Tetrabromobisphenol A Induces MMP-9 Expression via NADPH Oxidase and the activation of ROS, MAPK, and Akt Pathways in Human Breast Cancer MCF-7 Cells
Toxicological Research 2019;35:93−101
Published online January 15, 2019;  https://doi.org/10.5487/TR.2019.35.1.093
© 2019 Korean Society of Toxicology.

Gi Ho Lee, Sun Woo Jin, Se Jong Kim, Thi Hoa Pham, Jae Ho Choi and Hye Gwang Jeong

Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon, Korea
Hye Gwang Jeong, Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon 34134, Korea, E-mail: hgjeong@cnu.ac.kr
The first two authors contributed equally to this work.
Received: October 31, 2018; Revised: November 6, 2018; Accepted: November 6, 2018
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Tetrabromobisphenol A (TBBPA), the most common industrial brominated flame retardant, acts as a cytotoxic, neurotoxic, and immunotoxicant, causing inflammation and tumors. However, the mechanism of TBBPA-induced matrix metalloproteinase-9 (MMP-9) expression in human breast cancer cells is not clear. In human breast cancer MCF-7 cells, treatment with TBBPA significantly induced the expression and promoter activity of MMP-9. Transient transfection with MMP-9 mutation promoter constructs verified that NF-κB and AP-1 response elements are responsible for the effects of TBBPA. Furthermore, TBBPA-induced MMP-9 expression was mediated by NF-κB and AP-1 transcription activation as a result of the phosphorylation of the Akt and MAPK signaling pathways. Moreover, TBBPA-induced activation of Akt/MAPK pathways and MMP-9 expression were attenuated by a specific NADPH oxidase inhibitor, and the ROS scavenger. These results suggest that TBBPA can induce cancer cell metastasis by releasing MMP-9 via ROS-dependent MAPK, and Akt pathways in MCF-7 cells.
Keywords : Tetrabromobisphenol A, MMP-9, ROS, MAPK, Akt


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