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KMID : 0379520190350010093
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한국독성학회지
2019 Volume.35 No. 1 p.93 ~ p.101
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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
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Lee Gi-Ho
Jin Sun-Woo
Kim Se-Jong
Pham Thi Hoa
Choi Jae-Ho
Jeong Hye-Gwang
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Abstract
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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.
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KEYWORD
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Tetrabromobisphenol A, MMP-9, ROS, MAPK, Akt
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