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

• Published in: Toxicological research (Seoul) Vol. 35; no. 1; pp. 93 - 101
• Main Authors: Lee, Gi Ho, Jin, Sun Woo, Kim, Se Jong, Pham, Thi Hoa, Choi, Jae Ho, Jeong, Hye Gwang
• Format: Journal Article
• Language: English
• Published: Singapore 한국독성학회 01.01.2019; Springer Singapore; Korean Society of Toxicology
• Subjects: Biomedicine; Original; Original Article; Pharmacology/Toxicology; 예방의학; Akt; MAPK; MMP-9; Tetrabromobisphenol A; ROS
• ISSN: 1976-8257; 2234-2753
• DOI: 10.5487/TR.2019.35.1.093

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.