9trans,11trans conjugated linoleic acid inhibits the development of azoxymethane-induced colonic aberrant crypt foci in rats.
We investigated the effects of 9trans,11trans (9t,11t)-conjugated linoleic acid (CLA) isomer on azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in rats. Male F344 rats were given 2 weekly subcutaneous injections of AOM (20 mg/kg bw) to induce colonic ACF. They also were fed a diet containing either 0.01%, 0.1%, or 1% 9t,11t-CLA for 4 wk starting 1 wk before the first dosing of AOM. The group that received a diet supplemented with 9t,11t-CLA had a significantly lower number of ACF/colon in comparison to the AOM alone group in a dose-dependent manner up to 0.1%. Furthermore, treatment with 9t,11t-CLA induced apoptosis and suppressed cell proliferation activity in the non-lesional crypts. The downregulation of cyclooxygenase-2 and cyclin D1 and the activation of peroxisome proliferators activated receptor gamma were observed in the colonic mucosa of rats fed a diet supplemented with 9t,11t-CLA. Our findings thus provide some novel insight into the chemopreventive effect of 9t,11t-CLA against preinitiation as well as postinitiation stages of colorectal carcinogenesis.
Yasui
Yumiko
Y
Department of Oncologic Pathology, Kanazawa Medical University, Ishikawa, Japan. y-yasui@kanazawa-med.ac.jp
Suzuki
Rikako
R
Kohno
Hiroyuki
H
Miyamoto
Shingo
S
Beppu
Fumiaki
F
Hosokawa
Masashi
M
Miyashita
Kazuo
K
Tanaka
Takuji
T
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001397:Azoxymethane / Q000633:toxicity; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D003106:Colon / Q000737:chemistry / Q000187:drug effects / Q000473:pathology*; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000453:epidemiology / Q000378:metabolism / Q000517:prevention & control*; D019938:Cyclin D1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008055:Lipids / Q000032:analysis; D008297:Male; D047495:PPAR gamma / Q000378:metabolism; D011230:Precancerous Conditions / Q000139:chemically induced / Q000453:epidemiology / Q000378:metabolism / Q000517:prevention & control*; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344
D014408:Biomarkers, Tumor; D044243:Linoleic Acids, Conjugated; D008055:Lipids; D047495:PPAR gamma; D019938:Cyclin D1; D051546:Cyclooxygenase 2; D001397:Azoxymethane