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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

  • Lee, Gi Ho (Department of Toxicology, College of Pharmacy, Chungnam National University) ;
  • Jin, Sun Woo (Department of Toxicology, College of Pharmacy, Chungnam National University) ;
  • Kim, Se Jong (Department of Toxicology, College of Pharmacy, Chungnam National University) ;
  • Pham, Thi Hoa (Department of Toxicology, College of Pharmacy, Chungnam National University) ;
  • Choi, Jae Ho (Department of Toxicology, College of Pharmacy, Chungnam National University) ;
  • Jeong, Hye Gwang (Department of Toxicology, College of Pharmacy, Chungnam National University)
  • Received : 2018.10.31
  • Accepted : 2018.11.06
  • Published : 2019.01.15

Abstract

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 $NF-{\kappa}B$ and AP-1 response elements are responsible for the effects of TBBPA. Furthermore, TBBPA-induced MMP-9 expression was mediated by $NF-{\kappa}B$ 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

References

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