Conjugated linoleic acid suppresses colon carcinogenesis in azoxymethane-pretreated rats with long-term feeding of diet containing beef tallow.
BACKGROUND
We have indicated previously that long-term feeding of beef tallow increases colorectal cancer in rats. In this study, we investigated the effects of conjugated linoleic acid (CLA) on colon carcinogenesis in rats under long-term feeding of beef tallow diets, pretreated with azoxymethane (AOM).


METHODS
Six-week-old male Sprague-Dawley rats were fed with 10% beef tallow diet only, 10% beef tallow with 1% CLA in triglyceride form (CLA-TG), or 10% beef tallow with 1% CLA in free fatty acid form (CLA-FFA). Colon carcinogenesis was induced by two intraperitoneal injections of AOM. Aberrant crypt foci (ACFs) were examined at 12 weeks. Cancer, cell proliferation, apoptosis, Wnt signaling, and the arachidonic acid cascade were examined at 44 weeks.


RESULTS
At 12 weeks, CLA-TG and CLA-FFA attenuated the increase in ACFs induced by 10% beef tallow and AOM pretreatment. At 44 weeks, both forms of CLA attenuated multiple colon cancers, and CLA-FFA reduced the incidence of colon cancer to 50% of that seen with CLA-TG. CLA-TG and CLA-FFA decreased the number of 5-bromo-2'-deoxyuridine-positive cells in AOM-pretreated rats fed with 10% beef tallow. CLA-FFA increased the number of apoptotic cells and the activity of caspase-3 in the colon mucosa, and CLA-TG enhanced the activity of caspase-3. Both forms of CLA suppressed Wnt signaling and the arachidonic acid cascade in rats treated with beef tallow and AOM.


CONCLUSIONS
These results suggested that CLA-TG and CLA-FFA suppressed colon carcinogenesis in rats with long-term feeding of a 10% beef tallow diet, through several mechanisms. The results of the present study with rats might be applicable to humans.
Department of Internal Medicine and Gastrointestinal Endoscopy, Saga Medical School, and Fujioka Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan.
Ryosuke
R
Shiraishi
Ryuichi
R
Iwakiri
Takehiro
T
Fujise
Tsukasa
T
Kuroki
Takashi
T
Kakimoto
Tooru
T
Takashima
Yasuhisa
Y
Sakata
Seiji
S
Tsunada
Yutaka
Y
Nakashima
Teruyoshi
T
Yanagita
Kazuma
K
Fujimoto
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016718:Arachidonic Acid / Q000378:metabolism; D001397:Azoxymethane / Q000633:toxicity*; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000209:etiology / Q000517:prevention & control*; D004041:Dietary Fats / Q000633:toxicity; D005223:Fats / Q000633:toxicity*; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008297:Male; D011230:Precancerous Conditions / Q000209:etiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D051153:Wnt Proteins / Q000187:drug effects / Q000378:metabolism
D004041:Dietary Fats; D005223:Fats; D044243:Linoleic Acids, Conjugated; D051153:Wnt Proteins; D016718:Arachidonic Acid; C013698:tallow; D001397:Azoxymethane