PMID- 30080411 OWN - NLM STAT- MEDLINE DCOM- 20190729 LR - 20190729 IS - 1520-5010 (Electronic) IS - 0893-228X (Linking) VI - 31 IP - 9 DP - 2018 Sep 17 TI - Polychlorinated Biphenyl Quinones Promotes Breast Cancer Metastasis through Reactive Oxygen Species-Mediated Nuclear Factor kappaB-Matrix Metalloproteinase Signaling. PG - 954-963 LID - 10.1021/acs.chemrestox.8b00148 [doi] AB - 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-kappaB), respectively. Our results clearly demonstrated the translocation of cytosolic NF-kappaB 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-kappaB-MMP signaling. FAU - Wang, Yuxin AU - Wang Y AD - Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences , Southwest University , Chongqing , People's Republic of China , 400715. FAU - Wang, Yawen AU - Wang Y AD - Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences , Southwest University , Chongqing , People's Republic of China , 400715. FAU - Liu, Zixuan AU - Liu Z AD - Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences , Southwest University , Chongqing , People's Republic of China , 400715. FAU - Dong, Wenjing AU - Dong W AD - Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences , Southwest University , Chongqing , People's Republic of China , 400715. FAU - Yang, Bingwei AU - Yang B AD - Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences , Southwest University , Chongqing , People's Republic of China , 400715. FAU - Xia, Xiaomin AU - Xia X AD - Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences , Southwest University , Chongqing , People's Republic of China , 400715. FAU - Song, Erqun AU - Song E AUID- ORCID: 0000-0003-4026-090X AD - Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences , Southwest University , Chongqing , People's Republic of China , 400715. FAU - Song, Yang AU - Song Y AUID- ORCID: 0000-0001-7716-9216 AD - Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences , Southwest University , Chongqing , People's Republic of China , 400715. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180821 PL - United States TA - Chem Res Toxicol JT - Chemical research in toxicology JID - 8807448 RN - 0 (2,3,5-trichloro-6-phenyl-(1,4)benzoquinone) RN - 0 (Benzoquinones) RN - 0 (NF-kappa B) RN - 0 (Reactive Oxygen Species) RN - DFC2HB4I0K (Polychlorinated Biphenyls) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 3.4.24.24 (MMP2 protein, human) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) RN - EC 3.4.24.35 (MMP9 protein, human) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) MH - Animals MH - Benzoquinones/chemistry/*toxicity MH - Breast Neoplasms/enzymology/*metabolism/*pathology MH - Cell Line, Tumor MH - Enzyme Induction MH - Female MH - Heterografts MH - Humans MH - Matrix Metalloproteinase 2/biosynthesis/*metabolism MH - Matrix Metalloproteinase 9/biosynthesis/*metabolism MH - Mice MH - Mice, Inbred BALB C MH - Mice, Nude MH - Mitogen-Activated Protein Kinases/metabolism MH - NF-kappa B/*metabolism MH - Neoplasm Invasiveness MH - *Neoplasm Metastasis MH - Phosphatidylinositol 3-Kinases/metabolism MH - Polychlorinated Biphenyls/chemistry/*toxicity MH - Proto-Oncogene Proteins c-akt/metabolism MH - Reactive Oxygen Species/*metabolism EDAT- 2018/08/07 06:00 MHDA- 2019/07/30 06:00 CRDT- 2018/08/07 06:00 PHST- 2018/08/07 06:00 [pubmed] PHST- 2019/07/30 06:00 [medline] PHST- 2018/08/07 06:00 [entrez] AID - 10.1021/acs.chemrestox.8b00148 [doi] PST - ppublish SO - Chem Res Toxicol. 2018 Sep 17;31(9):954-963. doi: 10.1021/acs.chemrestox.8b00148. Epub 2018 Aug 21.