Dietary conjugated linoleic acid (CLA) induces apoptosis of colonic mucosa in 1,2-dimethylhydrazine-treated rats: a possible mechanism of the anticarcinogenic effect by CLA

Abstract

One of the objectives of the present study was to investigate whether 1 % conjugated linoleic acid (CLA) in the diet reduced tumour incidence in the colon of 1,2-dimethylhydrazine (DMH)-treated rats. Colon cancer was induced by injecting 6-week-old, male, Sprague -Dawley rats with 15 mg/kg DMH twice per week for 6 weeks. They were fed either 1 % CLA or a control diet ad libitum for 30 weeks. Dietary CLA significantly decreased colon tumour incidence (P,0 : 05). Our second objective was to investigate whether apoptosis in the colon mucosa of DMH-treated rats was affected by the amount of dietary CLA and whether the changes in apoptosis were related to those in fatty acid-responsive biomarkers. For this purpose, rats were killed after being fed a diet containing 0 %, 0 : 5 %, 1 % or 1 : 5 % CLA for 14 weeks. CLA was undetected in the mucosa of rats fed the 0 % CLA diet and increased to 5 : 9 mg/g phospholipid in rats fed the 0 : 5 % diet. The apoptotic index estimated by the terminal deoxynucleotidyl transferase-mediated dUTP nick and labelling technique was increased by 251 % and the 1,2-diacylglycerol content was decreased by 57 % in rats fed 0 : 5 % CLA. No further changes in these variables were observed when CLA in the diet was raised to 1 : 0 % or 1 : 5 %. However, dietary CLA decreased mucosal levels of prostaglandin E 2 , thromboxane B 2 and arachidonic acid in a dose-dependent manner. The present data indicate that dietary CLA can inhibit DMH-induced colon carcinogenesis by mechanisms probably involving increased apoptosis.

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

“…CLA treatment inhibits the formation of colonic 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-DNA adducts and putative precancerous ACF in colon. 18 Recently, Park et al 37 reported that dietary CLA can inhibit 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis through possibly induction of apoptosis. Cell proliferation is known to play an important role in multistage carcinogenesis with multiple genetic changes.…”

“…CLA is known to be a possible chemopreventive agent against ACF formation 18,19 and colon carcinogenesis. 37 Whereas CLA used in published studies 15,17,35,39 contains a mixture of positional and geometrical iso- mers, c9,t11-18:2 isomer is considered to be the active constituent. Therefore, the suppressing effect of BMO on colon carcinogenesis in the current study may be attributed to c9,t11-18:2 isomer derived from c9,t11,t13-18:3 in the BMO diets.…”

Os efeitos do ácido linoléico conjugado no metabolismo animal: avanço das pesquisas e perspectivas para o futuro

“…Em 2001, Park et al 48 , estudando câncer de cólon induzido por dimetilhidrazina em ratos, demonstraram que a redução da incidência do câncer está relacionada com o aumento do índice apoptótico. Posteriormente, o mesmo grupo demonstrou que o aumento do índice apoptótico estaria relacionado, em parte, com a redução de prostaglandinas E2, acompanhada do aumento da razão das proteínas pró-apoptóticas Bax/Bcl-2, como foi observado pelos autores 49 .…”

Intake of dairy products and risk of colorectal neoplasia

“…Studies in cell lines have shown that CLA inhibits the growth of a variety of tumour cells (95 -97) . Dietary CLA has also been shown to reduce colon cancer incidence in animals administered a colorectal carcinogen (98) . In a human epidemiological study in which CLA intakes were estimated, high CLA intakes were associated with a reduced risk of CRC; the RR associated with the highest v. the lowest quartile of intake was 0·71 (95 % CI 0·55, 0·91; P for trend ¼ 0·004) (99) .…”