title: Pectin does not inhibit intestinal carcinogenesis in APC-deficient Min/+ mice.
abstract: APC-germline mutation creates predisposition for intestinal tumorigenesis. APCMin/+ mice, developing tumors preferentially in the small intestine and only minimally in the colon, were fed pectin-enriched diets (10% galacturonan; degree of methoxylation=37.0 and 70.4%) or standard diet. Pectins used in the present study do not inhibit intestinal tumorigenesis and rather accelerate it in APCMin/+ mice. Both pectins exhibited prebiotic effects associated with high fermentative formation of acetate but producing low butyrate. The differences of the short-chain fatty acid concentrations between cecum and colon and those between colon and feces were larger than expected and increased with cancer progression, indicating an inhibition of butyrate absorption. Pectins transported more bile acids toward the colon than the standard diet and caused a higher generation of secondary bile acids despite lower pH values. Overexpression of COX-2 resulted in lower antioxidative capacity, thus promoting cancer. Apoptosis increased in hyperplasia but decreased in late adenomas. When biological modular design principles are taken into consideration, it can be expected that pectin also reinforces colorectal tumorigenesis of patients suffering from APC gene defects.
authors.affiliation: Department of Food Chemistry and Preventive Nutrition, German Institute of Human Nutrition, Nuthetal, Germany. G.K.Jacobasch@t-online.de
authors.forename: Gisela
authors.initials: G
authors.lastname: Jacobasch
authors.forename: Gerhard
authors.initials: G
authors.lastname: Dongowski
authors.forename: Simone
authors.initials: S
authors.lastname: Florian
authors.forename: Katrin
authors.initials: K
authors.lastname: Müller-Schmehl
authors.forename: Barbara
authors.initials: B
authors.lastname: Raab
authors.forename: Detlef
authors.initials: D
authors.lastname: Schmiedl
mesh_terms: D000085:Acetates / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002087:Butyrates / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005232:Fatty Acids, Volatile / Q000378:metabolism*; D005260:Female; D005285:Fermentation; D017491:Genes, APC / Q000502:physiology*; D018095:Germ-Line Mutation; D007150:Immunohistochemistry; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000473:pathology; D007414:Intestinal Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D010368:Pectins / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000085:Acetates; D000970:Antineoplastic Agents; D002087:Butyrates; D005232:Fatty Acids, Volatile; D010368:Pectins; D051546:Cyclooxygenase 2