Superior Anticarcinogenic Activity of trans,trans-Conjugated Linoleic Acid in N-Methyl-N-nitrosourea-Induced Rat Mammary Tumorigenesis

Abstract

The anticarcinogenic activity of a mixture of trans,trans-conjugated linoleic acid (trans,trans-CLA) was investigated in rat mammary tumorigenesis induced by N-methyl-N-nitrosourea (MNU), with references to cis-9,trans-11-CLA and trans-10,cis-12-CLA isomers. Female, 7-week-old Sprague-Dawley rats were intraperitoneally injected with MNU (50 mg/kg of body weight) and then subjected to one of five diets (control, 1% trans,trans-CLA, 1% cis-9,trans-11-CLA, 1% trans-10,cis-12-CLA, and 1% linoleic acid; 8 rats/group) for 16 weeks. Food and water were made available ad libitum. trans,trans-CLA significantly (p < 0.05) reduced tumor incidence, number, multiplicity, and size and significantly (p < 0.05) increased apoptosis, relative to cis-9,trans-11-CLA and trans-10,cis-12-CLA. The molecular mechanism of trans,trans-CLA was elucidated by measuring apoptosis-related gene products and fatty acid composition in tumors. trans,trans-CLA led to increases in the p53 protein and Bax protein levels but suppressed the expression of Bcl-2 protein. The activation of caspase-3 led to the cleavage of poly(ADP-ribose) polymerase, which resulted in the execution of apoptosis. In addition, trans,trans-CLA reduced cytosolic phospholipase A2, cyclooxygenease-2, and peroxisome proliferator-activated receptor gamma protein levels. These results suggest that the trans,trans-CLA inhibits MNU-induced rat mammary tumorigenesis through the induction of apoptosis in conjunction with the reduction of arachidonic acid metabolites and that the efficacy of trans,trans-CLA is superior to cis-9,trans-11-CLA and trans-10,cis-12-CLA.

Effects of dietary conjugated linoleic acids on cellular immune response of piglets after cyclosporin A injection

“…CLA has many important properties that regulate physiological and metabolic responses, for example, immune modulation, anti-cancer effects, prevention of cardiovascular disease and diabetes, and weight control (Ip et al, 1991;Houseknecht et al, 1998;Islam et al, 2010;Eftekhari et al, 2013;Kim et al, 2013). In animal production, studies on the effects of CLA on immune function have thus far been conducted in the normal physiological status or inflammatory challenge status (O'Shea et al, 2004;Lai et al, 2005;Zhang et al, 2005;Renner et al, 2012).…”

Antiproliferative Action of Conjugated Linoleic Acid on Human MCF-7 Breast Cancer Cells Mediated by Enhancement of Gap Junctional Intercellular Communication through Inactivation of NF-κB

“…Numerous anticancer and anticarcinogenic effects of CLA and individual CLA isomers have been reported. CLA inhibits 7,12-dimethylbenz[ a ]anthracene-induced mouse skin carcinogenesis, benzo (a) pyrene-induced mouse forestomach tumorigenesis, 2-amino-3,4-dimethylimidazo[4,5- f ] quinoline-induced rat colonic carcinogenesis, and N -methyl- N -nitrosourea-induced rat mammary carcinogenesis [1, 2, 6, 7]. Individual CLA isomers also show anticancer effects by inducing apoptosis in animals and cancer cell lines [7–9], but their mechanisms of action are still unknown.…”

Trans‐18:1 and CLA Isomers in Rumen and Duodenal Digesta of Bulls Fed n‐3 and n‐6 PUFA‐Based Diets

“…Until now, predominantly two CLA isomers, cis-9,trans-11 CLA and trans-10,cis-12 CLA, have been shown to have biological activity including prevention of different types of cancer, cardiovascular health and improved immune response predominantly in animal models; however, in recent human studies inconsistent effects have been reported [6,7]. Very recently, it has also been shown that trans,trans CLA isomers (trans-9,trans-11 CLA, trans-10,trans-12 CLA) inhibit rat mammary tumorigenesis through the induction of apoptosis in conjunction with the reduction of arachidonic acid metabolites [8]. There is much evidence that the physiological properties of CLA are isomer specific with partly opposing effects [6][7][8].…”

“…Very recently, it has also been shown that trans,trans CLA isomers (trans-9,trans-11 CLA, trans-10,trans-12 CLA) inhibit rat mammary tumorigenesis through the induction of apoptosis in conjunction with the reduction of arachidonic acid metabolites [8]. There is much evidence that the physiological properties of CLA are isomer specific with partly opposing effects [6][7][8]. Ruminant meat, milk and their products are the major source of CLA in human diet [9,10].…”