Polychlorinated Biphenyl Quinones Promotes Breast Cancer Metastasis through Reactive Oxygen Species-Mediated Nuclear Factor κB-Matrix Metalloproteinase Signaling.

Abstract

It is generally acknowledged that polychlorinated biphenyls (PCBs) exposure increased the incidence of cancer, however, the underlying mechanism(s) of PCBs-induced cancer metastasis are unclear. Although PCBs readily metabolize, little information is available regarding the effect of PCBs metabolites on cancer metastasis. Currently, we evaluate a highly reactive PCBs metabolite, 2,3,5-trichloro-6-phenyl-[1,4]-benzoquinone (PCB29-pQ), relevant to exposure with mammary cancer metastasis. Multiple lines of evidence illustrated that PCB29-pQ induces breast cancer invasion and migration. In particular, this appearance is associated with a two-fold elevation of matrix metalloproteinases-2/-9 (MMP-2/-9) and extracellular nuclear factor kappa B (NF-κB), respectively. Our results clearly demonstrated the translocation of cytosolic NF-κB into the nucleus by a factor of about 2.4. We also revealed the activation of corresponding upstream signaling cascades phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt and p38 and extracellular regulated protein kinases (ERK) mitogen-activated protein kinase (MAPK) by factors of 3.15, 3.09 and 1.69, respectively. Moreover, there was a marked induction of reactive oxygen species (ROS) after a PCB29-pQ challenge and antioxidant treatment that markedly inhibited PCB29-pQ-mediated activation of these axis signaling. Collectively, our result suggested that PCB29-pQ induces breast cancer metastasis via ROS-dependent NF-κB-MMP signaling.