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.

ACKNOWLEDGMENTS

We do not have any financial conflicts. We want to thank University of Oklahoma Health Sciences Center Rodent Barrier Facility staff. We also want to thank Dr. Julie Sando for valuable suggestions and editorial help and acknowledge support from the National Cancer Institute, N01CN-53300, and Kerley Cade Endowed Chair.