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)

N-Nitrosamines formed by nitrosation of heterocyclic amines might initiate colon cancer in individuals consuming well-done red meat diets and with inflammatory conditions in their colon. This study investigates nitric oxide (NO)-mediated nitrosation of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and the influence of dietary (hemin) and inflammatory [NO, myeloperoxidase (MPO), and H(2)O(2)] components on nitrosation. Using the NO donor spermine NONOate (1.2 microM NO/min) at pH 7.4 with 0.005 mM MeIQx, a product due to NO autoxidation was at the limit of detection (1% of total radioactivity recovered by HPLC). Product formation increased 13- or 16-fold in the presence of 10 microM hemin or 85 nM MPO, respectively, with an in situ system for generating H(2)O(2) (glucose oxidase/glucose). The nitrosation product and its chloro derivative were analyzed by electrospray ionization mass spectrometry, and the product was determined to be 2-nitrosoamino-3,8-dimethylimidazo[4,5-f]quinoxaline (N-NO-MeIQx). Nitrosation by NO autoxidation was only detected at > or =1.2 microM NO/min and was not affected by H(2)O(2). Investigations with hemin determined minimum effective components necessary for potentiation: 1 microM hemin, 1 microM H(2)O(2)/min, and 0.012 microM NO/min. The reactive nitrogen oxygen species (RNOS) produced by hemin and MPO had a 4- and 3-fold, respectively, greater affinity for MeIQx than those produced by NO autoxidation. Test agents were used to characterize nitrosation. Results with catalase, SOD, azide, and NADH are consistent with multiple RNOS, the lack of peroxynitrite involvement in nitrosation, and peroxidatic potentiation by oxidative nitrosylation rather than nitrosation. Using phorbol ester stimulated human neutrophils, the formation of N-NO-MeIQx and its modification by test agents was consistent with MPO and not peroxynitrite. Thus, nitrosation of MeIQx and its potentiation by hemin and MPO provide a mechanism by which well-done red meat consumption and inflammation can generate N-nitroso compounds and initiate colon cancer under inflammatory conditions, such as colitis.
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PMID:Nitric oxide-mediated nitrosation of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline potentiated by hemin and myeloperoxidase. 1596 39

Human alteration of the nitrogen cycle has resulted in steadily accumulating nitrate in our water resources. The U.S. maximum contaminant level and World Health Organization guidelines for nitrate in drinking water were promulgated to protect infants from developing methemoglobinemia, an acute condition. Some scientists have recently suggested that the regulatory limit for nitrate is overly conservative; however, they have not thoroughly considered chronic health outcomes. In August 2004, a symposium on drinking-water nitrate and health was held at the International Society for Environmental Epidemiology meeting to evaluate nitrate exposures and associated health effects in relation to the current regulatory limit. The contribution of drinking-water nitrate toward endogenous formation of N-nitroso compounds was evaluated with a focus toward identifying subpopulations with increased rates of nitrosation. Adverse health effects may be the result of a complex interaction of the amount of nitrate ingested, the concomitant ingestion of nitrosation cofactors and precursors, and specific medical conditions that increase nitrosation. Workshop participants concluded that more experimental studies are needed and that a particularly fruitful approach may be to conduct epidemiologic studies among susceptible subgroups with increased endogenous nitrosation. The few epidemiologic studies that have evaluated intake of nitrosation precursors and/or nitrosation inhibitors have observed elevated risks for colon cancer and neural tube defects associated with drinking-water nitrate concentrations below the regulatory limit. The role of drinking-water nitrate exposure as a risk factor for specific cancers, reproductive outcomes, and other chronic health effects must be studied more thoroughly before changes to the regulatory level for nitrate in drinking water can be considered.
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PMID:Workgroup report: Drinking-water nitrate and health--recent findings and research needs. 1688 7

c-Src is a non-receptor tyrosine kinase which plays a significant role in the growth mediated signaling pathway impacting cellular proliferation, differentiation, mobility, survival and transformation. Myristoylation of pp60(c-src) leads to its membrane association and activation, a process catalyzed by N-myristoyltransferase (NMT). We have shown earlier increased NMT activity in the early stages of colon cancer. A novel sulfur nitrogen donor ligand and its Cu(II) and Mn(III) complexes have been prepared and characterized using various physicochemical analyses. These Cu(II) and Mn(III) complexes showed cytotoxicity against the colon cancer cell line HT29. The IC(50) for Cu(II) and Mn(III) complexes were 12.2 and 16.1 microM, respectively. HT29 cells treated with Cu(II) and Mn(III) complexes induced apoptosis and inhibited endogenous NMT activity. Furthermore, they induced higher levels of hsc70 and inhibited the expression of c-Src. Inhibition of endogenous NMT activity by metal complexes was demonstrated for the first time. This study also suggested that NMT activity is crucial for cell survival and demonstrated that cessation in activity results in apoptosis. These metal complexes may prove to be novel therapeutic agents for cancer targeting NMT.
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PMID:Copper(II) and manganese(III) complexes of N'-[(2-hydroxy phenyl) carbonothioyl] pyridine-2-carbohydrazide: novel therapeutic agents for cancer. 1660 Apr 65

Bisnaphthalimidopropyl derivatives (BNIPSpd, BNIPDaoct, BNIPDanon, BNIPDadec, BNIPDpta and BNIPDeta) were synthesised in yields ranging from 50% to 70% and their cytotoxicity against colon cancer cells (Caco-2) and the parasite Leishmania infantum determined using the MTT assay. Cytotoxicity within Caco-2 cells was manifested with IC(50) values between 0.3 and 22 microM. Compounds with the central longer alkyl chains exhibited the highest cytotoxicity. Against L. infantum, IC(50) values were encompassed within a narrower concentration range of 0.47-1.54 microM. In the parasites, the presence of nitrogen in the central chain and the length of the central alkyl chains did not especially enhance cytotoxicity. This may be due to the way these compounds are transported in the cells.
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PMID:The synthesis and the in vitro cytotoxicity studies of bisnaphthalimidopropyl polyamine derivatives against colon cancer cells and parasite Leishmania infantum. 1701 Jun 16

The relationship between nitrate levels in drinking water and colon cancer has been inconclusive. A matched case-control and a nitrate ecology study were used to investigate the association between colon cancer mortality and nitrate exposure from Taiwan's drinking water. All colon cancer deaths of Taiwan residents from 1999 through 2003 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair matched to the cases by sex, year-of-birth, and year-of-death. Each matched control was selected randomly from the set of possible controls for each case. Data on nitrate-nitrogen (NO3-N) level of drinking water throughout Taiwan have been collected from Taiwan Water Supply Corporation (TWSC). The municipality of residence for cases and controls was assumed to be the source of the subject's nitrate exposure via drinking water. The adjusted odds ratios for colon cancer death for those with high NO3-N levels in their drinking water, as compared to the lowest tertile, were 0.98 (0.84-1.14) and 0.98 (0.83-1.16), respectively. The results of the present study show that there was no statistically significant association between NO3-N in drinking water at levels in this study and risk of death from colon cancer.
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PMID:Nitrate in drinking water and risk of death from colon cancer in Taiwan. 1731 4

Cisplatin is one of the most effective chemotherapeutic agents and plays a major role in the treatment of a variety of human solid tumors. However, its toxicity limits the clinical use. Recently, the administration of antioxidants has been suggested to protect against cisplatin-induced nephrotoxicity. The present study was designed to estimate the antitumor activity of the licorice extract alone and in combination with cisplatin, and its protective potential against cisplatin-induced toxicity in a mouse xenograft model. The administration of the licorice extract significantly inhibited tumor growth in BALB/C mice inoculated with CT-26 colon cancer cells. The combination of the licorice extract and cisplatin diminished the therapeutic efficacy of cisplatin but promoted considerably antitumor activity of the licorice extract. In mice with cisplatin treatment for 15 d, the serum levels of blood urea nitrogen and creatinine remarkably were increased by kidney damage, and the serum alanine aminotransferase and aspartate aminotransferase levels were elevated by liver damage. The administration of the licorice extract plus cisplatin recovered these functional indices in the kidney and liver to almost the control levels. In addition, the administration of the licorice extract significantly reduced the cisplatin-induced oxidative stress. Taken together, the administration of the licorice extract inhibits the growth of mouse colon carcinoma without any adverse effects, and reduces the cisplatin-induced toxicity. Therefore, the licorice extract may be a candidate for an anticancer and chemopreventive agent. However, cancer patients with cisplatin therapy should avoid the supplementation of the licorice extract.
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PMID:Effects of the licorice extract against tumor growth and cisplatin-induced toxicity in a mouse xenograft model of colon cancer. 1797 99

The goal of this study was to identify systematic alterations in key cell signaling and metabolic pathways that occur during colon cancer carcinogenesis and metastasis. Understanding gene expression changes in the context of specific pathways may increase our understanding of carcinogenesis and help guide treatment. Ten cases, with matched controls, were profiled for expression of >18,000 human transcripts using Affymetrix U133A chips. Data were filtered using GeneSifter. Gene expression levels for primary colon samples were compared to a normal colon while metastatic tissues were compared to the primary colon. Differentially regulated genes were associated using the Kyoto encyclopedia of genes and genome pathways to identify cell signaling and metabolic pathways altered during carcinogenesis and metastasis. Primary colon samples displayed high positive z-scores (indicating a gene ontology term that occurs more frequently than expected) for genes involved in Wnt-signaling (4.11), nitrogen metabolism (7.30) and inositol phosphate metabolism (2.47). Expression level changes for individual genes in each cluster were statistically significant (e.g. p=0.017 for cyclin D1 in the Wnt-signaling cluster). Metastatic tissue from the liver and omentum, but not the lung, displayed a decreased expression of genes important for oxidative phosphorylation. The metastatic tissue from all sites displayed a substantially decreased expression for genes involved in butanoate and propanoate metabolism and valine, leucine and isoleucine degradation. Our results demonstrate that systematic changes in gene expression occur for proteins involved in key cell signaling and metabolic pathways during the course of carcinogenesis and metastasis. These expression level changes complement the spectrum of mutations that characterize the progression of colorectal cancer.
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PMID:Tissue-dependent and -independent gene expression changes in metastatic colon cancer. 1809 2

A growing amount of attention has been focused on the investigation of the effects of chemopreventive agents on the inhibition of cancer cell growth and toxicity in combination with chemotherapeutics. The objective of this study was to determine whether isoliquiritigenin (ISL) has the potential to serve as a beneficial supplement during cisplatin chemotherapy. We found that the administration of ISL alone significantly reduced the size of the solid tumors in CT-26 cell-inoculated BALB/c mice, without any detectable induction of nephrotoxicity, hepatotoxicity, and oxidative stress, and ISL reduced the viability and DNA synthesis of CT-26 murine colon cancer cells in a dose-dependent manner. ISL did not affect the therapeutic efficacy of cisplatin. Furthermore, ISL suppressed cisplatin-induced kidney damage characterized by increases in serum creatinine and blood urea nitrogen, as well as cisplatin-induced liver damage characterized by increases in serum alanine aminotransferase and aspartate aminotransferase. The repeated oral administration of ISL prior to cisplatin treatment exerted a preventive effect on cisplatin-mediated increases in serum nitric oxide and tissue lipid peroxidation levels, and it recovered depleted GSH levels in the tissues. Therefore, supplementation with ISL may be an effective approach to counteracting the side effects of cisplatin therapy in cancer patients.
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PMID:Isoliquiritigenin inhibits tumor growth and protects the kidney and liver against chemotherapy-induced toxicity in a mouse xenograft model of colon carcinoma. 1836 95

Although chemotherapy has an important function in the treatment of most solid tumours, its clinical applications are limited by severe side effects such as nephrotoxicity, hepatotoxicity, ototoxicity and neurotoxicity. Recently, a growing amount of attention has been focused on the investigation of the effects of chemopreventive agents on the inhibition of cancer cell growth and toxicity in combination with chemotherapeutics. The aim of this study was to determine whether licochalcone A (LCA) has the potential to serve as a beneficial supplement during cisplatin chemotherapy. We found that the administration of LCA alone significantly inhibited the size of the solid tumours in CT-26 cell-inoculated Balb/c mice, without any detectable induction of nephrotoxicity, hepatotoxicity and oxidative stress. LCA also suppressed cell proliferation by reducing DNA synthesis of CT-26 murine colon cancer cells in a dose-dependent manner. LCA did not affect the therapeutic efficacy of cisplatin. Furthermore, LCA inhibited the cisplatin-induced kidney damage characterized by increases in the serum creatinine and blood urea nitrogen, as well as the cisplatin-induced liver damage characterized by increases in the serum alanine aminotransferase and aspartate aminotransferase. The repeated oral administration of LCA prior to cisplatin treatment exerted a preventive effect on the cisplatin-mediated increases in the serum nitric oxide and the tissue lipid peroxidation levels, and recovered the depleted reduced glutathione levels in the tissues. These results suggest that supplementation with LCA may be beneficial in counteracting the side effects of cisplatin therapy in cancer patients.
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PMID:Licochalcone A inhibits the growth of colon carcinoma and attenuates cisplatin-induced toxicity without a loss of chemotherapeutic efficacy in mice. 1848 61

Anticancer agents act, at least in part, by inducing reactive oxygen and nitrogen species (RONS). We examined the redox effect on SW480 and HT-29 colon cancer cells of four anticancer compounds, arsenic trioxide, phosphoaspirin, phosphosulindac, and nitric oxide-donating aspirin (NO-ASA). All compounds inhibited the growth of both cell lines (IC(50), 10-90 micromol/L) and induced RONS detected by a general RONS molecular probe. NO-ASA, which induced at least four individual RONS (NO, H(2)O(2), superoxide anion, and peroxynitirte), induced apoptotic and necrotic cell death that was RONS-mediated (cell death paralleled RONS levels and was abrogated by N-acetyl cysteine but not by diphenylene iodonium, which displayed prooxidant activity and enhanced cell death). Nuclear factor-kappaB and mitogen-activated protein kinases were modulated by RONS. Thioredoxin-1 (Trx-1), an oxidoreductase involved in redox regulation, was heavily oxidized in response to RONS and mediated the growth inhibitory effect of the anticancer agents; knocking-down trx-1 expression by small interfering RNA abrogated cell death induced by them. These compounds also inhibited the activity of Trx reductase that reduces oxidized Trx-1, whereas the Trx reductase inhibitor aurothiomalate synergized with NO-ASA in the induction of cell death. Our findings indicate that the Trx system mediates to a large extent redox-induced cell death in response to anticancer agents. This mechanism of action may be shared by more anticancer agents and deserves further assessment as a candidate mechanism for the pharmacologic control of cancer.
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PMID:The thioredoxin system mediates redox-induced cell death in human colon cancer cells: implications for the mechanism of action of anticancer agents. 1892 98


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