Dietary conjugated linoleic acid increases the mRNA ratio of Bax/Bcl-2 in the colonic mucosa of rats.
Previously we have shown that dietary conjugated linoleic acid (CLA) significantly decreased colon tumor incidence in rats injected with 1,2-dimenthylhydrazine (DMH). The present study was performed to explore the mechanisms responsible for the anticarcinogenic effect of CLA. Four groups of rats received either vehicle or intramuscular injections of DMH at the dose of 15 mg/kg body weight twice per week for 6 weeks and were fed a diet containing either 0% or 1.0% CLA ad libitum for 14 weeks. Dietary CLA decreased cellular proliferation and induced apoptosis in the colonic mucosa of both vehicle and DMH-treated rats. Mucosal levels of prostaglandin (PG) E(2), thromboxane B(2), and 1,2-diacylglycerol decreased in rats fed the 1% CLA diet, whereas cyclooxygenase-2 levels were not affected. Arachidonate content of mucosal phospholipids decreased significantly in rats fed the 1% CLA diet. Reverse transcriptase-polymer chain reaction analysis revealed that the Bax/Bcl-2 transcript ratio was significantly increased in rats fed 1% CLA. To examine whether the 1% CLA diet reduces tumor incidence, the DMH-treated rats were continuously fed the assigned diets for 30 weeks. Tumor incidence was significantly decreased in the CLA-fed group. In conclusion, our findings are consistent with the hypothesis that CLA decreases the incidence of colon cancer by decreasing cellular proliferation and inducing apoptosis of the colonic mucosa. These effects may be due in part to decreased PGE(2) levels and increased Bax/Bcl-2 ratios.
Park
Hyun S
HS
Department of Food and Nutrition, Kyung Hee University, Seoul, South Korea. jyoon@hallym.ac.kr
Cho
Hye Y
HY
Ha
Yeong L
YL
Park
Jung H Y
JH
D019813:1,2-Dimethylhydrazine; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016718:Arachidonic Acid / Q000032:analysis; D002455:Cell Division / Q000187:drug effects; D003106:Colon; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000517:prevention & control; D051546:Cyclooxygenase 2; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage*; D004075:Diglycerides / Q000032:analysis; D015232:Dinoprostone / Q000032:analysis; D019254:Genes, bcl-2 / Q000235:genetics*; D007413:Intestinal Mucosa / Q000737:chemistry*; D044243:Linoleic Acids, Conjugated / Q000008:administration & dosage*; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013929:Thromboxane B2 / Q000032:analysis; D051028:bcl-2-Associated X Protein
C011439:1,2-diacylglycerol; C494828:Bax protein, rat; D004042:Dietary Fats, Unsaturated; D004075:Diglycerides; D044243:Linoleic Acids, Conjugated; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D016718:Arachidonic Acid; D013929:Thromboxane B2; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D019813:1,2-Dimethylhydrazine; D015232:Dinoprostone