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)

Selenomethionine (SeMet), an organic selenium compound, has been demonstrated to have significant chemopreventive activity. However, the mechanism of action of SeMet has yet to be identified. Previously, our laboratory found that treatment of cells with SeMet induced apoptosis and altered the cell cycle. These observations have led to further analysis of the cell cycle effects of SeMet in colon cancer cells. Synchronized HCT 116 colon cancer cells treated with 100 microM SeMet for 66 h were found to have a transient delay in G2/M phase of the cell cycle at 18 and 24 h after treatment. With this was observed an inhibition of cell growth. Coincidentally with this delay was a decrease in mitotic cyclin B RNA expression at 18 h after treatment. In addition, the cdc2 kinase activity of HCT 116 cells was decreased at 18 h. Morphological studies indicate an increase in the number of treated cells (45%) undergoing apoptosis at 66 h compared to control cells (27%). These studies demonstrate that modulation of mitotic cyclin expression and cdc2 kinase activity play a role in the ability of SeMet to inhibit tumor cell growth. A consequence of this prolonged arrest is apoptosis.
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PMID:Inhibition of mitotic cyclin B and cdc2 kinase activity by selenomethionine in synchronized colon cancer cells. 1127 85

Selenium (Se) from high-Se garlic reduces the incidence of chemically induced mammary tumors, and Se from high-Se broccoli reduces colon cancer. However, the ability of Se from high-Se broccoli to protect against mammary cancer has not been tested. Also, the sprout form of broccoli contains many secondary plant compounds that are known to reduce cancer risk, but the anticarcinogenic activity of broccoli sprouts has not been investigated. The present studies examined the ability of high-Se broccoli or high-Se broccoli sprouts to protect against chemically induced mammary or colon cancer. In one experiment, Sprague--Dawley rats that consumed diets containing 3.0 microg of Se/g supplied as high-Se broccoli had significantly fewer mammary tumors than rats fed 0.1 microg of Se as selenite with or without the addition of regular broccoli. In the second experiment, Fisher F-344 rats fed 2.0 microg of Se/g of diet supplied as either high-Se broccoli florets or high-Se broccoli sprouts had significantly fewer aberrant colon crypts than rats fed 0.1 or 2 microg of Se/g of diet supplied as selenite with or without the addition of low-Se broccoli. These data demonstrate that the cancer-protective effect of Se in high-Se broccoli extends to mammary cancer and the protective forms of broccoli against colon cancer include high-Se broccoli sprouts.
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PMID:Cancer-protective properties of high-selenium broccoli. 1136 55

The reduction in incidence of chemically-induced colon cancer by foods high in selenium (Se) was investigated in Fisher-344 rats. The foods used were high-Se broccoli (produced in a greenhouse by addition of selenate to the media surrounding the plant roots) and a processed high-Se wheat product (made by milling high-Se wheat purchased from a seleniferous area). Weanling rats were fed diets containing different amounts of Se from these foods or from selenium salts (selenite and selenate). Early in the experiment the animals were injected with a chemical carcinogen. After 11 weeks on diets animals were killed and the colons examined for preneoplastic lesions (aberrant crypts foci, ACF). ACF were significantly reduced in animals fed supra-nutritional amounts of Se from broccoli, despite the finding that Se from broccoli was poorly bioavailable. Supra-nutritional amounts of Se from high-Se processed wheat also significantly reduced aberrant crypts (AC), although pure selenomethionine, (the predominant chemical form of Se in wheat), did not significantly reduce AC. These results emphasize the need to study Se in food forms, and not extrapolate from previous studies using pure chemical forms in cancer inhibition studies. They also demonstrate that foods with high Se bioavailability are not necessarily the most efficacious for cancer incidence reduction.
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PMID:Selenium (Se) from high-selenium broccoli is utilized differently than selenite, selenate and selenomethionine, but is more effective in inhibiting colon carcinogenesis. 1156 56

Multiple intestinal neoplasia (Min) mice are a good model for the investigation of the effects of dietary alterations in a genetic model for intestinal cancer. Previous studies have shown that selenium-enriched broccoli is protective against chemically induced colon cancer susceptibility. This study investigated whether selenium-enriched broccoli would be protective against intestinal cancer susceptibility in Min mice. Five-week-old heterozygotic male Min mice were fed an AIN-93-based diet containing either low-selenium broccoli or an equivalent amount of high-selenium broccoli for 10 wk. Mice fed the selenium-enriched broccoli had fewer (P < 0.02) small intestinal (46.4 +/- 3.7 vs. 65.6 +/- 6.1) and large intestinal (0.43 +/- 0.17 vs. 1.93 +/- 0.27) tumors than those fed an equivalent amount of unenriched broccoli. Min mice fed the selenium-enriched broccoli had small but significant (P < 0.0001) increases in plasma and liver selenium concentrations and red blood cell glutathione peroxidase activity. These results extend previous observations that selenium-enriched broccoli is protective against chemically induced mammary and colon cancer in rats.
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PMID:Selenium-enriched broccoli decreases intestinal tumorigenesis in multiple intestinal neoplasia mice. 1182 96

Selenium and vitamin E are probably 2 of the most popular dietary supplements considered for use in the reduction of prostate cancer risk. This enthusiasm is reflected in the initiation of the Selenium and Vitamin E Chemoprevention Trial (SELECT). Is there sufficient evidence to support the use of these supplements in a large-scale prospective trial for patients who want to reduce the risk of prostate cancer? Results from numerous laboratory and observational studies support the use of these supplements, and data from recent prospective trials also add partial support. However, a closer analysis of the data reveals some interesting and unique associations. Selenium supplements provided a benefit only for those individuals who had lower levels of baseline plasma selenium. Other subjects, with normal or higher levels, did not benefit and may have an increased risk for prostate cancer. The concept that supplements reduce prostate cancer risk only in those at a higher risk and/or those with lower plasma levels of these compounds is supported by trials examining beta-carotene supplements. Smokers may be the only individuals who benefit, as has also been shown with vitamin E supplementation. In 4 recent prospective studies, vitamin E was found to reduce the risk of prostate cancer in past/recent and current smokers and those with low levels of this vitamin. Vitamin E supplements in higher doses (> or =100 IU) were also associated with a higher risk of aggressive or fatal prostate cancer in nonsmokers from a past prospective study. The dose of vitamin E in the SELECT trial (400 IU/day) is 8 times higher than what has been suggested to be effective (50 IU/day) by the largest randomized prospective trial in which the incidence rate of prostate cancer was used as an endpoint. Recent research also suggests that dietary vitamin E may be associated with a lower risk of prostate cancer than the vitamin E supplement. Additionally, recent results from all past cardiovascular prospective, randomized trials suggest that vitamin E shows little benefit for cardiovascular disease risk, especially at the dose being used in the SELECT trial. Other intriguing positive findings from past prospective studies of supplements suggest that aspirin and other nonsteroidal anti-inflammatory drugs have a role in reducing the risk of prostate cancer or other types of cancer (eg, colon cancer). It may be time to conduct a large costly trial to reconsider the use of selenium and vitamin E supplements for the reduction of prostate cancer risk. Some evidence for the use of these supplements exists, but serious embellishment of study findings may be leading to an inappropriate use of these supplements in a clinical setting.
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PMID:Selenium and vitamin E supplements for prostate cancer: evidence or embellishment? 1193 32

Currently, selenium (in the form of high selenium containing yeast or selenomethionine) is being evaluated for anticancer effects against both human colon polyp recurrence and human prostate cancer, respectively. Chemical speciation analysis of the high selenium containing yeast indicates that selenomethionine (SeMet) is a major constituent of selenized yeast. We tested the hypothesis that SeMet might affect colon cancer cell growth by mechanisms involving cyclooxygenases (COX). The growth of all four-colon cancer cell lines tested was inhibited by selenomethionine. Furthermore, selenomethionine decreased COX-2 protein and PGE2 levels in HCA-7 cells. Selenomethionine suppressed COX-2 RNA levels in HCA-7 cells which could account for decreased COX-2 protein levels. Finally, the addition of PGE2 protected cells from the antiproliferative effects of selenomethionine in a concentration dependent manner. Selenomethionine might regulate COX-2 at the transcriptional level. These data suggests that Se-Met-induced cell growth inhibition may be, in part, mediated by COX-2 dependent mechanisms. The results of this study support the use of selenium agents in colon cancer chemoprevention trials.
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PMID:Selenomethionine inhibits growth and suppresses cyclooxygenase-2 (COX-2) protein expression in human colon cancer cell lines. 1243 49

Multiple intestinal neoplasia (Min) mice are a good model for investigating the effects of dietary alterations in a genetic model for intestinal cancer. Previous studies have shown that selenium-enriched broccoli effectively reduces colon cancer susceptibility. Although colon cancer cells mainly metastasize to the liver, little is known about the effects of selenium-enriched broccoli on gene expression in mouse liver. To better understand the protective role for selenium-enriched broccoli in tumorigenesis, a gene profile of the mouse liver was analyzed. Mice were fed either 0.11 mg selenium/kg control diet or 2.1 mg selenium/kg selenobroccoli diets for 10 weeks. Use of mouse pathway finder-1 GEArrays revealed that selenium-enriched broccoli moderately increased ikBalphakappaB, hsp86, gadd45 gene transcripts. In addition, analysis of the binding of liver nuclear proteins to (32)P-labeled probes demonstrated that selenium-enriched broccoli enhanced the binding of transcription factor p53, NFkappaB, AP-1 to their cis-acting elements. Collectively, these results suggest for the first time that selenium-enriched broccoli activates certain pro-apoptotic genes linked to p53, NFkappaB and stress signal pathways in response to "danger signals" such as tumorigenesis.
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PMID:Effect of selenium-enriched broccoli diet on differential gene expression in min mouse liver(1,2). 1277 Jun 47

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

Selenoproteins such as glutathione peroxidases (GPx), thioredoxin reductases (TrxR), and selenoprotein P (SePP) contain molecular selenium in form of selenocysteines within their active center. They are involved in the defense of reactive oxygen species, which otherwise may cause DNA damage and alterations of protein function. Selenium intake has been linked to colon carcinogenesis in epidemiological and interventional studies. In a double-blinded, placebo-controlled trial, we demonstrate that carriers of colon adenomas present with low basal serum levels of selenium and plasma glutathione peroxidase (pGPx) activity before treatment, but both parameters can be normalized by interventional selenium supplementation. GPx activity in colon mucosa was enhanced in the verum group, albeit this had only borderline significance. No change of activity was observed for mucosal TrxR activity on selenium supplementation. In summary, our results confirm the existence of low selenium levels in patients prone to colon adenomas and show that by selenium supplementation this can be normalized. If prospective trials confirm that selenium supplementation reduces colon cancer incidence rates, it may be concluded that selenium supplementation should be recommended for patients at risk.
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PMID:Selenium supplementation enhances low selenium levels and stimulates glutathione peroxidase activity in peripheral blood and distal colon mucosa in past and present carriers of colon adenomas. 1469 Jul 87

Many of the cancers common in the Western world, including colon, prostate and breast cancers, are thought to relate to dietary habits. Of the known risk factors, many will act through increasing the probability of mutation. Recognised dietary mutagens include cooked meat compounds, N-nitroso compounds and fungal toxins, while high meat and saturated fat consumption, increasing rates of obesity, and regular consumption of alcohol and tobacco are all dietary trends that could indirectly enhance the probability of mutation. However, there are significant difficulties in implementing and sustaining major dietary changes necessary to reduce the population's intake of dietary mutagens. Dietary antimutagens may provide a means of slowing progression toward cancer, and be more acceptable to the population. Consideration of genetic mechanisms in cancer development suggest several distinct targets for intervention. Strategies that reduce mutagen uptake may be the most simple intervention, and the one least likely to result in undesirable side effects. Certain (but not all) types of dietary fibres appear to reduce mutation through this mechanism, as may certain probiotics and large planar molecules such as chlorophyllin. Antioxidants have been suggested to scavenge free radicals, and prevent their interactions with cellular DNA. Small molecule dietary antioxidants include ascorbic acid, Vitamin E, glutathione, various polyphenols and carotenoids. We found a statistically significant relationship between colon cancer incidence and soil selenium status across different regions of New Zealand. Additionally, a study of middle-aged men suggested that blood selenium levels lower than 100 ng/ml were inadequate for repair or surveillance of oxidative (and other) DNA damage. We suggest that selenium will be an important antimutagen, at least in New Zealand, possibly through antioxidant effects associated with selenium's role in enzymes associated with endogenous repair of DNA damage. Modulation of xenobiotic metabolizing enzymes is well recognised as cancer-protective, and is a property of various flavonoids and a number of sulfur-containing compounds. Many fruits and vegetables contain compounds that will protect against mutation and cancer by several mechanisms. For example, kiwifruit has antioxidant effects and may also affect DNA repair enzymes. Dietary folate may be a key factor in maintenance of methylation status, while enhanced overall levels of vitamins and minerals may retard the development of genomic instability. The combination of each of these factors could provide a sustainable intervention that might usefully delay the development of cancer in New Zealand and other populations. Although there are a range of potentially antimutagenic fruits, vegetables and cereals available to these populations, current intake is generally below the level necessary to protect from dietary or endogenous mutagens. Dietary supplementation may provide an alternative approach.
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PMID:Dietary cancer and prevention using antimutagens. 1513 38


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