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

Abstract

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.

Misexpression of Wingless-Related MMTV Integration Site 5A in Mouse Mammary Gland Inhibits the Milk Ejection Response and Regulates Connexin43 Phosphorylation1

“…MCF10A cells are a nontumorigenic breast epithelial cell line that was previously shown to be competent for gap junction intercellular communication (GJIC) [23,24]. The primary function of Cx43 is to mediate GJIC, a direct connection of the cytoplasm of two cells that allows various molecules to pass between the cells.…”

“…To determine if ectopic WNT5A and the changes seen in Cx43 phosphorylation correlated to any alteration in Cx43 function, we performed a dye transfer assay using MCF10A cells [18,23,24]. MCF10A cells are a nontumorigenic breast epithelial cell line that was previously shown to be competent for gap junction intercellular communication (GJIC) [23,24].…”

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

“…GJIC has been postulated to regulate cell proliferation, differentiation, apoptosis, and adaptive responses of differentiated cells [11, 12]. Tumor promoters downregulate GJIC in carcinogenesis [13, 14], and GJIC is suppressed in most cancer cells compared to normal cells [15, 16]. In addition, growth factors and several oncogenes inhibit GJIC [17], and cancer drugs reverse downregulation of GJIC [18–21].…”

Method for Screening of Bacterial Strains Biosynthesizing Specific Conjugated Linoleic Acid Isomers

“…1−3 Recently, more and more studies showed that each CLA isomer has unique bioactive properties. cis9,trans11-CLA has the anticarcinogenic biological activity in Caco-2 and MCF-10A cells, 4,5 whereas trans10,cis12-CLA appears to be specifically responsible for enhancement of energy metabolism in Chang liver cells and reducing liver lipid content in Zucker rats. 6,7 CLA occurs naturally in fat of dairy products and meat from ruminant animals at a level lower than 10 mg/g of fat usually.…”