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

Low dietary intake of the essential trace element selenium can increase the risk of colon cancer. Utilizing RNA arbitrarily primed polymerase chain reaction (RAP-PCR), we sought to identify genes differentially expressed in HT29 human colon adenocarcinoma cells cultured with or without supplemental sodium selenite. One cDNA fragment, present at lower levels in samples from cells supplemented with selenite, had 97% nucleotide sequence identity with a sequence from the 3'-untranslated region of myc-associated zinc-finger protein (MAZ) cDNA. Northern blot analysis showed that steady-state levels of mRNA detected using this fragment as a probe were three times greater in unsupplemented (Se-) than in supplemented (Se+) samples. When a duplicate Northern blot was probed with a 300-bp fragment from the open reading frame of an MAZ cDNA clone, signal intensity was 2.2 times greater in Se- than in Se+ lanes. The MAZ protein has been shown to be a transcription regulator of the c-myc protooncogene. Signal intensity on a Northern blot probed with a segment of c-myc Exon 1 cDNA was 94% greater in Se- than in Se+ lanes. These findings are consistent with the established role for MAZ in regulating c-myc gene expression. They also suggest a molecular mechanism by which selenium intake may affect risk of colon cancer.
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PMID:Selenite supplementation decreases expression of MAZ in HT29 human colon adenocarcinoma cells. 884 23

The efficacy of dietary selenium supplementation is currently being evaluated in intervention trials. However, the biological mechanisms underlying the cancer chemopreventive effects of selenium supplementation have yet to be elucidated. Selenium metabolism and polyamine biosynthesis are linked in their common requirement for S-adenosylmethionine. Selenomethionine was the predominant form of selenium in the dietary supplement, therefore we evaluated the anti-tumorigenic effects of selenomethionine. We found that selenomethionine inhibited tumor growth (both in A549 lung and HT29 colon cancer cells) in a dose-dependent manner. At 24 and 72 h, polyamine content of A549 and HT29 cancer cell lines was decreased at doses that inhibited 50% of normal growth. Selenomethionine treatment induced apoptosis in both cancer cell lines. Exogenous spermine administration, which replenishes intracellular polyamine levels, prevented selenomethionine induced apoptosis. Selenomethionine administration to the cancer cell lines increased the number of cells in metaphase. This cell cycle effect appeared to be reversed with the co-administration of selenomethionine and spermine. These data suggested that at least part of the anti-carcinogenic effects of selenium supplementation might be due to a depletion in polyamine levels. This depletion of polyamines leads to an induction in apoptosis and perturbations in the cell cycle.
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PMID:Involvement of polyamines in selenomethionine induced apoptosis and mitotic alterations in human tumor cells. 921 3

GPX-GI is a cytosolic tetrameric Se-dependent glutathione peroxidase, similar in properties to GPX-1. Unlike the almost ubiquitous GPX-1, GPX-GI is mainly expressed in the epithelium of gastrointestinal tract. GPX-GI contributes to at least fifty percent of GPX activity in rodent small intestinal epithelium. The total GPX activity consists of at least 70% of selenium-dependent GPX activity in this compartment. By analyzing a panel of mouse interspecies DNA from the Jackson Laboratory's backcross resource, we mapped Gpx2 gene to mouse chromosome 12 between D12Mit4 and D12Mit5, near the Ccs1 locus which contains a colon cancer susceptibility gene. A pseudogene, Gpx2-ps is mapped to mouse chromosome 7. Comparison of Gpx2 gene expression in three pairs of C57BL/6Ha and ICR/Ha mice which are respectively resistant and sensitive to dimethylhydrazine-induced colon cancer, we found a higher Gpx2 mRNA level in C57BL/6Ha colon than ICR/Ha colon. Interestingly, a lower level of GPX activity is found in the resistant strain of mice. Because GPX-1 has three times higher specific activity than GPX-GI, our data suggest that the decreased GPX activity may result from a higher level of Gpx2 gene expression in those cells co-express Gpx1 gene.
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PMID:Expression and chromosomal mapping of mouse Gpx2 gene encoding the gastrointestinal form of glutathione peroxidase, GPX-GI. 931 6

This report reviews published epidemiologic research on the associations of vitamin and mineral supplementation with cancer risk. Although the literature on nutrition and cancer is vast, few reports to date have addressed supplemental nutrients directly (seven clinical trials, 16 cohort, and 36 case-control studies). These studies offer insight into effects of nutrients that are distinguishable from effects of other biologically active compounds in foods. Randomized clinical trials have not shown significant protective effects of beta-carotene, but have found protective effects of: alpha-tocopherol against prostate cancer; mixtures of retinol/zinc and beta-carotene/alpha-tocopherol/selenium against stomach cancer; and selenium against total, lung, and prostate cancers. Cohort studies provide little evidence that vitamin supplements are associated with cancer. Case-control studies have reported an inverse association between bladder cancer and vitamin C; oral/pharyngeal cancer and several supplemental vitamins; and several cancers and vitamin E. A randomized clinical trial, a cohort study, and a case-control study have all found inverse associations between colon cancer and vitamin E. Overall, there is modest evidence for protective effects of nutrients from supplements against several cancers. Future studies of supplement use and cancer appear warranted; however, methodologic problems that impair ability to assess supplement use and statistical modeling of the relation between cancer risk and supplement use need attention.
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PMID:Vitamin supplements and cancer risk: the epidemiologic evidence. 932 89

Selenium is an essential trace element, the deficiency of which is associated with an increased incidence of some human cancers. Dietary supplementation with selenium has been reported to produce a decrease in the incidence of some cancers in humans. Thioredoxin reductase (TR) is a newly discovered homodimeric selenocysteine (SeCys)-containing protein that catalyzes the NADPH-dependent reduction of the redox protein thioredoxin (Trx). Trx is overexpressed by a number of human tumors, and experimental studies have shown that Trx contributes to the growth and to the transformed phenotype of some human cancer cells. Thus, TR, by reducing Trx, could play a role in regulating the growth of normal and cancer cells. We have investigated mechanisms by which selenium, in the form of sodium selenite, added to serum-free growth medium regulates TR activity in cancer cell lines. Selenium caused a dose-dependent increase in cellular TR activity. The increase in TR activity produced by 1 microM Se compared to medium with no added selenium was: for MCF-7 breast cancer cells, 37-fold; for HT-29 colon cancer cells, 19-fold; and for A549 lung cancer cells, 8-fold. In contrast, Jurkat and HL-60 leukemia cells showed no increase in TR activity. The half-life of the time course of induction of TR in HT-29 cells after adding selenium was 10 h. The increase in TR activity was accompanied by an increase in TR protein levels up to 3-fold and an increase in the specific activity of the enzyme of 5-32-fold, depending on the cell line. Studies using 75Se showed that the amount of selenium incorporated into TR increased with increasing selenium concentration up to a ratio of 1 selenium per TR monomer. There was an increase in TR mRNA levels of 2-5-fold at 1 microM selenium and an increase in the stability of TR mRNA with a half-life for degradation of 21 h compared to 10 h in the absence of selenium. Trx mRNA and protein levels and Trx mRNA stability were not affected by selenium. The results of the study show that the increase in TR activity caused by selenium is specific and due to several effects, including an increase in the stability of TR mRNA leading to increased TR mRNA levels, an increase in TR protein, but predominantly to an increase in the specific activity of TR associated with increased incorporation of selenium into the enzyme.
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PMID:Mechanisms of the regulation of thioredoxin reductase activity in cancer cells by the chemopreventive agent selenium. 935 64

Selenium (Se) is an essential trace element and has been reported to decrease the incidence of some human cancers. We have investigated the effects of Se on thioredoxin reductase, a selenocysteine containing flavoenzyme, in HT-29 human colon cancer cells grown in serum-free medium. Sodium selenite and other Se containing compounds produced a time and concentration dependent increase in intracellular thioredoxin reductase activity and protein levels. Selenite was the most active of the Se compounds examined: 1 microM selenite produced a 28-fold increase in thioredoxin reductase activity by 1 day and 10 microM selenite over a 60-fold increase by 5 days. The activity of a related non-selenocysteine containing flavoenzyme glutathione reductase was not increased by selenite. Selenite, but not the other Se containing compounds inhibited cell growth at concentrations above 2 microM. The results show that Se can produce large increases in cell thioredoxin reductase activity.
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PMID:Cellular thioredoxin reductase activity is regulated by selenium. 941 75

Plasma selenium concentration was assessed in 44 patients with cancer of the gastrointestinal tract (19 subjects with stomach cancer and 25 with colon cancer) and 25 age-matched healthy control subjects. Selenium concentration was determined by the fluorometric method. The observed plasma selenium concentrations in gastrointestinal cancer patients (37.0 +/- 11.05 ng Se/ml or 38.4 +/- 12.6 ng Se/ml in stomach or colon cancer patients, respectively) were significantly lower as compared to the healthy age-matched control group (51.4 +/- 14.4 ng Se/ml). The diagnosed low selenium status may be considered as a high risk for cancer development.
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PMID:Plasma selenium concentration in patients with stomach and colon cancer in the Upper Silesia. 960 14

Observational, clinical and experimental studies have suggested that dietary supplementation with selenium can inhibit the development of colon cancer. Since toxicity and chemopreventive efficacy of selenium compounds depend to a large extent, on the form of selenium the development of efficacious organoselenium compounds with low toxicity is being pursued in our laboratory. We have assessed the chemopreventive properties of a newly synthesized organoselenium compound, benzyl selenocyanate glutathione conjugate (BSeSG), and of benzyl selenocyanate (BSC), as a positive control, using azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) as a measure of efficacy. Five-week-old male F344 rats were fed the control diet (modified AIN-76A) or experimental diets containing 10 or 20 ppm BSeSG (1.7 and 3.4 ppm as Se, respectively), or 10 ppm BSC (4.1 ppm as Se). One week later, all animals except those in vehicle (normal saline)-treated groups were s.c. injected with AOM (15 mg/kg of body weight, once weekly for 2 weeks). All animals were sacrificed 7 weeks after the last AOM injection, and the ACF, levels of prostaglandin E2 (PGE2), cyclooxygenase protein expression (COX-1 and -2), and glutathione S-transferase type mu (GST-mu) were determined in the colon. As expected, dietary administration of BSC suppressed ACF development by about 37%. In rats administered 10 or 20 ppm BSeSG, the frequencies of AOM-induced colonic ACF were significantly decreased compared to those of rats given AOM and control diet by about 41% (P<0.01) and 61% (P<0.001), respectively. Administration of BSeSG inhibited PGE2 production (81-88% inhibition) via COX-2 synthesis in the colonic mucosa (18-60% inhibition). Also, BSeSG increased GST-mu protein activity in colonic mucosa (30-32% increase). These data suggest that a newly synthesized organoselenium compound, BSeSG might be a promising chemopreventive agent against colon carcinogenesis.
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PMID:Evaluation of benzyl selenocyanate glutathione conjugate for potential chemopreventive properties in colon carcinogenesis. 962

There is strong evidence that selenium protects against certain human cancers, but the underlying mechanism is unknown. Glutathione peroxidase (GPX1) and thioredoxin reductase (TR), the most abundant antioxidant selenium-containing proteins in mammals, have been implicated in this protection. We analyzed the expression of TR and GPX1 in the following model cancer systems: (1) liver tumors in TGFalpha/c-myc transgenic mice; (2) human prostate cell lines from normal and cancer tissues; and (3) p53-induced apoptosis in a human colon cancer cell line. TR was induced while GPX1 was repressed in malignancies relative to controls in transgenic mice and prostate cell lines. In the colon cell line, p53 expression resulted in elevated GPX1, but repressed TR. The data indicate that TR and GPX1 are regulated in a contrasting manner in the cancer systems tested and reveal the p53-dependent regulation of selenoprotein expression. The data suggest that additional studies on selenoprotein regulation in different cancers are required to evaluate future implementation of selenium as a dietary supplement in individuals at risk for developing certain cancers.
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PMID:Contrasting patterns of regulation of the antioxidant selenoproteins, thioredoxin reductase, and glutathione peroxidase, in cancer cells. 979 1

There is increasing evidence that selenium can protect against tumorigenesis or preneoplastic lesion development induced by chemical carcinogens. This study examined whether selenite, selenate or selenomethionine would be protective against 3, 2'-dimethyl-4-aminobiphenyl (DMABP)-DNA adduct formation in the liver and colon of rats and sought to delineate the mechanism for the protective effects of the different chemical forms of selenium against aberrant crypt formation, a preneoplastic lesion for colon cancer. After injection of DMABP, two DNA adducts were identified in the liver and colon of rats. Supplementation with either 0.1 or 2.0 mg selenium/kg diet as either selenite or selenate but not selenomethionine resulted in significantly fewer (53-70%; P < 0.05) N-(deoxyguanosin-8-yl)-(deoxyguanosin-8-yl)-3, 2'-dimethyl-4-aminobiphenyl (C8-DMABP)-DNA adducts in the colon but not the liver than in rats fed a selenium-deficient diet. Rats supplemented with selenomethionine had greater (P < 0.05) plasma and liver selenium concentrations and glutathione peroxidase activity than those supplemented with selenite or selenate; however, they also had more DMABP-DNA adducts. The protective effect of selenite and selenate against DMABP-DNA adduct formation apparently is not a result of alterations in plasma or liver selenium concentrations or altered glutathione peroxidase or glutathione transferase activities but may be related to differences in the metabolism of the different forms of selenium.
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PMID:The chemical form of selenium influences 3,2'-dimethyl-4-aminobiphenyl-DNA adduct formation in rat colon. 991 77


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