Reduction of Visceral and Body Fats in Mice by Supplementation of Conjugated Linoleic Acid with γ-Oryzanol

Jang

et al. 2010

The protective effect of c9,t11-conjugated linoleic acid (CLA) on the inhibition of gap junctional intercellular communication (GJIC) was examined in a human mammary epithelial cell line (MCF-10A) treated with 12-O-tetradecanoylphorbol-13-acetate (TPA), relative to t10,c12-CLA isomer. TPA inhibited GJIC in a dose-dependent and reversible manner and was associated with connexin 43 phosphorylation. Pretreatment of 20 μM c9,t11-CLA for 24 h prior to 60 nM TPA for 1 h prevented the inhibition of GJIC by reducing the phosphorylation of connexin 43 via suppressing extracellular signal-regulated kinases (ERK1/2) activation. Reactive oxygen species (ROS) accumulation by TPA was attenuated by c9,t11-CLA. The efficacy of c9,t11-CLA in protecting inhibition of GJIC, connexin 43 phosphorylation, and ROS production was superior to that of t10,c12-CLA. These results suggest that c9,t11-CLA, including t10,c12-CLA, prevents the carcinogenesis of MCF-10A cells by protecting down-regulation of GJIC during the cancer promotion stage, and lack of their toxicities could be an excellent indicator for the chemoprevention of breast cancer.

Section: Introductionmentioning

confidence: 99%

Attenuation of 12-O-Tetradecanoylphorbol-13-acetate (TPA)-Induced Gap Junctional Intercellular Communication (GJIC) Inhibition in MCF-10A Cells by c9,t11-Conjugated Linoleic Acid

Rakib

Jang

et al. 2010

“…CLA, which is synthesized from linoleic acid (LA) by alkaline isomerization, contains all possible CLA isomers: t 10, c 12-CLA and c 9, t 11-CLA are major isomers , , and t , t -CLA, containing t 7, t 9-, t 8, t 10-, t 9, t 11-, t 10, t 12-, t 11, t 13-, and t 12, t 14-CLA isomers, are minor constituents . CLA has shown potent anticancer activity for carcinogen-induced carcinogenesis in several animals and human cancer cells , as well as exhibiting other biological activities , . The anticarcinogenic potentials of CLA and its individual isomers, t 10, c 12-CLA and c 9, t 11-CLA, have been extensively studied , .…”

Section: Introductionmentioning

confidence: 99%

Differential Inhibitory Effects of Conjugated Linoleic Acid Isomers on Mouse Forestomach Neoplasia Induced by Benzo(a)pyrene

Kim²,

et al. 2010

The differential anticarcinogenic activity of conjugated linoleic acid (CLA) isomers, including c9,t11-CLA, t10,c12-CLA, and t,t-CLA, was examined in a mouse forestomach carcinogenesis regimen induced by benzo(a)pyrene (BP). Female ICR mice (6-7 weeks of age, 26 +/- 1 g) were divided into six groups (30 mice/group, 5 mice/cage): control, linoleic acid, CLA, c9,t11-CLA, t10,c12-CLA, and t,t-CLA. Each mouse was orally given 0.1 mL of sample and 0.1 mL of olive oil on Monday and Wednesday and BP (2 mg in 0.2 mL of olive oil) on Friday. This cycle was repeated four times. Twenty-three weeks later, the experiment was terminated for tumor analysis. t,t-CLA significantly reduced (p < 0.05) both tumor number and tumor size per mouse, relative to CLA and c9,t11-CLA, but similar to t10,c12-CLA. Reduction in tumor incidence by t,t-CLA (84.6%) was similar to that by CLA, c9,t11-CLA, and t10,c12-CLA, but it was significantly reduced (p < 0.05), relative to 100% linoleic acid and control. t,t-CLA elevated the apoptotic index to 35%, relative to 23% for CLA, 21% for c9,t11-CLA, 29% for t10,c12-CLA, 7% for linoleic acid, and 4% for control. t,t-CLA up-regulated the expression of the Bax gene and activated caspase-3 enzymes but down-regulated expression of the Bcl-2 gene. Cytosolic phospholipase A(2) activity was not affected by the CLA isomers tested. These results suggest that t,t-CLA has superior anticarcinogenic potential on BP-induced mouse forestomach neoplasia to CLA, c9,t11-CLA, and t10,c12-CLA, via the induction of apoptosis through mitochondrial dysfunction.

“…9,16 Conjugated linoleic acid (CLA) is a group of positional (7,9; 8,10; 9,11; 10,12; 11,13; and 12,14) and geometrical (cis,trans; trans,cis; cis,cis; and trans,trans) isomers of octadecanoic acid (C18:2) with a conjugated double-bond system. Since its discovery in fried ground beef, 17 CLA has gained attention because of its important biofunctional activities, especially for its anticarcinogenic 18 and body fat reduction 19 properties. In synthetic CLA, c9,t11-CLA and t10,c12-CLA isomers predominate and t9, t11-CLA and t10,t12-CLA are present as minor components.…”

Section: ' Introductionmentioning

confidence: 99%

Preventive Effect of t,t-Conjugated Linoleic Acid on 12-O-Tetradecanoylphorbol-13-acetate-Induced Inhibition of Gap Junctional Intercellular Communication in Human Mammary Epithelial MCF-10A Cells

Rakib

Jang

et al. 2011

The anti-tumor promotional effects of t9,t11-conjugated linoleic acid (t9,t11-CLA) and t10,t12-CLA were evaluated on the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inhibition of gap junctional intercellular communication (GJIC) in the human mammary epithelial cell line MCF-10A. The results were compared to those obtained from c9,t11-CLA, which is a more effective anti-tumor promoter on TPA-induced GJIC inhibition in MCF-10A cells than t10,c12-CLA. Cells were treated with 20 μM t9,t11-CLA, t10,t12-CLA, or c9,t11-CLA for 24 h followed by 60 nM TPA for 1 h. Both t9,t11-CLA and t10,t12-CLA equally protected MCF-10A cells from TPA-induced inhibition of GJIC with inferior efficacy to c9,t11-CLA.The protection was due to the ameliorated phosphorylation of connexin43 via suppression of extracellular signal-regulated kinases (ERK1/2) activation. Suppression of TPA-induced reactive oxygen species (ROS) generation by t9,t11-CLA and t10,t12-CLA was less effective, relative to c9,t11-CLA. The results suggest that the anti-promotional activities of t9,t11-CLA and t10,t12-CLA are equal but less potent than c9,t11-CLA in TPA-treated MCF-10A cells. The activity might be mediated by the attenuation of ROS production in MCF-10A cells by preventing the downregulation of GJIC during the cancer promotion stage.