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

Abstract

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.

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

“…MCF-7 cell proliferation was measured using the MTT assay as described previously [29]. Briefly, the cells treated with the CLA isomers were exposed to MTT solution (5 mg/mL of PBS) for 4 h. The MTT solution was removed, and 200  μ L DMSO was added to each well and mixed to dissolve the MTT formazan crystals formed by the viable cells.…”

“…GJIC of cells treated with CLA isomers was measured using the scrape loading/dye transfer (SL/DT) technique as previously described [29]. Briefly, cells were treated with 0.05% LY solution and scraped with a surgical steel scalpel blade at low light intensity.…”

“…Mutations or deficiencies in connexin genes are related to several diseases including cancer; thus, transfection of connexin genes into GJIC-deficient tumor cells restores the reduced GJIC and suppresses tumor growth [25–28]; therefore, connexin genes are related to restoration of GJIC in cancer cells. We previously demonstrated that CLA isomers prevent 12- O- tetradecanoylphorbol-13-acetate (TPA) induced downregulation of GJIC in non-tumorigenic mammary epithelial MCF-10A cells by inhibiting Cx43 phosphorylation [13, 29]. …”

Conjugated Linoleic Acid (CLA) Ameliorates Hydrogen Peroxide-Induced Oxidative Stress on Rat Cardiomyoblast H9c2 Cells

“…또한 심근경색은 섬유질이 많은 콩, 현미, 잡곡, 등푸른 생선, 딸기 등의 섭취로 예방할 수 있다 [4,28,30]. 최근 conjugated linoleic acid (CLA)는 1987년에 항암성 물질 로 개발 [11]된 이후, 항당뇨성, 항관절염성 등에 관하여 많은 연구가 수행되었다 [1,8,9,[11][12][13][14][15]21,22]. Lee (Fig.…”

Lack of Cytotoxicity of the Colorant in Conjugated Linoleic Acid against Human Cancer and Normal Cells

“…These results suggest that the color or colorant in the CLA samples did not have any effects on the proliferation of human cancer and normal cells and imply that the colorant in commercially available CLA samples is safe for human consumption. [2,3,6,8,9,11,14,21,23,24]. 또한 CLA는 항암효과 외 에 면역증진효과, 혈중 cholesterol 감소효과, 체지방감소효과 등 인체에 도움이 되는 기능성 물질임이 많은 연구자들에 의 해 밝혀졌다 [1,4,7,20] …”