"Chemopreventive Effects of Omega-3 Fatty Acid and Lignans Present in F" by Ajay Bommareddy

Document Type

Thesis - University Access Only

Award Date

2007

Degree Name

Doctor of Philosophy (PhD)

Department / School

Biology

Abstract

Fatty acid composition of dietary fat plays a vital role in colon tumor development in animal models. Fats containing co-6 fatty acids (e.g., com oil) enhanced, and co-3 fatty acids (e.g., flaxseed oil) reduced chemically-induced colon tumor development in rats. Lignans have also been shown to prevent colon tumor development in experimental animals. The objective of the present investigation was to study the effects of dietary flaxseed meal, a source of both co-3 fatty acid and lignans on colon tumor development in male Fischer rats and APC Min mice, and also investigate the role of these active components present in flaxseed (alpha-linolenic acid, enterodiol and enterolactone) on human colon tumor CAC0-2 cell line. Male Fischer rats, two groups of 24 each were assigned to the AIN-93M diet supplemented with either 15% com meal or 15% flaxseed meal respectively. Carcinogensis was initiated with subcutaneous injections of azoxymethane (15mg/kg) once a week for three consecutive weeks. After 35 weeks of initiation, rats were anesthetized with ether. APC min mice, five groups of 8 each were assigned to AIN-93 M diet, AIN-93 M diet supplemented with 15% flaxseed oil, flaxseed meal, com oil and com meal respectively for 12 weeks. Blood was collected by cardiac puncture, rats and mice were sacrificed. The gastrointestinal tract from rats and mice were isolated. The site, size and number of tumors were recorded. The fatty acid analyses of the collected serum, intestine and colon samples were performed. Expression of COXI and COX-2 was performed by Western blot method. Lignan levels in serum, intestine and colon samples were assayed. Tumor incidence and multiplicity was significantly (p<0.05) lower in dietary flaxseed meal group in male Fischer rats experiment whereas 100% incidence was observed in all the groups in APC Min mice experiment, However tumor multiplicity was significantly (p<0.05) lower in dietary flaxseed meal group compared to untreated groups in both Fischer rats and APC Min mice. Intestine, Colon and serum samples of the com meal group showed higher levels of ro-6 fatty acids levels whereas the flaxseed meal group exhibited higher levels of ro-3 fatty acid levels. COX-I and COX-2 expression in flaxseed group was significantly lower (p<0.05) as compared to com group. Cell culture studies showed a significant {p<0.05) increase in apoptotic cells and decrease in cell proliferation when treated with various concentrations of experimental compounds (alpha-linolenic acid, enterodiol and enterolactone) present in flaxseed. Dietary flaxseed meal containing high levels of ro-3 fatty acids and lignans is effective in preventing intestinal and colon tumor development when compared with dietary com meal possibly by increasing ro-3 fatty acid levels, lignans and decreasing COX-1 and COX-2 levels. Alpha-linolenic acid, enterodiol and enterolactone decrease cell proliferation and increase apoptosis. Dietary flaxseed could be effective chemopreventive agent for intestinal and colon tumor development.

Library of Congress Subject Headings

Flaxseed
Omega-3 fatty acids
Lignans
Colon (Anatomy) -- Tumors -- Chemoprevention
Colon (Anatomy) -- Tumors -- Animal models

Format

application/pdf

Number of Pages

117

Publisher

South Dakota State University

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