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

Increased risk for development of colon cancer is associated with red meat intake and iron toxicity is discussed for one underlying mechanism. Anyhow, for iron itself only limited evidence is found. In this study, effects of different iron compounds on proliferation of HT29 carcinoma and LT97 adenoma human colon cells were investigated. After treatment of cells with inorganic (ferrous sulfate: FeSO4 and ferric nitrilotriacetate: FeNTA) and organic (hemoglobin and hemin) iron sources (24-72 h), number of cells and metabolic activity were measured. Under normal cell culture conditions, neither iron compound elevated cell growth in either cell line with the exception of FeNTA which induced LT97 cell growth significantly. Distinct inhibition of cell proliferation was measured for organic iron. Serum-free incubation of HT29 cells revealed growth promoting properties of iron under deficiency. Even though organic iron, especially hemin, was a potent growth factor, both substances showed also dose-dependent cytotoxic effects. In conclusion, these data emphasize that not iron itself, but merely organic iron may promote carcinogenic events. Since promotion of proliferation was only detectable under deficiency, cytotoxic properties of organic iron may be of more importance in colon carcinogenesis.
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PMID:Influence of inorganic and organic iron compounds on parameters of cell growth and survival in human colon cells. 1944 23

Bile acid-polyaminocarboxylate conjugates containing NE3TA, a potential iron chelator displayed significant cytotoxicities in both HeLa and HT29 colon cancer cells, and cholic acid-NE3TA attached to an organic fluorophore was shown to enter the HT29 cancer cells.
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PMID:Bile acid-based polyaminocarboxylate conjugates as targeted antitumor agents. 1946 70

Red meat intake is associated with an increased risk of developing cancer. This is possibly related to the heme content of red meat. Plant derived polyphenols might protect from cancer development via their antioxidant activities. In this study, the impact of an aqueous extract of carob (CE) on hemin-modulated proliferation was investigated. CE, gallic acid (GA) and a known iron chelator (deferoxamine: DFO) significantly reduced the number of human colon cancer HT29 cells. CE and GA were more effective under serum-free conditions than in normal cell culture medium. These effects were abolished by addition of 1 microM hemin at low concentrations of CE and GA. At higher concentrations of CE and GA, both substances reduced cell number despite hemin supplementation. Effects of CE, GA and DFO on cell number could not be linked to iron chelation even though CE and DFO were capable of chelating iron. Furthermore, the effects of high CE concentration point to antioxidative effects other than iron chelation. However, a connection to a reduction of colorectal cancer risk due to consumption of meat with high heme content by CE could not be drawn, since the effective concentrations are beyond the physiologically relevant concentrations.
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PMID:New insight into the influence of carob extract and gallic acid on hemin induced modulation of HT29 cell growth parameters. 1952 81

Different proteins regulate iron metabolism at the level of various tissues. Among these is a second transferrin receptor (TfR2) that seems to play a key role in the regulation of iron homeostasis. Although TfR2 expression in normal tissues is restricted at the level of the liver, we observed that TfR2 is frequently expressed in cancer cell lines. Taking advantage of this observation we investigated TfR2 expression in primary colon cancers, and showed that this receptor is expressed in about 26% of cases. TfR2 expression in colon cancer is not related to histological grade, but is preferentially associated with mucinous tumors. In colon cancer cell lines, TfR2 is localized in membrane lipid rafts, induces ERK1/ERK2 phosphorylation, when activated by its ligand transferring, and is preferentially expressed during S-M phases of the cell cycle. The presence of TfR2 on the membrane of colon cancer cells may contribute the growth advantage to these cells.
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PMID:TfR2 expression in human colon carcinomas. 1972 24

It is estimated that most colon cancers can be attributed to dietary causes. We have hypothesized that diet influences the health of the colonic mucosa through interaction with the microbiota and that it is the milieu interior that regulates mucosal proliferation and therefore cancer risk. To validate this further, we compared colonic contents from healthy 50- to 65-y-old people from populations with high and low risk, specifically low risk Native Africans (cancer incidence <1:100,000; n = 17), high risk African Americans (risk 65:100,000; n = 17), and Caucasian Americans (risk 50:100,000; n = 18). Americans typically consume a high-animal protein and -fat diet, whereas Africans consume a staple diet of maize meal, rich in resistant starch and low in animal products. Following overnight fasting, rapid colonic evacuation was performed with 2 L polyethylene glycol. Total colonic evacuants were analyzed for SCFA, vitamins, nitrogen, and minerals. Total SCFA and butyrate were significantly higher in Native Africans than in both American groups. Colonic folate and biotin content, measured by Lactobacillus rhamnoses and Lactobacillus plantarum ATCC 8014 bioassay, respectively, exceeded normal daily dietary intakes. Compared with Africans, calcium and iron contents were significantly higher in Caucasian Americans and zinc content was significantly higher in African Americans, but nitrogen content did not differ among the 3 groups. In conclusion, the results support our hypothesis that the microbiota mediates the effect diet has on colon cancer risk by their generation of butyrate, folate, and biotin, molecules known to play a key role in the regulation of epithelial proliferation.
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PMID:Products of the colonic microbiota mediate the effects of diet on colon cancer risk. 1974 Dec 3

Epidemiological studies have indicated that populations with high isoflavone intake through soy consumption have lower rates of breast, prostate, and colon cancer. The isoflavone polyphenol genistein in soybean is considered to be a potent chemopreventive agent against cancer. In order to explore the chemical basis of chemopreventive activity of genistein, in this paper we have examined the structure-activity relationship between genistein and its structural analogue biochanin A. We show that both genistein and its methylated derivative biochanin A are able to mobilize nuclear copper in human lymphocyte, leading to degradation of cellular DNA. However, the relative rate of DNA breakage was greater in the case of genistein. Further, the cellular DNA degradation was inhibited by copper chelator (neocuproine/bathocuproine) but not by compounds that specifically bind iron and zinc (desferrioxamine mesylate and histidine, respectively). We also compared the antioxidant activity of the two isoflavones against tert-butylhydroperoxide-induced oxidative breakage in lymphocytes. Again genistein was found to be more effective than biochanin A in providing protection against oxidative stress induced by tert-butylhydroperoxide. It would therefore appear that the structural features of isoflavones that are important for antioxidant properties are also the ones that contribute to their pro-oxidant action through a mechanism that involves redox cycling of chromatin-bound nuclear copper.
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PMID:Cellular DNA breakage by soy isoflavone genistein and its methylated structural analogue biochanin A. 1974 5

Geoditin A, an isomalabaricane triterpene isolated from the marine sponge Geodia japonica, has been demonstrated to dissipate mitochondrial membrane potential, activate caspase 3, decrease cytoplasmic proliferating cell nuclear antigen (PCNA), and induce apoptosis of leukemia cells, but the underlying mechanism remains unclear [1]. In this study, we found fragmentation of Golgi structure, suppression of transferrin receptor expression, production of oxidants, and DNA fragmentation in human colon cancer HT29 cells after treatment with geoditin A for 24 h. This apoptosis was not abrogated by chelation of intracellular iron with salicylaldehyde isonicotinoyl hydrazone (SIH), but suppressed by N-acetylcysteine (NAC), a thiol antioxidant and GSH precursor, indicating that the cytotoxic effect of geoditin A is likely mediated by a NAC-inhibitable oxidative stress. Our results provide a better understanding of the apoptotic properties and chemotherapeutical potential of this marine triterpene.
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PMID:Geoditin A induces oxidative stress and apoptosis on human colon HT29 cells. 2016 72

Although the relation between red and processed meat intake and colorectal cancer has been reported in several epidemiologic studies, very few investigated the potential mechanisms. This study examined multiple potential mechanisms in a large U.S. prospective cohort with a detailed questionnaire on meat type and meat cooking methods linked to databases for estimating intake of mutagens formed in meats cooked at high temperatures (heterocyclic amines, polycyclic aromatic hydrocarbons), heme iron, nitrate, and nitrite. During 7 years of follow-up, 2,719 colorectal cancer cases were ascertained from a cohort of 300,948 men and women. The hazard ratios (HR) and 95% confidence intervals (95% CI) comparing the fifth to the first quintile for both red (HR, 1.24; 95% CI, 1.09-1.42; P(trend) < 0.001) and processed meat (HR, 1.16; 95% CI, 1.01-1.32; P(trend) = 0.017) intakes indicated an elevated risk for colorectal cancer. The potential mechanisms for this relation include heme iron (HR, 1.13; 95% CI, 0.99-1.29; P(trend) = 0.022), nitrate from processed meats (HR, 1.16; 95% CI, 1.02-1.32; P(trend) = 0.001), and heterocyclic amine intake [HR, 1.19; 95% CI, 1.05-1.34; P(trend) < 0.001 for 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and HR, 1.17; 95% CI, 1.05-1.29; P(trend) <0.001 for 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx)]. In general, the elevated risks were higher for rectal cancer than for colon cancer, with the exception of MeIQx and DiMeIQx, which were only associated with colon cancer. In conclusion, we found a positive association for red and processed meat intake and colorectal cancer; heme iron, nitrate/nitrite, and heterocyclic amines from meat may explain these associations.
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PMID:A large prospective study of meat consumption and colorectal cancer risk: an investigation of potential mechanisms underlying this association. 2153 71

Red meat is long established as an important dietary source of protein and essential nutrients including iron, zinc and vitamin B12, yet recent reports that its consumption may increase the risk of cardiovascular disease (CVD) and colon cancer have led to a negative perception of the role of red meat in health. The aim of this paper is to review existing literature for both the risks and benefits of red meat consumption, focusing on case-control and prospective studies. Despite many studies reporting an association between red meat and the risk of CVD and colon cancer, several methodological limitations and inconsistencies were identified which may impact on the validity of their findings. Overall, there is no strong evidence to support the recent conclusion from the World Cancer Research Fund (WCRF) report that red meat has a convincing role to play in colon cancer. A substantial amount of evidence supports the role of lean red meat as a positive moderator of lipid profiles with recent studies identifying it as a dietary source of the anti-inflammatory long chain (LC) n-3 PUFAs and conjugated linoleic acid (CLA). In conclusion, moderate consumption of lean red meat as part of a balanced diet is unlikely to increase risk for CVD or colon cancer, but may positively influence nutrient intakes and fatty acid profiles, thereby impacting positively on long-term health.
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PMID:Red meat consumption: an overview of the risks and benefits. 2049 25

The abundance of cell surface levels of transferrin receptor 1 (TfR1), which regulates the uptake of iron-bound transferring, correlates with the rate of cell proliferation. Because TfR1 expression is higher in cancer cells than in normal cells, it offers a target for cancer therapy. In this study, we found that the expression of TfR1 in mouse colon cancer cells was affected by the circadian organization of the molecular clock. The core circadian oscillator is composed of an autoregulatory transcription-translation feedback loop, in which CLOCK and BMAL1 are positive regulators and the Period (Per), Cryptochrome (Cry), and Dec genes act as negative regulators. TfR1 in colon cancer-bearing mice exhibited a 24-hour rhythm in mRNA and protein levels. Luciferase reporter analysis and chromatin immunoprecipitation experiments suggested that the clock-controlled gene c-MYC rhythmically activated the transcription of the TfR1 gene. Platinum incorporation into tumor DNA and the antitumor efficacy of transferrin-conjugated liposome-delivered oxaliplatin could be enhanced by drug administration at times when TfR1 expression increased. Our findings suggest that the 24-hour rhythm of TfR1 expression may form an important aspect of strategies for TfR1-targeted cancer therapy.
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PMID:Circadian rhythm of transferrin receptor 1 gene expression controlled by c-Myc in colon cancer-bearing mice. 2063 Oct 77


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