Pectin does not inhibit intestinal carcinogenesis in APC-deficient Min/+ mice.
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.
Jacobasch
Gisela
G
Department of Food Chemistry and Preventive Nutrition, German Institute of Human Nutrition, Nuthetal, Germany. G.K.Jacobasch@t-online.de
Dongowski
Gerhard
G
Florian
Simone
S
Müller-Schmehl
Katrin
K
Raab
Barbara
B
Schmiedl
Detlef
D
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*
D000085:Acetates; D000970:Antineoplastic Agents; D002087:Butyrates; D005232:Fatty Acids, Volatile; D010368:Pectins; D051546:Cyclooxygenase 2