Effects of Decabrominated Diphenyl Ether (PBDE-209) in Regulation of Growth and Apoptosis of Breast, Ovarian, and Cervical Cancer Cells

Abstract

Background: Polybrominated diphenyl ethers (PBDEs), commonly used in building materials, electronics, plastics, polyurethane foams, and textiles, are health hazards found in the environment.Objective: In this study we investigated the effects of PBDE-209, a deca-PBDE, on the regulation of growth and apoptosis of breast, ovarian, and cervical cancer cells as well as the underlying protein alterations.Methods: We used MCF-7 and MCF-7/ADR (multidrug-resistant MCF-7) breast cancer cell lines, the HeLa cervical cancer cell line, the OVCAR-3 ovarian cancer cell line, and the normal CHO (Chinese hamster ovary) cell line to assess the effects of PBDE-209 using cell viability, immunofluorescence, and flow cytometric assays. Western blot assays were used to detect changes in protein expression. To assess the effects of PBDE-209 on apoptosis, we used the protein kinase Cα (PKCα) inhibitor Gö 6976, the extracellular signal-regulated kinase (ERK) inhibitor PD98059, and tamoxifen.Results: Our data indicate that PBDE-209 increased viability and proliferation of the tumor cell lines and in CHO cells in a dose- and time-dependent manner. PBDE-209 also altered cell cycle distribution by inducing the S phase or G2/M phase. Furthermore, PBDE-209 partially suppressed tamoxifen-induced cell apoptosis in the breast cancer cell lines (MCF-7 and MCF-7/ADR) but suppressed Gö 6976- and PD98059-induced apoptosis in all cell lines. At the molecular level, PBDE-209 enhanced PKCα and ERK1/2 phosphorylation in the cell lines.Conclusions: Our data demonstrate that PBDE-209 is able to promote proliferation of various cancer cells from the female reproductive system and normal ovarian CHO cells. Furthermore, it reduced tamoxifen, PKCα, and ERK inhibition-induced apoptosis. Finally, PBDE-209 up-regulated phosphorylation of PKCα and ERK1/2 proteins in tumor cells and in CHO cells.

Extracellular NAMPT/Visfatin induces proliferation through ERK1/2 and AKT and inhibits apoptosis in breast cancer cells

“…They showed that phosphorylation of ERK1/2 is increased by IGF-1 and this increase is constantly high after 60 minutes. Similar pattern for ERK phosphorylation has been reported in response to some chemicals other than growth factors [45].…”

Protective effect of (±)α-tocopherol on brominated diphenyl ether-47-stimulated prostaglandin pathways in human extravillous trophoblasts in vitro

“…This may explain why COX expression is not entirely dependent on ROS formation in the present study. Although there are limited studies on PBDE effects on cellular signaling pathways, it is reported that a commercial PBDE mixture DE-71 and PBDE congeners such as BDE-47, 77, 99, and 209 stimulates PKC translocation, PKC phosphorylation, and ERK phosphorylation in vitro (Fan et al , 2010; Li et al , 2012; Madia et al , 2004). Further investigation on the interactions among kinase signaling pathways, transcription factors, and prostaglandin pathways will lead us toward a better understanding of the mechanisms associated with PGE2 production and COX expression stimulated by BDE-47 in gestational compartments.…”

In vitro immune toxicity of polybrominated diphenyl ethers on murine peritoneal macrophages: Apoptosis and immune cell dysfunction

“…nervous system (Dingemans et al, 2011), the liver, reproduction and development (Li et al, 2012) and the endocrine system Ren and Guo, 2012;Li et al, 2013;Ren and Guo, 2013). Although there is limited information on the immunotoxicity of PBDEs, recent animal investigations indicate suppressive effects of PBDEs on the immune system.…”