effect rather than the methoxy group.
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PMID:Bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione (a curcumin analog) ameliorates DMH-induced hepatic oxidative stress during colon carcinogenesis. 1220 19

Plant-based diets and phytochemicals present in plants are associated with decreased risk of cancer. Brassica species, and broccoli in particular, are associated with reduced risk of several important cancers. Selenium (Se) is an essential nutrient that is covalently bound in a number of different chemical forms found in plants. Broccoli accumulates Se many-fold beyond the concentration of Se in the soil, and the chemical form of Se in broccoli is similar to the chemical form in high-Se garlic, a food with unique chemoprotective properties. Se from broccoli grown to accumulate more than 500 micro g Se/g did not accumulate in rat tissues or increase glutathione peroxidase enzyme activity to the same extent as Se salts or seleno-amino acids. Se from high-Se broccoli decreased the incidence of aberrant crypts in rats with chemically induced colon cancer by more than 50%, compared with controls. Se from high-Se broccoli also decreased the incidence of mammary tumors in rats treated with 7,12-dimethylbenz(a)anthracene (DMBA) and tumor number and volume in APC(min) mice. These results suggest that development of methods to increase the natural accumulation of Se in broccoli may greatly enhance its health-promoting properties.
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PMID:Reduction of cancer risk by consumption of selenium-enriched plants: enrichment of broccoli with selenium increases the anticarcinogenic properties of broccoli. 1280 17

We recently showed that zerumbone, a sesquiterpene found in subtropical ginger, suppresses colonic tumor marker formation in rats and induces apoptosis in colon cancer cell lines. In our present study, the anti-tumor initiating and promoting activities of zerumbone in mouse skin were evaluated using a conventional 2-stage carcinogenesis model. A single topical pretreatment to mouse skin (2 micromol) 24 hr before application of dimethylbenz[a]anthracene (0.2 micromol) markedly suppressed tumor incidence by 60% and the number of tumors by 80% per mouse. Repeated pretreatment (16 nmol) twice weekly during the post-initiation phase reduced the number of 12-O-tetradecanoylphorbol-13-acetate (TPA, 1.6 nmol)-induced tumors by 83% as well as their diameter by 57%. Multiple reverse transcriptase (RT) PCR experiments revealed that zerumbone (2 micromol) enhanced the mRNA expression level of manganese superoxide dismutase, glutathione peroxidase-1, glutathione S-transferase-P1 and NAD(P)H quinone oxidoreductase in the epidermis, but not that of cytochrome p450 1A1 or 1B1. Further, it diminished TPA-induced cyclooxygenase-2 protein expression and phosphorylation of extracellular signal-regulated kinase 1/2, while pretreatment(s), in either the priming or activation stage or both, reduced double TPA application-induced hydrogen peroxide formation and edema induction by 29% to 86%, respectively. Histologic examination revealed that pretreatment(s) with zerumbone suppressed leukocyte infiltration and reduced proliferating cell nuclear antigen-labeling indices. Together, our results indicate that zerumbone is a promising agent for the prevention of both tumor initiating and promoting processes, through induction of anti-oxidative and phase II drug metabolizing enzymes as well as attenuation of proinflammatory signaling pathways.
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PMID:Zerumbone, a sesquiterpene in subtropical ginger, suppresses skin tumor initiation and promotion stages in ICR mice. 1512 79

We showed previously that the dietary combination of fish oil, rich in (n-3) fatty acids, and the fermentable fiber pectin enhances colonocyte apoptosis in a rat model of experimentally induced colon cancer. In this study, we propose that the mechanism by which this dietary combination heightens apoptosis is via modulation of the colonocyte redox environment. Male Sprague-Dawley rats (n = 60) were fed 1 of 2 fats (corn oil or fish oil) and 1 of 2 fibers (cellulose or pectin) for 2 wk before determination of reactive oxygen species (ROS), oxidative DNA damage, antioxidant enzyme activity [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx)] and apoptosis in isolated colonocytes. Fish oil enhanced ROS, whereas the combination of fish oil and pectin suppressed SOD and CAT and enhanced the SOD/CAT ratio compared with a corn oil and cellulose diet. Despite this modulation to a seemingly prooxidant environment, oxidative DNA damage was inversely related to ROS in the fish oil and pectin diet, and apoptosis was enhanced relative to other diets. Furthermore, apoptosis increased exponentially as ROS increased. These results suggest that the enhancement of apoptosis associated with fish oil and pectin feeding may be due to a modulation of the redox environment that promotes ROS-mediated apoptosis.
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PMID:An increase in reactive oxygen species by dietary fish oil coupled with the attenuation of antioxidant defenses by dietary pectin enhances rat colonocyte apoptosis. 1557 18

Oxidative stress is a characteristic of cancerous colon tissue and inflammatory bowel diseases that increase colon cancer risk. Epidemiological evidence supports a protective effect of plant-derived compounds. Aspirin is also protective against colon cancer. The mechanism of action is unclear although salicylic acid, the main metabolite of aspirin, has been shown to decrease the synthesis of pro-inflammatory and potentially neo-plastic prostaglandins. Salicylic acid is found in significant quantities in a plant-based diet. However, in plants salicylic acid is also reported to modulate the expression of numerous enzymes with antioxidant activity. The aim of this study was to assess whether salicylic acid can modulate pro-cancerous biological pathways in the colon. Oxidative stress, prostaglandins and cytosolic glutathione peroxidase (cyGPX) were analysed in proximal, transverse and distal colon from a rat model of diet-induced oxidative stress. Elevated plasma pyruvate kinase activity (1293+/-206 U/ml) and increased indices of lipid peroxidation in colon (proximal 6.4+/-0.84 nM MDA/mg protein; transverse 6.9+/-0.97 nM MDA/mg protein; distal 5.2+/-0.62 nM MDA/mg protein) from rats fed a Vitamin E deficient diet were significantly decreased on supplementation with salicylic acid (plasma pyruvate 546+/-43 U/ml; salicylic acid proximal 3.6+/-0.39 nM MDA/mg protein; transverse 4.5+/-0.61 nM MDA/mg protein; distal 4.4+/-0.27 nM MDA/mg protein). Reductions in oxidative stress and prostaglandin production on supplementation with salicylic acid were associated with an elevation in glutathione peroxidase activity (Vitamin E deficient proximal 0.056+/-0.013 U/mg protein; transverse 0.073+/-0.008 U/mg protein; distal 0.088+/-0.010 U/mg protein; Vitamin E deficient with salicylic acid proximal 0.17+/-0.01 U/mg protein; transverse 0.23+/-0.016 U/mg protein; distal 0.16+/-0.020 U/mg protein). Gpx1 and Gpx2 gene transcripts were not elevated in association with increased activity of the soluble glutathione peroxidase activity. Glutathione peroxidases are key antioxidant enzymes, catalysing the decomposition of potentially toxic lipid peroxides. Gpx activity and regulation of Gpx gene transcription has been shown previously to be complex with activity not necessarily mirrored by a corresponding elevation in gene transcription. By supplementing the diet of Vitamin E deficient rats with salicylic acid (1 g/kg diet), this study assessed effects of salicylic acid on cytosolic glutathione peroxidase activity in the colon. The ability of salicylic acid to modulate antioxidant enzymes in colon tissue may be an important mechanism in inhibiting colon cancer development.
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PMID:Salicylic acid modulates oxidative stress and glutathione peroxidase activity in the rat colon. 1603 82

Colon cancer is the third most common cancer and second leading cause of cancer-related death in the United States. A number of recent articles demonstrate the importance of natural products as cancer chemopreventive agents. In this study, we evaluated the chemopreventive efficacy of luteolin, a flavonoid, on tissue lipid peroxidation and antioxidant status, which are used as biomarkers in DMH-induced experimental colon carcinogenesis. Rats were given a weekly subcutaneous injection of DMH at a dose of 20 mg/kg body weight for 15 weeks. Luteolin (0.2 mg/kg body weight/everyday p.o.) was given to the DMH-treated rats at the initiation and post-initiation stages of carcinogenesis. The animals were killed after 30 weeks. After a total experimental period of 32 weeks (including 2 weeks of acclimatization), tumor incidence was 100% in DMH-treated rats. In those DMH-treated rats that had received luteolin during the initiation or post-initiation stages of colon carcinogenesis, the incidence of cancer and the colon tumor size was significantly reduced as compared to that for DMH-treated rats not receiving luteolin. In the presence of DMH, relative to the results for the control rats, there were decreased levels of lipid peroxidation, as denoted by thiobarbituric acid reactive substances (TBARS), conjugated dienes and lipid hydroperoxides, decreased activities of the enzymic antioxidants superoxide dismutase (SOD) and catalase (CAT), and elevated levels of glutathione and the glutathione-dependent enzymes reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR), and of the non-enzymic antioxidants vitamin C and vitamin E. Our study shows that intragastric administration of luteolin inhibits colon carcinogenesis, not only by modulating lipid peroxidation and antioxidant status, but also by preventing DMH-induced histopathological changes. Our results thus indicate that luteolin could act as a potent chemopreventive agent for colon carcinogenesis.
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PMID:Rat colonic lipid peroxidation and antioxidant status: the effects of dietary luteolin on 1,2-dimethylhydrazine challenge. 1621 61

Glutathione peroxidases (Gpx) are important moderators of oxidative stress that is implicated in the pathogenesis of numerous diseases including colon cancer. Previous studies report limited examinations of cytosolic glutathione peroxidase location of expression in colon tissue. This study reports evidence of both common sites of Gpx1 and Gpx2 expression in rat colon and sites that are exclusive to each isoform. Semi-quantitative PCR performed previously demonstrated RNA expression of Gpx1 and Gpx2 in proximal, transverse and distal colon. Mapping the distribution throughout the entire colon has revealed specific, novel sites of glutathione peroxidase expression in colon lymphatic tissue. In situ hybridisation and immunohistochemistry confirmed micro-anatomical location of Gpx1 within lymphatic tissue and the lamina propria, sub-mucosa, muscularis and serosa, but not the lumenal epithelium. In situ hybridisation and immunohistochemistry were consistent with reports of microanatomical location of Gpx2 in the lumenal epithelium. Novel sites of Gpx2 expression were also observed in lymphatic tissue. Immunolocalisation in the vicinity of aberrant crypt foci was also examined to further investigate the link between glutathione peroxidases and colon cancer. This did not reveal significant abnormalities, nor did measurement of cytosolic glutathione peroxidase activity or gene expression in colon tissue from rats treated with the colontropic chemical, 1,2-dimethylhydrazine. These results support the potential for Gpx1 and Gpx2 redundancy in lymphatic tissue, but not in epithelial cells of the colon crypt or in the lamina propria, sub-mucosa, muscularis or serosa.
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PMID:Novel sites of cytosolic glutathione peroxidase expression in colon. 1622 41

Selenium has been shown to reduce cancer incidence in animal models and more recent data indicate that it may be protective in humans as well. However, little is known about the mechanism by which selenium prevents cancer. Cytosolic glutathione peroxidase (GPX1), a selenium-containing antioxidant enzyme, has been implicated in the development of cancer of the head and neck, lung, and breast, in part because of allelic loss at the GPX1 locus. The study of allelic loss at the GPX1 locus in colon cancer was investigated by examining loss of heterozygosity (LOH) in DNA extracted from both tumor and adjacent histopathologically normal tissue obtained by laser capture microdissection. Tissue samples were obtained from 53 colon cancer patients. Two highly polymorphic markers, alanine codon repeats and a proline-leucine polymorphism (198P/L) present in the GPX1 gene, were used to examine LOH at this locus. Analysis of both polymorphisms identified LOH at GPX1 in a significant percentage of colorectal cancer (42%). These results indicated that LOH at the GPX1 locus is a common event in cancer development and that GPX1 or other tightly linked genes may be involved in the etiology of this disease.
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PMID:Allelic loss of the gene for the GPX1 selenium-containing protein is a common event in cancer. 1631 64

Selenium has cancer protective effects in a variety of experimental systems. Currently, it is not known whether selenoproteins or low molecular weight selenocompounds are responsible for this activity. To evaluate the contribution of selenoproteins to the cancer protective effects of selenium, we used transgenic mice that carry a mutant selenocysteine transfer RNA gene, which causes reduced selenoprotein synthesis. Selenium homeostasis was characterized in liver and colon of wild-type and transgenic mice fed selenium-deficient diets supplemented with 0, 0.1, or 2.0 microg selenium (as selenite)/g diet. (75)Se-labeling, Western blot analysis, and enzymatic activities revealed that transgenic mice have reduced (P < 0.05) liver and colon glutathione peroxidase expression, but conserved thioredoxin reductase expression compared with wild-type mice, regardless of selenium status. Transgenic mice had more (P < 0.05) selenium in the nonprotein fraction of the liver and colon than wild-type mice, indicating a greater amount of low molecular weight selenocompounds. Compared with wild-type mice, transgenic mice had more (P < 0.05) azoxymethane-induced aberrant crypt formation (a preneoplastic lesion for colon cancer). Supplemental selenium decreased (P < 0.05) the number of aberrant crypts and aberrant crypt foci in both wild-type and transgenic mice. These results provide evidence that a lack of selenoprotein activity increases colon cancer susceptibility. Furthermore, low molecular weight selenocompounds reduced preneoplastic lesions independent of the selenoprotein genotype. These results are, to our knowledge, the first to provide evidence that both selenoproteins and low molecular weight selenocompounds are important for the cancer-protective effects of selenium.
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PMID:Both selenoproteins and low molecular weight selenocompounds reduce colon cancer risk in mice with genetically impaired selenoprotein expression. 1661 22

The dietary phenolic compound, salicylic acid, decreases oxidative stress and pro-inflammatory and potentially neo-plastic prostaglandins with a concomitant increase in glutathione peroxidase activity. Salicylic acid, a dietary plant-based phenolic compound and also the main metabolite of aspirin, may contribute to the colon protective effects of plant-based diets. Oxidative stress is a characteristic of pre-cancerous and cancerous colon and inflammatory bowel diseases (IBD) that increase colon cancer risk. The mechanism(s) whereby salicylic acid modulates potentially pro-cancerous activity associated with oxidative stress is further investigated here using a proteomic approach. A rat model of oxidative stress was supplemented with salicylic acid (1 mg/kg diet, mean plasma levels 310+/-32 micromol/l). Soluble colon protein extracts were subjected to 2D PAGE. Salicylic acid modulated proteins, identified using MALDI-TOF and LC/MS/MS, are involved in protein folding, transport, redox, energy metabolism and cytoskeletal regulation. A partial least squares (PLS) analysis approach was used to assist biological interpretation of the altered protein profiles via their associations between previously published biochemical measurements of oxidative stress, prostaglandin levels and increased glutathione peroxidase activity. Early detection of altered homeostasis in colon may assist in identifying pre-pathological features preceding colon tumorigenesis and contribute to an understanding of epidemiological evidence supporting a protective effect of plant-based diets.
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PMID:Salicylate modulates oxidative stress in the rat colon: a proteomic approach. 1673 Jun 65


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