title: Prevention of familial adenomatous polyp development in APC min mice and azoxymethane-induced colon carcinogenesis in F344 Rats by ω-3 fatty acid rich perilla oil.
abstract: The present study explored the preventive effects of perilla oil, rich in α-linolenic acid, in rodent models of colon tumorigenesis. Six-week-old male F344 rats were fed diets containing 5% corn oil or 10 or 20% perilla oil. Colonic aberrant crypt foci (ACF) were induced by azoxymethane (AOM) and colonic ACF were evaluated. In familial adenomatous polyposis mode, APC(min) mice fed with 20% corn oil or perilla oil for 80 days and intestines were evaluated for polyps. Multiple colonic mucosal and polyp samples were assayed for the expression and activity of cyclooxygenase COX-isoforms. Dietary perilla oil produced a dose-dependent inhibition of AOM-induced colonic ACF formation (by 35-53%, P < 0.01-0.005) and reduced the number of foci with ≥ 4 crypts/focus (by 38-50%, P < 0.01-0.001) in F344 rats. Dietary perilla oil significantly inhibited development of small intestinal (>69%, P < 0.0001) and colon tumors (>52%, P < 0.03) in APC(min) mice. Administration of perilla oil produced lower levels of type-2 prostaglandins (38-53%) from COX-activities in polyps of APC(min) mice. These observations demonstrate that dietary perilla oil rich in ω-3 fatty acids possesses preventive activity against intestinal neoplastic lesions, both in FAP in genetically-predisposed tissues, as well as against chemically induced preneoplastic lesions in the colon.
authors.affiliation: Center for Cancer Prevention and Drug Development, Department of Medicine, Hem-Onc Section, PC Stephenson Cancer Center, Oklahoma City, Oklahoma 73104, USA. cv-rao@ouhsc.edu
authors.forename: Chinthalapally V
authors.initials: CV
authors.lastname: Rao
authors.forename: Jagan M R
authors.initials: JM
authors.lastname: Patlolla
authors.forename: Indrani
authors.initials: I
authors.lastname: Cooma
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Kawamori
authors.forename: Vernon E
authors.initials: VE
authors.lastname: Steele
mesh_terms: D058739:Aberrant Crypt Foci / Q000139:chemically induced / Q000473:pathology*; D011125:Adenomatous Polyposis Coli / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001397:Azoxymethane / Q000633:toxicity; D063646:Carcinogenesis / Q000139:chemically induced / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D003314:Corn Oil / Q000008:administration & dosage; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010938:Plant Oils / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D017962:alpha-Linolenic Acid / Q000494:pharmacology*
chemical_list: D016588:Anticarcinogenic Agents; D008565:Membrane Proteins; D010938:Plant Oils; D017962:alpha-Linolenic Acid; C058216:perilla seed oil; D003314:Corn Oil; C077623:Ptgs2 protein, mouse; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496512:Ptgs1 protein, mouse; C496513:Ptgs1 protein, rat; C489691:Ptgs2 protein, rat; D001397:Azoxymethane