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.