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

Cholesterol-5 alpha, 6 alpha-epoxide has been implicated as an etiologic agent in human colon cancer. The epoxide is metabolized by human intestinal microflora to a product which was characterized by thin-layer and gas-liquid chromatography as well as combined gas-liquid chromatography-mass spectrometry. Chromatographic properties are identical with authentic cholestan-3 beta, 5 alpha, 6 beta-triol, and these results suggest that microbial epoxide hydrase activity is present in the human colon.
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PMID:Evidence of epoxide hydrase activity in human intestinal microflora. 55 96

Cholesterol and its metabolites, together with bile acids, are implicated as risk factors in the genesis and progression of colon cancer. This study was designed to determine differences in the neutral sterol composition of stools from four different population groups differing in their dietary habits as well as in their expected rates for colon cancer. Four study groups consisting of 18 Seventh-day Adventist (SDA) pure vegetarians, 50 SDA lacto-ovo vegetarians, 50 SDA nonvegetarians, and 50 general population nonvegetarians were selected from the greater Los Angeles Basin area. Three-day composite stool samples were lyophilized and then analyzed for their neutral sterol composition. Cholesterol excretion values consistently showed an age-dependent peak in 46- to 50-yr age group for the total population, SDA lacto-ovo vegetarian and SDA-nonvegetarian subgroups being the principal contributors to this age-dependent phenomenon. The SDA pure vegetarians exhibited the lowest fecal concentrations and daily excretion of cholesterol as expected since their intake of dietary cholesterol is insignificant. Among the other SDA, regardless of whether they are lacto-ovo vegetarians or nonvegetarians, their cholesterol excretion patterns were similar but higher than in the nonvegetarians from the general population. Since dietary intakes of cholesterol are not significantly different among the two nonvegetarian groups, the differences in excretion values are attributable to differences in colonic metabolism. The ratio of cholesterol/cholesterol metabolites showed generally lower values among nonvegetarians compared to the matched group of lacto-ovo vegetarians. The observation was made that fecal cholesterol and its metabolites tend to be higher among nonvegetarians compared to those in the corresponding vegetarian groups.
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PMID:Diet, nutrition intake, and metabolism in populations at high and low risk for colon cancer. Metabolism of neutral sterols. 643 44

The mechanism by which dietary cholesterol facilities colon carcinogenesis was investigated in the dimethylhydrazine-induced rat colon cancer model. Fifty female Wistar rats received a standard course of dimethylhydrazine (DMH) injections (40 mg/kg/week subcutaneously for ten weeks) while being fed Vivonex, a cholesterol-free elemental diet. Animals were allocated to one of five dietary regimens. One control group received Vivonex with added cholesterol (10 mg/100 ml Vivonex/rat/day) throughout the experiment, while another group received Vivonex alone. The remaining three groups received added cholesterol exclusively before, during or after the ten week DMH induction period. The experiment continued for over 500 days, and was evaluated by comparing, between groups, the time taken for the development of objective signs of colonic disease (time to tumour presentation or TTP). Animals either died spontaneously or were killed and autopsied. Colon cancers were confirmed histologically in every animal. The results showed that cholesterol feeding throughout the experiment or during the DMH induction period reduced the TTP compared to controls (p less than 0.05). Cholesterol prefeeding had no such effect. In the after group, the TTP was correspondingly delayed (p less than 0.05). Cholesterol-fed controls and groups receiving cholesterol during or after the DMH induction had more colon tumours and/or a greater incidence of metastases than cholesterol-free controls or those pre-fed cholesterol. The findings indicate a direct relationship between timing of cholesterol exposure and signs of colon cancer, and demonstrate that dietary cholesterol has promoter-like characteristics.
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PMID:An investigation into the mechanism of co-carcinogenesis of dietary cholesterol during the induction of colon cancer in rats by 1,2 dimethylhydrazine. 647 81

Cholesterol and fat are implicated as dietary factors enhancing the risk for colon carcinogenesis. Plant sterols such as beta-sitosterol when added to diets of experimental animals treated with colon carcinogens reduce tumor yields and counteract the proliferative changes associated with carcinogenesis. The question of whether the diet of human populations at low risk for colon cancer is mirrored in their sterol composition is addressed in this study. Four study groups consisting of 18 Seventh-day Adventist (SDA) pure vegetarians, 50 SDA lacto-ovo vegetarians, 50 SDA nonvegetarians, and 50 general population nonvegetarians were selected from the greater Los Angeles basin, and 3-day composite diets were analyzed for their sterol composition. The most significant index of dietary sterol status is the ratio, beta-sitosterol + stigmasterol/cholesterol (plant sterol/cholesterol ratio). The values for the four groups ranged from 0.49 to 16.0 (general population nonvegetarians = 0.49; SDA-nonvegetarians = 0.98; SDA lacto-ovo vegetarians = 3.26; SDA pure vegetarians = 16.0). The data also show that the absolute amounts of cholesterol consumed as a factor by itself might not be as significant as its relationship to total plant sterols in the diet.
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PMID:Diet, nutrition intake, and metabolism in populations at high and low risk for colon cancer. Dietary cholesterol, beta-sitosterol, and stigmasterol. 648 1

Cholesterol feeding of rats with colon cancer induced by dimethylhydrazine results in reduced survival and an increased incidence of metastatic colon cancer. As cholesterol may be implicated in the induction or maintenance of the metastatic process, an experiment was designed to determine whether rats with colon cancer would benefit from the removal of cholesterol from the diet. Female Wistar rats were treated with a colon cancer-inducing regimen of dimethylhydrazine (40 mg/kg/week for 10 weeks) while being fed on a standard cholesterol-containing rat pellet diet. After two rats had died spontaneously of histologically proven adenocarcinoma of the colon at 24 weeks, the remaining rats were randomly allocated in groups of 15 to one of three dietary regimens. Group S continued to receive standard pellet diet, group V were fed on Vivonex alone and group VC were fed Vivonex plus cholesterol (10 mg/100 ml Vivonex). Each group was assessed for survival and incidence of histologically proven metastatic disease. There were no differences in either survival or incidence of metastases when groups S and VC were compared. In the cholesterol deprived group V, however, there was a significant increase in survival compared with groups S and VC (p less than 0.02) and this was due to a significant reduction in the incidence of metastases (p less than 0.05). Cholesterol deprivation therefore benefits rats with established colon cancer induced by dimethylhydrazine by improving survival and reducing the incidence of metastases.
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PMID:Dietary cholesterol deprivation improves survival and reduces incidence of metastatic colon cancer in dimethylhydrazine-pretreated rats. 708 5

Average daily intakes of several components of fat in the diets of the five main ethnic groups in Hawaii were determined from personal interviews of 4137 subjects regarding their food consumption in a usual week. In general, fat intake was highest among Caucasians and lowest among Filipinos. Cholesterol intake did not follow the same pattern as that of the other fat components. The intake of total fat showed good correlation with the ethnic-specific incidence rates of breast cancer in Hawaii but not with colon or prostate cancer rates. There was no correlation of cholesterol intake with colon cancer incidence.
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PMID:Dietary fat intake and cancer incidence among five ethnic groups in Hawaii. 726 Sep 32

Tumors derived from the colonic epithelium exhibit cholesterol metabolism which is clearly different from that in fibroblasts, hepatocytes, adrenals, and ovaries. In hepatocytes and fibroblasts MEV inhibition of the rate limiting step in cholesterol synthesis HMG Co A reductase can be overcome by the uptake of LDL. Colon cancer cells however do not overcome MEV inhibition by LDL uptake but rather exhibit further growth suppression Mevinolin (Mevacor), a drug used to lower serum cholesterol levels has the advantage of accumulating in the liver to approximately 95% with the first pass. A small but variable percentage of non-sterol precursors may escape inhibition and be utilized for other pathways in the isoprenylation of certain proteins, among them members of the ras family. Mutated ras, an oncogene, is found in 40-50% of colon tumors and the expression of a functional gene product is dependent on isoprenylation for anchorage to the tumor cell membrane. d-Limonene, a relatively non-toxic monoterpene found in orange skin oil, selectively inhibits isoprenylation and also accumulates to some extent in the liver. It was hypothesized that the differences in mevalonate metabolism between hepatocytes and colon tumor cells could provide a chemotherapeutic advantage in which MEV and/or d-limonene could effectively inhibit cholesterol synthesis and post-translational modification of proteins with non-sterol cholesterol precursors in colon tumor derived hepatic metastases and thus inhibit their growth. Since each drug affects aspects of mevalonate synthesis at different points, the effects of the combination of their agents on inhibiting tumor metastases was investigated to ascertain if these could be additive. In tissue culture, MEV and d-limonene significantly inhibited the growth of CT-26, a murine transplantable colon tumor. Cholesterol synthesis assessed in these cells indicated that in lipid deficient media the following additions-25-hydroxycholesterol, and LDL significantly reduced cholesterol synthesis. Conversely, perillyl alcohol increased cholesterol synthesis 2.5 fold. In cells cultured in FBS based medium, which have an FBS control, MEV treatment reduced cholesterol synthesis to 65% of control. Perillyl alcohol increased synthesis 1.4 fold and when given in conjunction with MEV, it abolished the effects of this inhibitor. In isoprenylation studies of 14C-mevalonate incorporation into proteins, MEV impaired isoprenylation by restricting synthesis of mevalonate derived intermediates. Results of CT-26 treatment with perillyl alcohol are inconsistent with its putative role as a protein isoprenylation inhibitor. The combination of these agents indicates an additive action which requires additional investigation to elucidate their mechanism(s). Dietary MEV and d-limonene were evaluated alone and in combination for their chemotherapeutic potential in a hepatic "metastasis" model. Using splenic colonization in which CT-26 was implanted into the spleen and ultimately seeded the liver, each of these compounds were found to inhibit the growth of resultant tumors both alone and in combination by approximately 80% versus controls at 35 days post-implantation. Assessment of HMGCoA reductase in liver and tumor indicated that these agents were effective in reaching these target sites. The findings to date indicate that while d-limonene and MEV may differentially affect the same pathway, and their individual actions may appear antagonistic in vitro, their overall action individually or together, appears promising as a chemotherapeutic modality for the possible management of hepatic metastases from colon cancer.
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PMID:Effects of monoterpenes and mevinolin on murine colon tumor CT-26 in vitro and its hepatic "metastases" in vivo. 888 30

The purpose of the present study was to examine the effect of beta-sitosterol, the main dietary phytosterol on the growth of HT-29 cells, a human colon cancer cell line. In addition, the incorporation of this phytosterol into cellular membranes and how this might influence the lipid composition of the membranes were investigated. Tumor cells were grown in DMEM containing 10% FBS and supplemented with sterols (cholesterol or beta-sitosterol) at final concentrations up to 16 microM. The sterols were supplied to the media in the form of sterol cyclodextrin complexes. The cyclodextrin used was 2-hydroxypropyl-beta-cyclodextrin. The sterol to cyclodextrin molar ratio was maintained at 1:300. The study indicated that 8 and 16 microM beta-sitosterol were effective at cel growth inhibition as compared to cholesterol or to the control (no sterol supplementation). After supplementation with 16 microM beta-sitosterol for 9 days, cell growth was only one-third that of cells supplemented with equimolar concentration of cholesterol. No effect was observed on total membrane phospholipid concentration. At 16 microM beta-sitosterol supplementation, membrane cholesterol was reduced by 26%. Cholesterol supplementation resulted in a significant increase in the cholesterol/phospholipid ratio compared to either beta-sitosterol supplemented cells or controls. There was a 50% reduction in membrane sphingomyelin (SM) of cells grown in 16 microM beta-sitosterol. Additional changes were observed in the fatty acid composition of minor phospholipids of beta-sitosterol supplemented cells, such as SM, phosphatidylserine (PS), and phosphatidylinositol (PI). Only in the case of PI, was there an effect of these fatty acid changes on the unsaturation index, beta-sitosterol incorporation resulted in an increase in the U.I. It is possible that the observed growth inhibition by beta-sitosterol may be mediated through the influence of signal transduction pathways that involve membrane phospholipids.
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PMID:beta-Sitosterol inhibits HT-29 human colon cancer cell growth and alters membrane lipids. 891 88

Epidemiological studies have shown a positive association of colon cancer with hyperlipidemia. Furthermore, signaling generated by peroxisome proliferator-activated receptor (PPAR) alpha and gamma ligands, suggested to be candidate tumor preventive agents, has been shown to lower serum triglyceride levels. In the present study, we assessed hyperlipidemia in Apc-deficient mice, model animals for human familial adenomatous polyposis, and examined the effects of pioglitazone and bezafibrate, respectively, PPARgamma and PPARalpha agonists, on both hyperlipidemia and intestinal polyposis. Serum lipid levels in Apc(1309) mice and Min mice from 6 to 15 weeks of age were measured. Although serum levels of triglyceride and cholesterol were low in both Apc(1309) and wild-type mice at 6 weeks, triglycerides were elevated 10-fold in Apc(1309) mice by the age of 12 weeks but not in their wild-type counterparts. Cholesterol was also increased significantly, and marked centrilobular-restricted steatosis was observed in the livers of aged Apc(1309) mice. Similar findings were observed for Min mice at 15 weeks of age. Moreover, lipoprotein lipase mRNA levels in the liver and small intestine of Apc(1309) and Min mice were demonstrated to be lower than those in wild-type mice. Treatment of Apc(1309) mice with 100 and 200 ppm pioglitazone or bezafibrate for 6 weeks from 6 weeks of age caused dose-dependent reduction in serum triglycerides and cholesterol, along with reduction in the numbers of intestinal polyps to 67% of the control value. The present study clearly demonstrated a hyperlipidemic state in Apc gene-deficient mice and a potential of PPARalpha and PPARgamma ligands to suppress both hyperlipidemia and polyp formation. Hyperlipidemia in these mice may thus be associated with their intestinal lesion development.
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PMID:Concomitant suppression of hyperlipidemia and intestinal polyp formation in Apc-deficient mice by peroxisome proliferator-activated receptor ligands. 1452 40

Bile acids have long been implicated in the etiology of colorectal cancer, but epidemiologic evidence remains elusive. Cholesterol 7alpha-hydroxylase (CYP7A1) is the rate-limiting enzyme in the synthesis of bile acids from cholesterol in the liver, and thus may be an important determinant of bile acid production. We examined the association between the CYP7A1 A-203C polymorphism and colorectal cancer. The CYP7A1 A-203C polymorphism was determined by the PCR-RFLP method in 685 incident cases of colorectal cancer and 778 controls randomly selected from a community in the Fukuoka area, Japan. The CC genotype was slightly less frequent in the case group, and the adjusted odds ratio for the CC versus AA genotype was 0.88 (95% confidence interval, 0.65-1.20). In the analysis by subsite of the colorectum, a decreased risk associated with the CYP7A1 CC genotype was observed for proximal colon cancer, but not for either distal colon or rectal cancer. The adjusted odds ratios (95% confidence intervals) of proximal colon cancer for the CC genotype were 0.63 (0.36-1.10) compared with the AA genotype, and 0.59 (0.37-0.96) compared with the AA and AC genotypes combined. A decreased risk of proximal colon cancer in relation to the CC genotype of CYP7A1 A-203C, which probably renders less activity of the enzyme converting cholesterol to bile acids, is new evidence for the role of bile acids in colorectal carcinogenesis.
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PMID:Genetic polymorphism in cytochrome P450 7A1 and risk of colorectal cancer: the Fukuoka Colorectal Cancer Study. 1580 2


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