• Journal of the Korean Society of Food Science and Nutrition
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• v.20 no.4
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• pp.401-407
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• 1991

Anticarcinogenic conjugated dienoic derivatives of linoleic acid (CLA) is present in grilled beef, cheese, and related foods, CLA is generated via isomerization of linoleic acid in the cow's rumen by anaerobic bacteria and food proceessing as well. Another source of CLA is its endogenous generation via the carbon centered free radical oxdation of linoleic acid. We propose that the formation and generation of CLA in vivo represents a previously unrecognized in situ "defense mechanism" against membrane attack by oxygen free radicals. The cis, 9-trans, 11 CLS isomer is selectively incorporated into cellular phospholipid, which exhibits a potent antioxidant, reduces the activation of 2-amino-3-methylimidazo, [4,5-f] quinoline (IQ) for baxterial mutagenesis, and inhibits ornithine decarboxylase(ODC) activity induced by 12-0-tetradecanoylphorbol-13-acetate (TPA). We believe that at least these biological activities of CLA explain the anticarcinogenic activity of CLA.

• Biomolecules & Therapeutics
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• v.23 no.2
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• pp.134-140
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• 2015

Conjugated linoleic acids (CLA) are a family of isomers of linoleic acid. CLA increases growth arrest and apoptosis of human colorectal cancer cells through an isomer-specific manner. ATF3 belongs to the ATF/CREB family of transcription factors and is associated with apoptosis in colorectal cancer. The present study was performed to investigate the molecular mechanism by which t10, c12-CLA stimulates ATF3 expression and apoptosis in human colorectal cancer cells. t10, c12-CLA increased an apoptosis in human colorectal cancer cells in dose dependent manner. t10, c12-CLA induced ATF3 mRNA and luciferase activity of ATF3 promoter in a dose-dependent manner. The responsible region for ATF3 transcriptional activation by t10, c12-CLA is located between -147 and -1850 of ATF3 promoter. mRNA stability of ATF3 was not affected by t10, c12-CLA treatment. t10, c12-CLA increases $GSK3{\beta}$ expression and suppresses IGF-1-stimulated phosphorylation of Akt. The knockdown of ATF3 suppressed expression of $GSK3{\beta}$ and NAG-1 and PARP cleavage. The results suggest that t10, c12-CLA induces apoptosis through ATF3-mediated pathway in human colorectal cancer cells.

• Journal of Nutrition and Health
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• v.35 no.2
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• pp.192-200
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• 2002

Conjugated linoleic acid (CLA) is a collective term for positional and geometric isomers of octadecadienoic acid in which the double bonds are conjugated. CLA has anticancer activity in a variety of animal cancer models, and cis-9, trans-11 (c9t11) and trans-10, cis-12(t10c12) CLA are the most predominant isomers present in the synthetic preparations utilized in these animal studies. To compare the ability of c9t11, t10c12 and an isomeric mixture of CLA to inhibit TSU-Prl cell growth, cells were incubated in a serum-free medium with various concentrations of these fatty acids. The isomeric mixture inhibited cell growth in a dose-dependent manner (1-3 $\mu$M) with a 41 $\pm$ 1% inhibition observed at 3 $\mu$M concentration after 48 hours. T10c12 also inhibited cell proliferation in a dote-dependent manner, However, the efficacy and potency of this isomer was much greater than that of the isomeric mixture with a 49 $\pm$ 2% inhibition observed at 0.3 $\mu$M concentration after 48 hours. By contrast, c9t11 slightly increased cell proliferation. To determine whether the growth-inhibiting effect of CLA is related to the changes in production of insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP) by these cells, serum-free conditioned media were collected. Immunoblot analysis of conditioned media using a monoclonal anti-IGF-II antibody showed that both the isomeric mixture and t10c12 inhibited secretion of both mature 7,500 Mr and higher Mr forms of pro IGF-II, whereas c9t11 had no effect. Ligand blot analysis with 125I-IGF-II revealed the presence of two types of IGFBPs : 24,000 Mr IGFBP-4 and 30,000 Mr IGFBP-6. The production of IGFBP-4 slightly decreased at the highest concentrations of the isomeric mixture and t10c12. These results indicate that CLA inhibits human prostate cancer cell growth, an effect largely due to the action of t10c12. The growth inhibition may result, at least in part, from decreased production of IGF-II and IGFBP-4 by these cells.

• Asian-Australasian Journal of Animal Sciences
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• v.16 no.2
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• pp.306-314
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• 2003

Bio-hydrogenation of $C_{18}$-unsaturated fatty acids released from the hydrolysis of dietary lipids in the rumen, in general, occurs rapidly but the range of hydrogenation is quite large, depending on the degree of unsaturation of fatty acids, the configuration of unsaturated fatty acids, microbial type and the experimental condition. Conjugated linoleic acid (CLA) is incompletely hydrogenated products by rumen microorganisms in ruminant animals. It has been shown to have numerous potential benefits for human health and the richest dietary sources of CLA are bovine milk and milk products. The cis-9, trans-11 is the predominant CLA isomer in bovine products and other isomers can be formed with double bonds in positions 8/10, 10/12, or 11/13. The term CLA refers to this whole group of 18 carbon conjugated fatty acids. Alpha-linolenic acid goes through a similar bio-hydrogenation process producing trans-11 $C_{18:1}$ and $C_{18:0}$, but may not appear to produce CLA as an intermediate. Although the CLA has been mostly derived from the dietary $C_{18:2}$ alternative pathway may be existed due to the extreme microbial diversity in the reticulo-rumen. Regardless of the origin of CLA, manipulation of the bio-hydrogenation process remains the key to increasing CLA in milk and beef by dietary means, by increasing rumen production of CLA. Although the effect of oil supplementation on changes in fatty acid composition in milk seems to be clear its effect on beef is still controversial. Thus further studies are required to enrich the CLA in beef under various dietary and feeding conditions.