2. Academic Validation
  3. Effects of the emerging contaminant 1,3,6,8-tetrabromocarbazole on the NF-κB and correlated mechanism in human hepatocellular carcinoma cells

Effects of the emerging contaminant 1,3,6,8-tetrabromocarbazole on the NF-κB and correlated mechanism in human hepatocellular carcinoma cells

  • Ecotoxicol Environ Saf. 2022 Oct 21;247:114199. doi: 10.1016/j.ecoenv.2022.114199.
Tong Xu 1,  Yu Jiang 2,  Xiaoxu Hu 1,  Guanglei Yang 1,  Yangsheng Chen 1,  Songyan Zhang 3,  Qian Zhang 4,  Liping Zheng 1,  Heidi Qunhui Xie 1,  Li Xu 5,  Bin Zhao 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  • 2 Department of Preventive Medicine, Fujian Provincial Key Laboratory of Environment Factors and Cancer, Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350122, China.
  • 3 Engineering Laboratory of Shenzhen Natural Small Molecule Innovative Drugs, Health Science Center, Shenzhen University, Shenzhen 518060, China.
  • 4 Department of Cardiology, Beijing Hospital, National Center of Gerontology, Beijing 100730, China.
  • 5 State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: [email protected].
  • 6 State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China; School of environment, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China.
PMID: 36274317 DOI: 10.1016/j.ecoenv.2022.114199
Abstract

1,3,6,8-Tetrabromocarbazole (1368-BCZ) is identified as an emerging contaminant that exerts angiogenic effects. Multiple studies indicated there was a positive correlation between angiogenesis and nuclear factor kappa B (NF-κB) activation. While the role of NF-κB in inflammation and Apoptosis has been well known, the potential biological effects of 1368-BCZ on NF-κB signaling and related mechanism remain unclear. We, therefore, explored the possible effects of 1368-BCZ on the NF-κB pathway at the gene and protein levels and confirmed that NF-κB activation by 1368-BCZ exposure caused an augmented phosphorylated protein level, induction of NF-κB response element (κBRE)-driven luciferase activity and upregulation of transcriptional level of downstream responsive genes. Although 1368-BCZ did not produce detectable changes in hepatic fibrosis in vivo, it obviously altered the Apoptosis in human hepatocellular carcinoma (HepG2) cells. Furthermore, the induction of Apoptosis was confirmed by the increased cleaved Caspase-3 level. These data revealed the activating effects of 1368-BCZ on NF-κB and its involvement in the underlying mechanisms, providing additional information for toxicology studies of emerging contaminants and introducing a mechanism-based toxicological evaluation of emerging pollutants.

Keywords

1,3,6,8-Tetrabromocarbazole; Apoptosis; HepG2 cells; NF-κB.

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