Division of Applied Life Science (BK21 Program), Graduate School, and Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 660-701, Republic of Korea.
J Agric Food Chem. 2010 Nov 24;58(22):12022-30. doi: 10.1021/jf103205c. Epub 2010 Oct 28.
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.
c9,t11-共轭亚油酸（CLA）对 12-O-十四烷酰佛波醇-13-乙酸酯（TPA）处理的人乳腺上皮细胞系（MCF-10A）中缝隙连接细胞间通讯（GJIC）抑制的保护作用与 t10,c12-CLA 异构体进行了研究。TPA 以剂量依赖和可逆的方式抑制 GJIC，并与连接蛋白 43 磷酸化有关。在 60 nM TPA 处理 1 h 之前，用 20 μM c9,t11-CLA 预处理 24 h 可通过抑制细胞外信号调节激酶（ERK1/2）的激活来减少连接蛋白 43 的磷酸化，从而防止 GJIC 的抑制。c9,t11-CLA 减弱了 TPA 引起的活性氧（ROS）积聚。c9,t11-CLA 保护 GJIC 抑制、连接蛋白 43 磷酸化和 ROS 产生的功效优于 t10,c12-CLA。这些结果表明，c9,t11-CLA（包括 t10,c12-CLA）通过在癌症促进阶段保护 GJIC 的下调来预防 MCF-10A 细胞的癌变，并且缺乏它们的毒性可能是乳腺癌化学预防的一个极好指标。
