Dietary seed oil rich in conjugated linolenic acid from bitter melon inhibits azoxymethane-induced rat colon carcinogenesis through elevation of colonic PPARgamma expression and alteration of lipid composition.
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) gamma 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 PPARgamma protein level in the colon mucosa.
Kohno
Hiroyuki
H
First Departments of Pathology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa, Japan. h-kohno@kanazawa-med.ac.jp
Yasui
Yumiko
Y
Suzuki
Rikako
R
Hosokawa
Masashi
M
Miyashita
Kazuo
K
Tanaka
Takuji
T
D000230:Adenocarcinoma / Q000139:chemically induced / Q000517:prevention & control; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001397:Azoxymethane / Q000633:toxicity*; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D004041:Dietary Fats / Q000494:pharmacology*; D015994:Incidence; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008297:Male; D029777:Momordica charantia; D008517:Phytotherapy; D010938:Plant Oils; D051381:Rats; D011916:Rats, Inbred F344; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000235:genetics*; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics*
D016588:Anticarcinogenic Agents; D004041:Dietary Fats; D044243:Linoleic Acids, Conjugated; D010938:Plant Oils; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D001397:Azoxymethane