Activation of G protein-coupled receptor 30 by thiodiphenol promotes proliferation of estrogen receptor α-positive breast cancer cells. (February 2017)

• Record Type: Journal Article
• Authors: Lei, Bingli; Peng, Wei; Xu, Gang; Wu, Minghong; Wen, Yu; Xu, Jie; Yu, Zhiqiang; Wang, Yipei
• Is Part Of: Chemosphere. Volume 169(2017)
• Page Start: 204
• Page End: 211
• Publication Date: 2017-02
• Subjects: TDP -- MCF-7 cells -- Biological effect -- Estrogen receptor -- Molecular mechanism; Pollution -- Periodicals; Pollution -- Physiological effect -- Periodicals; Environmental sciences -- Periodicals; Atmospheric chemistry -- Periodicals; 551.511
• DOI: 10.1016/j.chemosphere.2016.11.066
• Languages: English
• ISSNs: 0045-6535

Abstract

Abstract: Many studies have been shown that environmental estrogen bisphenol A (BPA) can activate nuclear receptor (estrogen receptor alpha, ERα) or membrane receptor (G-protein-coupled receptor, GPR30) in breast cancer cells and exerts genomic or nongenomic actions inducing cell proliferation. 4, 4′-thiodiphenol (TDP) as one of BPA derivatives exhibits more potent estrogenic activity than BPA does. However, comparatively little is known about the ways in which TDP interferes with these signaling pathways and produces cell biological changes. This study evaluated the effect of TDP on cell viability, reactive oxygen species (ROS) formation, and intercellular calcium (Ca 2+ ) fluctuation in MCF-7 breast cancer cells. The underlying molecular mechanism of cell proliferation induced by TDP was analyzed by examining the activation of ERα and GPR30-mediated phosphatidylinotidol 3-kinase/protein kinase B (PI3K/AKT) and extracellular-signa1regulated kinase (ERK1/2) signaling pathways. The results showed that exposure to 0.1–10 μM TDP for 24, 48, and 72 h significantly increased viability of MCF-7 cells. At the same concentration range, TDP exposure for 3 and 24 h markedly elevated ROS production and intracellular Ca 2+ levels. In addition, 0.01–1 μM TDP significantly increased the expression of ERα, GPR30, p-AKT and p-ERK1/2 protein. Specific protein inhibitors blocked phosphorylation of ERK1/2 and AKT and decreased TDP-induced cell proliferation. These findings show that TDP activated the GPR30-PI3K/AKT and ERK1/2 pathways, and the resulting interaction with ERα stimulated MCF-7 cell proliferation. Our results indicate a novel mechanism through which TDP may exert relevant estrogenic action in ERα positive cancer cells. Highlights: Low doses of TDP increased cell viability, intracellular Ca 2+ and ROS levels. TDP activated the PI3K/AKT and ERK signaling pathways via GPR30. GPR30 mediated the TDP-induced cell proliferation. ERα plays important role in TDP-induced cell proliferation effect. TDP elicits estrogenic action via cross talk between ERα and GPR30 pathways.