Induction of apoptosis by c9, t11-CLA in human endometrial cancer RL 95-2 cells via ERα-mediated pathway.
Numerous studies have shown that conjugated linoleic acid (CLA) can inhibit cancer cells growth and induce apoptosis in vitro and in vivo. The aim of the present study was to investigate the effects of CLA, including cis9, trans11-conjugated linoleic acid (c9, t11-CLA) and trans10, cis12-conjugated linoleic acid (t10, c12-CLA), on apoptosis of human endometrial cancer RL 95-2 cells and its related mechanisms. The MTT analysis was used to evaluate the effect of CLA isomers on the viability of endometrial cancer RL 95-2 cells. We then estimated the apoptosis by Morphological observation and Annexin V-FITC/PI staining and flow cytometry. We also used Western blot analysis to assess the expression of caspase-3, Bax, Bcl-2 proteins and the activation of Akt/p-Akt and ERα/p-ERα. Propylpyrazole-triol (PPT), a selective ERα agonist was used to confirm the induction of apoptosis by c9, t11 CLA may relate to ERα-mediated pathway. In CLA-treated RL 95-2 cells, we found that c9, t11-CLA inhibited viability and trigged apoptosis, as judged from nuclear morphology and flow cytometric analysis. The expression of caspase-3 and the ratio of Bax/Bcl-2 were significant increased, but no obvious change was observed about Akt and p-Akt in c9, t11-CLA-treated cells. However, the expression of total ERα level in RL 95-2 cells-treated with c9, t11-CLA was unchanged, while in the concentration of 80 mM, c9, t11-CLA down-regulated the protein expression level of p-ERα. Then PPT has the antagonistic action on growth inhibitory effect in RL 95-2 cells incubated with c9, t11-CLA. This study demonstrated that c9, t11- CLA could induce apoptosis in RL 95-2 cells, and may involve in ERα-mediated pathway. These results indicated that c9, t11- CLA could induce apoptosis of endometrial cancer cells and may be potential agents for the treatment of endometrial cancer.
Apoptosis; Conjugated linoleic acid; Endometrial cancer; Estrogen receptor
- PMID: 23954748
Choose Life Notes : When my daughter was born extremely prematurely, I was aware of this acid from studies showing it is found in around 50% higher amounts in mothers breast milk who are eating (almost) exclusively organic vs non-organic, women’s breast milk was tested and it showed that their milk was also many fold richer in this heavyweight nutrient. We had grass fed raw Milk (knowing this also increased the amounts by potentially 300-500%) and the Weston Price based formula of High Vitamin Butter Oil and Fermented Cod Liver Oil (not personally as vegetarian, but I encouraged my wife daily to take this through pregnancy and the lactation period).
This formula, which I believe Weston Price referred to as ActivatorX, bears striking similarity to Johanna Budwigs Flax and Cottage Cheese blend, both are 2-1 Omega 6:3.
This research shows that CLA C9 T11 was found in the highest amounts in short fermented organic milk:
Increased CLA content in organic milk fermented by bifidobacteria or yoghurt cultures | Request PDF. Available from: https://www.researchgate.net/publication/44844024_Increased_CLA_content_in_organic_milk_fermented_by_bifidobacteria_or_yoghurt_cultures [accessed Sep 14 2018].
Choose Life Notes : This highlights the potential importance of Grass Fed Raw Kefir as the Sulfur Protein element in the Budwig Protocol, also within the GC Maf protein mixtures, adopting a best attainable approach, we latterly used to get A2 Raw Milk from Hurdlebrook Farm, they are converting to Organic now, perhaps we will start buying from there again, and make some kefir, as my wife has just started working near by again, serendipitously.
Atherosclerosis, the underlying cause of heart attack and strokes, is a progressive dyslipidaemic and inflammatory disease where monocyte-derived macrophage cells play a pivotal role. Although most of the mechanisms that contribute to the progression of atherosclerosis have been identified, there is limited information on those governing regression. Conjugated linoleic acid (CLA) is a generic term denoting a group of naturally occurring isomers of linoleic acid (18:2, n6) that differ in the position or geometry (i.e. cis or trans) of their double bonds. The most predominant isomers in ruminant fats are cis-9, trans-11 CLA (c9,t11-CLA), which accounts for more than 80% of CLA isomers in dairy products and trans-10, cis-12 CLA (t10,c12-CLA). Dietary administration of a blend of the two most abundant isomers of CLA has been shown to inhibit the progression and induce the regression of pre-established atherosclerosis. Studies investigating the mechanisms involved in CLA-induced atheroprotective effects are continually emerging. The purpose of this review is to discuss comprehensively the effects of CLA on monocyte/macrophage function in atherosclerosis and to identify possible mechanisms through which CLA mediates its atheroprotective effects.
atherosclerosis; conjugated linoleic acid; inflammation; resolution.
Selective effect of conjugated linoleic acid isomers on atherosclerotic lesion development in apolipoprotein E knockout mice.
Research suggests that conjugated linoleic acid (CLA) may inhibit atherosclerosis, but there are contradictory results in different animal models fed heterogeneous mixtures of CLA isomers. This study addressed the hypothesis that the individual CLA isomers may exert different atherogenic properties. ApoE(-/-) mice were fed isocaloric, isonitrogenous westernized diets containing 0.15% cholesterol and enriched with 1% (w/w) cis-9,trans-11-CLA (c9,t11-CLA), trans-10,cis-12-CLA (t10,c12-CLA) or linoleic acid (control diet) for 12 weeks. At the end of the dietary intervention, the effects of CLA isomers on the development of atherosclerotic vascular lesions, lipid metabolism, inflammation and oxidative stress were assessed. The t10,c12-CLA diet had a profound pro-atherogenic effect, whereas c9,t11-CLA impeded the development of atherosclerosis. En face aortic lesion assessment showed more dorsal and lumbar extensions presenting atherosclerotic foci after the t10,c12-CLA diet. Furthermore, animals fed t10,c12-CLA had pronounced hyperlipidemia, higher 8-iso-prostaglandin F(2alpha) levels, higher vulnerable atherosclerotic plaque with a lower smooth muscle and fibre contents and higher macrophage content and activation, assayed as plasma chitotriosidase compared to the control or c9,t11-CLA dietary groups. Plasma chitotriosidase activity was more closely associated with the extent of the plaque than with MOMA staining or than monocyte chemoattractant protein-1 levels.
Our results demonstrate that CLA isomers differentially modulate the development of atherosclerosis, c9,t11-CLA impedes, whereas t10,c12-CLA promotes atherosclerosis. These opposing effects may be ascribed to divergent effects on lipid, oxidative, inflammatory and fibro muscular components of this pathology. Plasma chitotriosidase is a better indicator of dietary fat interventions that alter plaque monocyte activity in this murine model.
c9,t11-Conjugated linoleic acid ameliorates steatosis by modulating mitochondrial uncoupling and Nrf2 pathway.
Oxidative stress, hepatic steatosis, and mitochondrial dysfunction are key pathophysiological features of nonalcoholic fatty liver disease. A conjugated linoleic acid (CLA) mixture of cis9,trans11 (9,11-CLA) and trans10,cis12 (10,12-CLA) isomers enhanced the antioxidant/detoxifying mechanism via the activation of nuclear factor E2-related factor-2 (Nrf2) and improved mitochondrial function, but less is known about the actions of specific isomers. The differential ability of individual CLA isomers to modulate these pathways was explored in Wistar rats fed for 4 weeks with a lard-based high-fat diet (L) or with control diet (CD), and, within each dietary treatment, two subgroups were daily administered with 9,11-CLA or 10,12-CLA (30 mg/day). The 9,11-CLA, but not 10,12-CLA, supplementation to CD rats improves the GSH/GSSG ratio in the liver, mitochondrial functions, and Nrf2 activity. Histological examination reveals a reduction of steatosis in L-fed rats supplemented with both CLA isomers, but 9,11-CLA downregulated plasma concentrations of proinflammatory markers, mitochondrial dysfunction, and oxidative stress markers in liver more efficiently than in 10,12-CLA treatment.
The present study demonstrates the higher protective effect of 9,11-CLA against diet-induced pro-oxidant and proinflammatory signs and suggests that these effects are determined, at least in part, by its ability to activate the Nrf2 pathway and to improve the mitochondrial functioning and biogenesis.
fatty acids; mitochondrial efficiency; nuclear factor E2-related factor-2
- PMID: 2463450