pectins and Adenocarcinoma

Because anticarcinogenic and tumor-growth-inhibiting effects of nonsoluble fibers have been described, similar actions of soluble fibers appear to merit investigation. In a preliminary study on methylnitrosourea-induced mammary carcinogenesis in Sprague-Dawley female rats, 15% oligofructose added to the basal diet modulated this carcinogenesis in a negative manner. There was a lower number of tumor-bearing rats and a lower total number of mammary tumors in oligofructose-fed rats than in the group fed the basal diet alone. The effect of dietary nondigestible carbohydrates (15% oligofructose, inulin or pectin incorporated into the basal diet) on the growth of intramuscularly transplanted mouse tumors, belonging to two tumor lines (TLT and EMT6), was also investigated. The results were evaluated by regular tumor measurements with a vernier caliper. The mean tumor surface in the experimental groups was compared with that in animals of the control group fed the basal diet containing starch as the only carbohydrate. The growth of both tumor lines was significantly inhibited by supplementing the diet with nondigestible carbohydrates. Such nontoxic dietary treatment appears to be easy and risk free for patients, applicable as an adjuvant factor in the classical protocols of human cancer therapy.

Topics: Adenocarcinoma; Animals; Carcinogens; Dietary Carbohydrates; Female; Humans; Inulin; Mammary Neoplasms, Animal; Methylnitrosourea; Mice; Neoplasm Transplantation; Oligosaccharides; Pectins; Rats; Rats, Sprague-Dawley

Tumor-associated macrophages (TAMs) have been shown to be associated with poor prognosis of cancer and are predominately localized in the hypoxia regions of tumor. We demonstrated in this study that hypoxia increases the synthesis and secretion of galectin-3 by TAMs. The increased expression of galectin-3 in TAMs was seen to be associated with nucleation of transcription factor NF-κB through generation and activation of ROS and promoted tumor growth and metastasis in vitro and in mice through multiple molecular mechanisms. It was found that the TAMs-mediated promotion of tumor growth and metastasis in hypoxia was inhibited by administration of macrophage-depletion agent clodronate liposomal (CL) or galectin-3 inhibitor modified citric pectin (MCP) in orthotopic syngeneic mammary adenocarcinoma model and metastasis model. Co-administration of anti-angiogenesis agent sorafenib or bevacizumab with CL and MCP showed to cause stronger inhibition of tumor growth and metastasis than administration of each agent alone. These results indicate that hypoxia-induced galectin-3 expression and secretion from TAMs promotes tumor growth and metastasis. Targeting the actions of galectin-3 in hypoxia may be a potential therapeutic strategy for cancer treatment.

Topics: Adenocarcinoma; Animals; Bevacizumab; Breast Neoplasms; Cell Line, Tumor; Cell Movement; Cell Proliferation; Clodronic Acid; Coculture Techniques; Disease Progression; Female; Galectin 3; Gene Expression Regulation, Neoplastic; Humans; Hypoxia; Lymphatic Metastasis; Macrophages; Mammary Neoplasms, Experimental; Mice; Mice, Inbred BALB C; Mice, Nude; Neovascularization, Pathologic; NF-kappa B; Pectins; Signal Transduction; Sorafenib

The objective of this study was to investigate the in vitro cytotoxicity and in vivo anticancer efficacy of redox-responsive microbeads containing thiolated pectin-doxorubicin (DOX) conjugate. Oral microbeads were coated with an enteric polymer to protect the drug from release in the upper gastrointestinal (GI) tract and allow redox-triggered drug release in the colon. Morphology, particle size, drug content, and in vitro drug release behavior of the microbeads were characterized; in vitro cytotoxicity was tested on mouse colon carcinoma, human colorectal adenocarcinoma, and human bone osteosarcoma cell lines. In vivo anticancer efficacy of coated microbeads was examined in BALB/c mice with murine colon carcinoma. These coated microbeads significantly inhibited the growth of all cell lines. The in vivo study confirmed delivery of DOX to the colorectal tumor site, redox-responsiveness, and anticancer efficacy of coated microbeads. Coated microbeads also effectively inhibited primary tumor growth and suppressed tumor metastases without gross toxicity to the non-target tissue. No noticeable damage was found in mouse GI tissues, indicating lack of DOX toxicity. These novel coated microbeads containing thiolated pectin-DOX conjugate may be a promising vehicle for targeted clinical delivery of DOX to the colorectal cancer site by oral administration.

Topics: Adenocarcinoma; Animals; Antibiotics, Antineoplastic; Bone Neoplasms; Caco-2 Cells; Cell Proliferation; Colorectal Neoplasms; Delayed-Action Preparations; Doxorubicin; Drug Carriers; Drug Compounding; Drug Liberation; HT29 Cells; Humans; Male; Mice, Inbred BALB C; Osteosarcoma; Oxidation-Reduction; Pectins; Sulfhydryl Compounds; Technology, Pharmaceutical; Time Factors; Tumor Burden

Pectin and its several modified forms have shown remarkable impact in therapeutic use against various cancers. In the present study, pectin, an anionic polysaccharide isolated from Musa paradisiaca is employed for the synthesis of gold nanoparticles at ambient temperature conditions. The synthesized nanoparticles were characterized using microscopic and spectroscopic studies and its anti-cancer potential was evaluated in mammary adenocarcinoma cell lines MCF-7 and MDA-MB-231. Apoptosis induction was evident from increase in sub-G1 population studied using flow cytometry analysis. DNA damage followed by cell death in pectin mediated gold nanoparticles (p-GNPs) treated cells was confirmed by Comet assay. Uptake of p-GNPs by cancer cells (MCF-7 and MDA-MB-231) was analyzed using FE-SEM which revealed the presence of p-GNPs as aggregates over the surface of cells with loss in cellular integrity compared to control cells.

Topics: Adenocarcinoma; Antineoplastic Agents; Apoptosis; Breast Neoplasms; Cell Survival; Drug Screening Assays, Antitumor; Female; Gold; Humans; MCF-7 Cells; Metal Nanoparticles; Particle Size; Pectins; Surface Properties

Polysaccharide containing extracts from immature fruits of okra (Abelmoschus esculentus) are known to exhibit antiadhesive effects against bacterial adhesion of Helicobacter pylori (H. pylori) to stomach tissue. The present study investigates structural and functional features of polymers responsible for this inhibition of bacterial attachment to host cells. Ammonium sulfate precipitation of an aqueous extract yielded two fractions at 60% and 90% saturation with significant antiadhesive effects against H. pylori, strain J99, (FE60% 68% ± 15%; FE90% 75% ± 11% inhibition rates) after preincubation of the bacteria at 1 mg/mL. Sequential extraction of okra fruits yielded hot buffer soluble solids (HBSS) with dose dependent antiadhesive effects against strain J99 and three clinical isolates. Preincubation of H. pylori with HBSS (1 mg/mL) led to reduced binding to 3'-sialyl lactose, sialylated Le(a) and Le(x). A reduction of bacterial binding to ligands complementary to BabA and SabA was observed when bacteria were pretreated with FE90%. Structural analysis of the antiadhesive polysaccharides (molecular weight, monomer composition, linkage analysis, stereochemistry, and acetylation) indicated the presence of acetylated rhamnogalacturonan-I polymers, decorated with short galactose side chains. Deacetylation of HBSS and FE90% resulted in loss of the antiadhesive activity, indicating esterification being a prerequisite for antiadhesive activity.

Topics: Abelmoschus; Acetylation; Adenocarcinoma; Bacterial Adhesion; Bacterial Outer Membrane Proteins; Fruit; Helicobacter Infections; Helicobacter pylori; Humans; Pectins; Plant Extracts; Polysaccharides; Stomach Neoplasms; Tumor Cells, Cultured

Calcium, phytic acid, polyphenols and fiber are major inhibitors of iron absorption and they could be found in excess in some diets, thereby altering or modifying the iron nutrition status. The purpose of this study is to evaluate the effect of calcium, tannic acid, phytic acid, and pectin over iron uptake, using an in vitro model of epithelial cells (Caco-2 cell line). Caco-2 cells were incubated with iron (10-30 μM) with or without CaCl2 (500 and 1,000 μM) for 24 h. Then, cells were challenged with phytic acid (50-150 μM); pectin (50-150 nM) or tannic acid (100-500 μM) for another 24 h. Finally, (55)Fe (10 μM) uptake was determined. Iron dialyzability was studied using an in vitro digestion method. Iron uptake in cells pre-incubated with 20 and 30 μM Fe was inhibited by CaCl2 (500 μM). Iron uptake decreased in cells cultured with tannic acid (300 μM) and CaCl2 (500-1,000 μM) (two-way ANOVA, p = 0.002). Phytic acid also decreased iron uptake mainly when cells were treated with CaCl2 (1,000 μM) (two-way ANOVA; p < 0.05). Pectin slightly decreased iron uptake (p = NS). Iron dialyzability decreased when iron was mixed with CaCl2 and phytic or tannic acid (T test p < 0.0001, for both) but not when mixed with pectin. Phytic acid combined with calcium is a strong iron uptake inhibitor. Pectin slightly decreased iron uptake with or without calcium. Tannic acid showed an unexpected behavior, inducing an increase on iron uptake, despite its low Fe dialyzability.

Topics: Adenocarcinoma; Analysis of Variance; Caco-2 Cells; Calcium; Calcium Chloride; Colonic Neoplasms; Dose-Response Relationship, Drug; Humans; Intestinal Absorption; Iron; Models, Biological; Pectins; Phytic Acid; Tannins

In Malian traditional medicine infusions of the roots of Vernonia kotschyana or Cochlospermum tinctorium in water are used for treating gastric ulcer. Helicobacter pylori is known to play a major role in gastric ulcer development, and it was of interest to evaluate a potential anti-adhesive activity towards H. pylori by crude water extracts and isolated polysaccharide fractions from the roots of V. kotschyana and C. tinctorium. The inhibitory effects were examined by an in vitro flow cytometric assay using human gastric adenocarcinoma epithelial cells, where fluorescent-labeled H. pylori were pre-treated with the test fractions. The crude extract Ctw50 from C. tinctorium, containing a mixture of inulin, pectic polysaccharides, phenols and protein, led to a 43% reduction of bacterial attachment. The isolated pectic type fractions CtwA1 and CtwA2 from C. tinctorium, and Vko-I from V. kotschyana resulted in approximately 30% inhibition of H. pylori adhesion. These fractions consist of rhamnogalacturonan backbones with side chains of arabinogalactans and/or arabinans. The low degree of uronic acids in the fractions compared to anti-adhesive polysaccharides reported previously, suggests that the neutral side chains might play a role in the binding of bacterial adhesins. The fraction Vko-III.1 from V. kotschyana consisting mainly of galacturonic acid resulted only in a 19% inhibition of H. pylori adhesion. The anti-adhesive properties shown by the crude water extracts and isolated polysaccharide fractions in the present study might partly explain the anti-ulcer activities by the roots of V. kotschyana and C. tinctorium.

Topics: Adenocarcinoma; Bixaceae; Cell Adhesion; Epithelial Cells; Galactans; Helicobacter pylori; Humans; Medicine, Traditional; Pectins; Phenols; Plant Extracts; Plant Roots; Polysaccharides; Stomach Ulcer; Vernonia

In situ coating of 5-fluorouracil pellets by ethylcellulose and pectin powder mixture (8:3 weight ratio) in capsule at simulated gastrointestinal media provides colon-specific drug release in vitro. This study probes into pharmacodynamic and pharmacokinetic profiles of intra-capsular pellets coated in vivo in rats with reference to their site-specific drug release outcomes. The pellets were prepared by extrusion-spheronization technique. In vitro drug content, drug release, in vivo pharmacokinetics, local colonic drug content, tumor, aberrant crypt foci, systemic hematology and clinical chemistry profiles of coated and uncoated pellets were examined against unprocessed drug. In vivo pellet coating led to reduced drug bioavailability and enhanced drug accumulation at colon (179.13 μg 5-FU/g rat colon content vs 4.66 μg/g of conventional in vitro film-coated pellets at 15 mg/kg dose). The in vivo coated pellets reduced tumor number and size, through reforming tubular epithelium with basement membrane and restricting expression of cancer from adenoma to adenocarcinoma. Unlike uncoated pellets and unprocessed drug, the coated pellets eliminated aberrant crypt foci which represented a putative preneoplastic lesion in colon cancer. They did not inflict additional systemic toxicity. In vivo pellet coating to orally target 5-fluorouracil delivery at cancerous colon is a feasible therapeutic treatment approach.

Topics: Aberrant Crypt Foci; Adenocarcinoma; Adenoma; Administration, Oral; Animals; Antimetabolites, Antineoplastic; Biological Availability; Cellulose; Chemistry, Pharmaceutical; Colonic Neoplasms; Dimethylhydrazines; Drug Delivery Systems; Feasibility Studies; Female; Fluorouracil; Pectins; Powders; Rats, Sprague-Dawley; Solubility; Tablets, Enteric-Coated; Technology, Pharmaceutical; Tumor Burden

We have hypothesized that dietary modulation of intestinal non-coding RNA [microRNA (miRNA)] expression may contribute to the chemoprotective effects of nutritional bioactives (fish oil and pectin). To fully understand the effects of these agents on the expression of miRNAs, Sprague-Dawley rats were fed diets containing corn oil or fish oil with pectin or cellulose and injected with azoxymethane (AOM, a colon-specific carcinogen) or saline (control). Real-time polymerase chain reaction using miRNA-specific primers and Taq Man probes was carried out to quantify effects on miRNA expression in colonic mucosa. From 368 mature miRNAs assayed, at an early stage of cancer progression (10 week post AOM injection), let-7d, miR-15b, miR-107, miR-191 and miR-324-5p were significantly (P < 0.05) affected by diet x carcinogen interactions. Overall, fish oil fed animals exhibited the smallest number of differentially expressed miRNAs (AOM versus saline treatment). With respect to the tumor stage (34 week post AOM injection), 46 miRNAs were dysregulated in adenocarcinomas compared with normal mucosa from saline-injected animals. Of the 27 miRNAs expressed at higher (P < 0.05) levels in tumors, miR-34a, 132, 223 and 224 were overexpressed at >10-fold. In contrast, the expression levels of miR-192, 194, 215 and 375 were dramatically reduced (< or = 0.32-fold) in adenocarcinomas. These results demonstrate for the first time the utility of the rat AOM model and the novel role of fish oil in protecting the colon from carcinogen-induced miRNA dysregulation.

Topics: Adenocarcinoma; Animals; Azoxymethane; Carcinogens; Colon; Colonic Neoplasms; Epigenesis, Genetic; Fatty Acids, Unsaturated; Fish Oils; Gene Expression Profiling; Male; MicroRNAs; Pectins; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction

The role of dietary components in cancer progression and metastasis is an emerging field of clinical importance. Many stages of cancer progression involve carbohydrate-mediated recognition processes. We therefore studied the effects of high pH- and temperature-modified citrus pectin (MCP), a nondigestible, water-soluble polysaccharide fiber derived from citrus fruit that specifically inhibits the carbohydrate-binding protein galectin-3, on tumor growth and metastasis in vivo and on galectin-3-mediated functions in vitro.. In vivo tumor growth, angiogenesis, and metastasis were studied in athymic mice that had been fed with MCP in their drinking water and then injected orthotopically with human breast carcinoma cells (MDA-MB-435) into the mammary fat pad region or with human colon carcinoma cells (LSLiM6) into the cecum. Galectin-3-mediated functions during tumor angiogenesis in vitro were studied by assessing the effect of MCP on capillary tube formation by human umbilical vein endothelial cells (HUVECs) in Matrigel. The effects of MCP on galectin-3-induced HUVEC chemotaxis and on HUVEC binding to MDA-MB-435 cells in vitro were studied using Boyden chamber and labeling assays, respectively. The data were analyzed by two-sided Student's t test or Fisher's protected least-significant-difference test.. Tumor growth, angiogenesis, and spontaneous metastasis in vivo were statistically significantly reduced in mice fed MCP. In vitro, MCP inhibited HUVEC morphogenesis (capillary tube formation) in a dose-dependent manner. In vitro, MCP inhibited the binding of galectin-3 to HUVECs: At concentrations of 0.1% and 0.25%, MCP inhibited the binding of galectin-3 (10 micro g/mL) to HUVECs by 72.1% (P =.038) and 95.8% (P =.025), respectively, and at a concentration of 0.25% it inhibited the binding of galectin-3 (1 micro g/mL) to HUVECs by 100% (P =.032). MCP blocked chemotaxis of HUVECs toward galectin-3 in a dose-dependent manner, reducing it by 68% at 0.005% (P<.001) and inhibiting it completely at 0.1% (P<.001). Finally, MCP also inhibited adhesion of MDA-MB-435 cells, which express galectin-3, to HUVECs in a dose-dependent manner.. MCP, given orally, inhibits carbohydrate-mediated tumor growth, angiogenesis, and metastasis in vivo, presumably via its effects on galectin-3 function. These data stress the importance of dietary carbohydrate compounds as agents for the prevention and/or treatment of cancer.

Topics: Adenocarcinoma; Administration, Oral; Animals; Antineoplastic Agents, Phytogenic; Blotting, Western; Breast Neoplasms; Chemotaxis; Citrus; Colonic Neoplasms; Disease Progression; Dose-Response Relationship, Drug; Endothelium, Vascular; Fluorescent Antibody Technique, Indirect; Galectin 3; Immunohistochemistry; Mice; Mice, Nude; Neoplasm Metastasis; Neoplasm Transplantation; Neoplasms; Neovascularization, Pathologic; Pectins; Recombinant Proteins; Tumor Cells, Cultured; Umbilical Veins

Because of the potential significance of colonic bacteria in colon carcinogenesis, we investigated the effect of pectin of different types on fecal bacterial enzymes (beta-glucuronidase, beta-glucosidase and tryptophanase) at various periods of time after feeding rats with pectin-containing diets during azoxymethane-induced colon carcinogenesis. The diet supplemented with 20% apple pectin or 20% citrus pectin decreased the multiplicity of colon tumors, and the number of tumors was significantly decreased in the group fed apple pectin. The incidence of colon tumors in the apple pectin group was lower than that in the control group. The mean tumor size was similar among the three groups. Apple pectin feeding decreased fecal beta-glucosidase and tryptophanase levels. Furthermore, a significant decrease in the activity of beta-glucuronidase was observed in the apple pectin group during the initiation phase. These findings suggest that the protective effect of pectin on colon carcinogenesis may be dependent on the type of pectin and be related to the decrease of beta-glucuronidase activity in the initiation stage of carcinogenesis.

Topics: Adenocarcinoma; Animals; Azoxymethane; beta-Glucosidase; Body Weight; Carcinoma, Signet Ring Cell; Colonic Neoplasms; Feces; Fruit; Glucuronidase; Male; Pectins; Rats; Tryptophanase

Prostate cancer is the most common cancer diagnosed in U.S. men and remains incurable once it has metastasized. Many stages of the metastatic cascade involve cellular interactions mediated by cell surface components, such as carbohydrate-binding proteins, including galactoside-binding lectins (galectins). Modified citrus pectin (pH-modified), a soluble component of plant fiber derived from citrus fruit, has been shown to interfere with cell-cell interactions mediated by cell surface carbohydrate-binding galectin-3 molecules.. The aim of this study was to determine whether modified citrus pectin, a complex polysaccharide rich in galactosyl residues, could inhibit spontaneous metastasis of prostate adenocarcinoma cells in the rat.. The ability of modified citrus pectin to inhibit the adhesion of Dunning rat prostate cancer MAT-LyLu cells to rat endothelial cells was measured by 51Cr-labeling. Modified citrus pectin inhibition of MAT-LyLu cell anchorage-independent growth was measured by colony formation in agarose. The presence of galectin-3 in rat MAT-LyLu cells and human prostate carcinoma was demonstrated by immunoblotting and immunohistochemistry. One million MAT-LyLu cells were injected subcutaneously into the hind limb of male Copenhagen rats on day 0. Rats were given 0.0%, 0.01%, 0.1%, or 1.0% (wt/vol) modified citrus pectin continuously in their drinking water (from day 4 until necropsy on day 30). The number of MAT-LyLu tumor colonies in the lungs were counted.. Compared with 15 or 16 control rats that had lung metastases on day 30, seven of 14 rats in the 0.1% and nine of 16 rats in the 1.0% modified citrus-pectin group had statistically significant (two-sided; P < .03 and P < .001, respectively) reductions in lung metastases. The lungs of the 1.0% modified citrus pectin-treated rats had significantly (two-sided; P < .05) fewer metastatic colonies than control groups (9 colonies +/- 4 [mean +/- SE] in the control group compared with 1 colony +/- 1 in the treated group). Modified citrus pectin had no effect on the growth of the primary tumors. In vitro, modified citrus pectin inhibited MAT-LyLu cell adhesion to rat endothelial cells in a time- and dose-dependent manner as well as their colony formation in semisolid medium.. We present a novel therapy in which oral intake of modified citrus pectin acts as a potent inhibitor of spontaneous prostate carcinoma metastasis in the Copenhagen rat.. Further investigations are warranted to determine the following: 1) the role of galectin-3 in normal and cancerous prostate tissues and 2) the ability of modified citrus pectin to inhibit human prostate metastasis in nude mice.

Topics: Adenocarcinoma; Administration, Oral; Analysis of Variance; Animals; Cell Adhesion; Cell Separation; Disease Models, Animal; Electrophoresis, Polyacrylamide Gel; Fluorescent Antibody Technique; Humans; Immunoblotting; Immunoenzyme Techniques; Male; Neoplasm Metastasis; Pectins; Prostatic Neoplasms; Rats; Tumor Stem Cell Assay

The effect of dietary supplementation with pectin and/or guar gum on 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis was studied using 120 male Sprague-Dawley rats. The rats were given a weekly injection of DMH for 8 weeks and were maintained on a basal fiber-free diet supplemented with 5% cellulose. The rats were then subdivided into four groups and kept on the basal fiber-free diet supplemented with either no fiber, 10% pectin, 10% guar gum or a combination of 5% pectin/5% guar gum for a period of 24 weeks. The 8 weeks of DMH administration were defined as the initiation stage of carcinogenesis and the next 24 weeks were defined as the promotional stage of carcinogenesis. Food and water were available ad libitum. The rats were killed 32 weeks after the start of the experiment and tumor incidence, location and frequency in the colon were determined. Other parameters measured were body weight and caloric intake. Dietary fiber supplementation with 10% pectin or with 10% guar gum but not with the combination of 5% pectin/5% guar gum (fed during the promotional stage of carcinogenesis), was found to suppress colon cancer incidence to a significant extent.

Topics: 1,2-Dimethylhydrazine; Adenocarcinoma; Animals; Carcinogens; Colonic Neoplasms; Dietary Fiber; Dimethylhydrazines; Energy Intake; Galactans; Male; Mannans; Pectins; Plant Gums; Rats; Rats, Inbred Strains

Seven-week-old Sprague-Dawley rats were fed a semipurified AIN76 diet and were given a weekly injection of the colon carcinogen 1,2-dimethylhydrazine for 8 weeks (initiation stage of carcinogenesis). The rats were divided into seven groups and each group of rats was placed on one of seven different modifications of the AIN76 diet for the next 24 weeks (promotional stage of carcinogenesis). The mean numbers of aberrant crypt foci/rat and the incidence of adenocarcinomas from some of the seven dietary groups were found to be significantly different. However, all attempts to show a significant correlation between the mean number of aberrant crypt foci/rat and the incidence of adenocarcinomas failed. Therefore, the number of aberrant crypt foci/rat cannot by itself be used as a reliable quantitative predictor (biomarker) of the efficacy of dietary intervention or of chemopreventive procedures on modulating the risk of developing colon cancer. This conclusion emphasizes the need for end point validation of potential cancer biomarkers before the biomarkers can be considered predictive of modulation of the risk for colon cancer.

Topics: Adenocarcinoma; Analysis of Variance; Animals; Colon; Colonic Neoplasms; Corn Oil; Diet; Dimethylhydrazines; Male; Pectins; Prognosis; Rats; Rats, Inbred Strains; Regression Analysis

The comparative effects of different fibers on colonic luminal pH, crypt cell proliferation, and colon carcinogenesis were studied in 120 male Sprague-Dawley rats. The animals were divided into five equal groups and fed either a basal fiber free diet or the basal diet supplemented with 10% pectin, cellulose or guar, or 20% oat bran for up to 30 weeks. 1,2-Dimethylhydrazine was given at 20 mg/kg body weight as a weekly s.c. injection for 12 weeks. Food intake and weight gain were similar in all diet groups. At sacrifice, in vivo pH measurements showed that compared to fiber free rats, all fibers significantly acidified large bowel luminal contents (P less than 0.05). In the guar group 62.5% of rats developed colonic tumors compared to 33.4% of the fiber free rats (P less than 0.05). The yield of proximal colonic adenocarcinomas in the oat bran, pectin, and guar groups was increased by 4.5 to 5 times over the fiber free level (P less than 0.05-0.025). Pectin and guar provided the greatest stimulus to cell proliferation. A lower luminal pH was associated with a higher tumor yield and increased epithelial cell proliferation. Thus, acidification of colonic contents by high fiber diets failed to inhibit rat colon carcinogenesis, while the consumption of soluble fibers, such as oat bran, pectin, and guar, was associated with enhancement of proximal colon carcinogenesis.

Topics: 1,2-Dimethylhydrazine; Adenocarcinoma; Animals; Cell Division; Cellulose; Colon; Colonic Neoplasms; Dietary Fiber; Dimethylhydrazines; Feces; Galactans; Hydrogen-Ion Concentration; Male; Mannans; Pectins; Plant Gums; Rats; Rats, Inbred Strains

The effect of 5% low-methoxylated pectin, high-methoxylated pectin, and guar gum on 1,2-dimethylhydrazine initiation of colon cancer was investigated using groups of 30 rats. The growth of the rats in the different groups was very similar to that of control group fed a fiber-free diet. Both kinds of pectin increased the multiplicity of color tumors, whereas guar gum did not significantly influence carcinogenesis. Bacterial beta-glucuronidase activity in feces and colonic content was the same in pectin-fed rats and controls but significantly lower in the guar gum group. Thus, it was not related to the number of tumors in each group.

Topics: Adenocarcinoma; Animals; Bacteria; Body Weight; Cellulose; Colonic Neoplasms; Dietary Fiber; Dimethylhydrazines; Feces; Glucuronidase; Male; Methylhydrazines; Pectins; Rats

The incidence, distribution, size, and histopathology of colonic tumors induced by parenteral administration of 1,2-dimethylhydrazine were examined in rats fed a chemically defined fiber-free diet or nutritionally and calorically equivalent diets containing either 4.5 or 9.0% purified cellulose or pectin. This double-blind study indicates that cellulose is protective against experimental colonic neoplasia. Although the precise mechanism for this protective effect remains to be elucidated, it was not cellulose dose dependent and appeared to depend on administration during injection of carcinogen. Furthermore, this study provides strong evidence that identical amounts of cellulose and pectin fed as the sole source of fiber in chemically defined diets exert strikingly different effects in relation to development of intestinal neoplasia in this animal model.

Topics: Adenocarcinoma; Animals; Cellulose; Colonic Neoplasms; Dietary Fiber; Dimethylhydrazines; Male; Neoplasms, Experimental; Pectins; Rats