Dietary seed oil rich in conjugated linolenic acid from bitter melon inhibits azoxymethane‐induced rat colon carcinogenesis through elevation of colonic PPARγ expression and alteration of lipid composition

Abstract

Our previous short-term experiment demonstrated that seed oil from bitter melon (Momordica charantia) (BMO), which is rich in cis(c)9, trans(t)11, t13-conjugated linolenic acid (CLN), inhibited the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF). In our study, the possible inhibitory effect of dietary administration of BMO on the development of colonic neoplasms was investigated using an animal colon carcinogenesis model initiated with a colon carcinogen AOM. Male F344 rats were given subcutaneous injections of AOM (20 mg/kg body weight) once a week for 2 weeks to induce colon neoplasms. They also received diets containing 0.01%, 0.1% or 1% BMO for 32 weeks, starting 1 week before the first dosing of AOM. At the termination of the study (32 weeks), AOM induced 83% incidence (15/18 rats) of colonic adenocarcinoma. Dietary supplementation with 0.01% and 0.1% BMO caused significant reduction in the incidence (47% inhibition by 0.01% BMO, p<0.02; 40% inhibition by 0.1% BMO, p<0.05; and 17% inhibition by 1% BMO) and the multiplicity (64% inhibition by 0.01% BMO, p<0.005; 58% inhibition by 0.1% BMO, p<0.02; and 48% inhibition by 1% BMO, p<0.05) of colonic adenocarcinoma, though a clear dose response was not observed. Such inhibition was associated with the increased content of CLA (c9,t11-18:2) in the lipid composition in colonic mucosa and liver. Also, BMO administration in diet enhanced expression of peroxisome proliferator-activated receptor (PPAR) ␥ protein in the nonlesional colonic mucosa. These findings suggest that BMO rich in CLN can suppress AOM-induced colon carcinogenesis and the inhibition might be caused, in part, by modification of lipid composition in the colon and liver and/or increased expression of PPAR␥ protein level in the colon mucosa.

Microbes, Immunity, and Behavior: Psychoneuroimmunology Meets the Microbiome

“…Conjugated fatty acids, natural components of milk and tissue fat from ruminants, plant seed oils, and marine algae are positional and geometric isomers of polyunsaturated fatty acids with one or more conjugated double bonds (Chisholm and Hopkins, 1967;Burgess et al, 1991;Kohno et al, 2004;Yasui et al, 2005). Of these conjugated linoleic acid (CLA) is the most extensively studied with multiple putative health benefits including an antiatherosclerotic effect, an antiobesogenic impact, and probable anticarcinogenic properties (Bassaganya-Riera et al, 2002; Belury, 2002; Ip et al, 2003).…”

Peroxisome Proliferator-Activated Receptor γ Pathway Targeting in Carcinogenesis: Implications for Chemoprevention

“…Another potentially useful chemopreventive therapeutic, 9,11-conjugated linoleic acid, has also been tested as a potential PPARg-activating treatment for the prevention of colon carcinogenesis. This agent is derived from bitter melons, and when administered in the diet of azoxymethane-treated Fischer rats, 50% decreases in tumor incidence and size were observed in the 9,11-conjugated linoleic acid-treated rats, and this was accompanied by an increase in the level of PPARg in colonic mucosa (44). Others have shown PPARg activation with 9,11-conjugated linoleic acid (45,46), and because PPARg is known to induce itself, this is a simple explanation for why elevated PPARg levels were observed.…”

Inhibition of Colon Carcinogenesis by Dietary Non-Nutritive Compounds

“…We should thus estimate the reported chemopreventive efficacy of non-nutritives in edible plants using both ACFs and these new lesions as biological markers for colon carcinogenesis in future studies. Since the ligands for PPARs can inhibit AOM-induced ACFs, which weakly express PPARγ 182 , we are now searching for natural compounds that act as ligands for PPARs 51,58,59 . In the near future, we would like to provide promising non-nutritive compounds (including citrus compounds, auraptene and nobiletin) with less toxicity from edible Asian plants 105,183,184 for use in clinical CRC chemoprevention trials.…”