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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The incidence of colon cancer is high in many developed nations, especially New Zealand. Molecular understanding of the nature of colon cancer shows a disease whose well-characterized morphological progression is paralleled at the cellular level by increased numbers of gene or chromosome mutations, loss of heterozygosity, changed methylation patterns, and genomic instability. In the present study, we consider whether an imbalance of factors that affect DNA methylation patterns might explain at least part of the high colon cancer incidence in New Zealand. Folate is the major micronutrient whose intake impacts methylation, particularly through interaction with choline and methionine. Folate is generally somewhat deficient in the New Zealand diet, with the voluntary addition of folate to white flour not producing desired levels. Selenium affects methylation status in several ways and is recognized as being low in New Zealand soils and, therefore, diet. Zinc is also low in the diets of some New Zealand population groups, which can lead to hypomethylation. Several of the components of fruits and vegetables affect methylation patterns, and the average New Zealand intake, at two to three servings per day, is considerably below recommended amounts. Low dietary fiber, high tobacco use, and increasing rates of obesity are also likely New Zealand risk factors that may impact on methylation status. Dietary supplementation is not as common in New Zealand as in countries such as the United States, but may provide a way to raise the levels of nutrients and phytochemicals affecting methylation status, thereby enhancing colon cancer protection.
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PMID:Epigenetic events and protection from colon cancer in New Zealand. 1519 45

The trace element selenium is discussed as a chemopreventive agent in colorectal carcinogenesis. Selenocysteine-containing proteins, so-called selenoproteins, represent potential molecular targets for nutritive selenium supplementation. Due to their antioxidative potential, the selenoproteins gastrointestinal glutathione peroxidase (GI-GPx) and selenoprotein P (SePP) are considered to provide protection against reactive oxygen species (ROS), thereby reducing DNA damage and preventing development of colon cancer. GI-GPx and SePP are abundantly expressed in normal colon mucosa. Recently, we demonstrated both reduced SePP expression and increased GI-GPx expression in colorectal adenomas. In this study, we investigated the expression of SePP and GI-GPx in colorectal cancers compared with corresponding normal mucosa. Further, the occurrence of genetic alterations within the SePP and GI-GPx genes was analyzed. We observed a significant reduction or loss of SePP mRNA expression in colon cancers, whereas GI-GPx mRNA and protein expression varied between different tumor samples. In addition, we identified novel polymorphisms within the SePP and GI-GPx genes with so far unknown relevance for protein function. Our results argue against a general decrease of selenoprotein expression in colorectal carcinogenesis but imply specific differential regulation of expression of individual selenoproteins.
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PMID:Expression profiling and genetic alterations of the selenoproteins GI-GPx and SePP in colorectal carcinogenesis. 1520 72

Epidemiological and preclinical studies suggest that diets that are rich in n-3 polyunsaturated fatty acids (PUFAs) and selenium (Se) reduce the risk of colon cancer. Studies conducted in our laboratory have indicated that synthetic organoselenium 1,4-phenylene bis(methylene) selenocyanate (p-XSC) is less toxic and more effective than inorganic Se and selenomethionine, the major Se compound in natural selenium yeast. Through cDNA microarray analysis, we have demonstrated earlier that the n-3 PUFA docosahexaenoic acid (DHA), modulated more than one signaling pathway by altering several genes involved in colon cancer growth. There is increasing interest in the use of combinations of low doses of chemopreventive agents that differ in their specific modes of action as this approach can minimize toxicity and increase efficacy in model assays. In the present study we assessed the efficacy of DHA and p-XSC individually and in combination at low doses in CaCo-2 colon cancer cells, using cell growth inhibition and apoptosis as measures of chemopreventive efficacy. On the basis of western blot and RT-PCR analysis, we also determined the effects of DHA and p-XSC on the levels of expression of cyclooxygenase-2, inducible nitric oxide synthase, cyclin D1, beta-catenin and nuclear factor kappaB, all of which presumably participate in colon carcinogenesis. A 48 h incubation of CaCo-2 cells with 5 microM each DHA or p-XSC induced cell growth inhibition and apoptosis and altered the expression of the above molecular parameters. Interestingly, the modulation of these cellular and molecular parameters was more pronounced in cells treated with low doses of DHA and p-XSC (2.5 microM each) in combination than in cells treated with these agents individually at higher concentrations (5.0 microM each). These findings are viewed as highly significant since they will provide the basis for the development of combinations of low dose regimens of DHA and p-XSC in preclinical models against colon carcinogenesis and, ultimately, in human clinical trials.
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PMID:Effects of a combination of docosahexaenoic acid and 1,4-phenylene bis(methylene) selenocyanate on cyclooxygenase 2, inducible nitric oxide synthase and beta-catenin pathways in colon cancer cells. 1529 72

Epidemiological studies show that a high intake of anti-oxidant-rich foods is inversely related to cancer risk. While animal and cell cultures confirm the anticancer effects of antioxidants, intervention trials to determine their ability to reduce cancer risk have been inconclusive, although selenium and vitamin E reduced the risk of some forms of cancer, including prostate and colon cancer, and carotenoids have been shown to help reduce breast cancer risk. Cancer treatment by radiation and anticancer drugs reduces inherent antioxidants and induces oxidative stress, which increases with disease progression. Vitamins E and C have been shown to ameliorate adverse side effects associated with free radical damage to normal cells in cancer therapy, such as mucositis and fibrosis, and to reduce the recurrence of breast cancer. While clinical studies on the effect of anti-oxidants in modulating cancer treatment are limited in number and size, experimental studies show that antioxidant vitamins and some phytochemicals selectively induce apoptosis in cancer cells but not in normal cells and prevent angiogenesis and metastatic spread, suggesting a potential role for antioxidants as adjuvants in cancer therapy.
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PMID:Dietary antioxidants and human cancer. 1552 4

Multiple components of broccoli, such as sulforaphane (Sf) and phenolic acids, may inhibit cancer. Additionally, broccoli can accumulate selenium (Se), and Se has been demonstrated to reduce the risk of cancer. Studies were conducted to determine whether enhancement of broccoli with Se would produce a plant with superior health benefits. Although increasing the concentration of Se in broccoli from <1.0 to >800 microg/g resulted in inhibition of colon cancer in rats, it also decreased the Sf content by >80% and inhibited production of most phenolic acids. The inclusion of Se-enriched broccoli in the diet of rats induced the activity of the selenoprotein thioredoxin reductase beyond the maximum activity induced by Se alone. These results emphasize the complex interactions of bioactive chemicals in a food; attempts to maximize one component may affect accumulation of another, and consumption of high amounts of multiple bioactive compounds may result in unexpected metabolic interactions within the body.
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PMID:Selenium enrichment of broccoli: interactions between selenium and secondary plant compounds. 1586 10

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

Colorectal cancer is the third most frequent fatal malignant neoplasm in the United States and is expected to cause significant morbidity and mortality. The recent recall of cyclooxygenase-2 inhibitors from clinical trials highlights the need to develop other agents for cancer chemoprevention trials. Intervention strategies with selenium compounds represent a viable option to reduce colon cancer. Here we discuss epidemiologic studies and ongoing clinical trials with selenium. In addition, we discuss preclinical mechanistic studies that provide insights into the biochemical and molecular bases for the anticancer effects of selenomethionine.
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PMID:Studies into the anticancer effects of selenomethionine against human colon cancer. 1638 40

As early as 1550 B.C., Egyptians realized the benefits of garlic as a remedy for a variety of diseases. Many epidemiological studies support the protective role of garlic and related allium foods against the development of certain human cancers. Natural garlic and garlic cultivated with selenium fertilization have been shown in laboratory animals to have protective roles in cancer prevention. Certain organoselenium compounds and their sulfur analogs have been identified in plants. Organoselenium compounds synthesized in our laboratory were compared with their sulfur analogs for chemopreventive efficacy. Diallyl selenide was at least 300-fold more effective than diallyl sulfide in protecting against 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary adenocarcinomas in rats. In addition, benzyl selenocyanate inhibited the development of DMBA-induced mammary adenocarcinomas and azoxymethane-induced colon cancer in rats and benzo[a]pyrene-induced forestomach tumors in mice. The sulfur analog, benzyl thiocyanate, had no effect under the same experimental conditions. Furthermore, we showed that 1,4-phenylenebis(methylene)selenocyanate, but not its sulfur analog, significantly inhibited DMBA-DNA adduct formation and suppressed DMBA-induced mammary carcinogenesis. Collectively, these results indicate that structurally distinctive organoselenium compounds are superior to their corresponding sulfur analogs in cancer chemoprevention. Additionally, synthetic aromatic selenocyanates are more effective cancer chemopreventive agents than the naturally occurring selenoamino acids. Because plants are capable of utilizing selenium in a manner similar to that in sulfur assimilation pathways, future studies should aim at determining whether, under appropriate conditions, these potent cancer chemopreventive synthetic selenium compounds can be synthesized by garlic and related allium foods.
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PMID:Cancer chemoprevention by garlic and garlic-containing sulfur and selenium compounds. 1648 82

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

While there is an increasing interest in selenium chemoprevention against human colon polyp recurrence and other cancers, the mechanism(s) by which these agents inhibit carcinogenesis are uncertain. Some of the proposed mechanisms include the inhibition of cytosine methyltransferases, carcinogen bioactivation, and inhibition of cyclooxygenase (COX). More recently, it has been suggested that selenium may exert growth inhibitory effects by activating p53. However, the molecular mechanisms of action of selenomethionine, an organoselenium compound present in selenized yeast and currently being investigated in human clinical trials for colon polyp prevention, are unclear. In the present study we tested the hypothesis that selenomethionine might affect colon cancer cell growth by p53 mediated apoptosis and/or cell cycle regulation. Four human colon cancer cell lines including HCT116 and RKO (wild type p53), HCT116-p53KO (isogenic control of HCT116 cells with p53 knocked out) and Caco-2 (mutant p53) were treated with 0-100 microM of selenomethionine for 24, 48 and 72 h. Cell viability rates were determined by the MTT assay. Cell cycle analysis was performed by flow cytometry and apoptosis measured by Annexin V-Cy5 staining. Expression of p53 protein was determined by Western blotting and immunofluorescence assays. All cell lines showed concentration and time dependent growth inhibition with selenomethionine, although HCT116 and RKO cells were the most sensitive to such treatments. Interestingly, although HCT116 and HCT116-p53KO are isogenic cell lines, selenomethionine caused a G2/M cell cycle arrest in HCT116 and RKO cells, but not in HCT116-p53KO cells. Similarly, both HCT116 and RKO demonstrated a significant increase in apoptosis (100-170%; p < 0.01) with 50-100 microM selenomethionine. Cell cycle arrest and apoptosis observed in HCT116 and RKO cell lines were accompanied by a marked increase in p53 protein expression following selenium treatment. These results clearly suggest that selenomethionine exerts p53 dependent growth inhibitory effects in colon cancer cells by inducing G2/M cell cycle arrest as well as apoptosis.
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PMID:Selenomethionine induces p53 mediated cell cycle arrest and apoptosis in human colon cancer cells. 1662 76


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