Metabolic perturbation, proliferation and reactive oxygen species jointly contribute to cytotoxicity of human breast cancer cell induced by tetrabromo and tetrachloro bisphenol A.

Abstract

Halogenated bisphenol A analogues (X-BPA) have been widely used in industrial production, such as flame retardant. Although BPA exposure was found to result in cytotoxicity, toxicity of X-BPA and molecular mechanism remain under-explored. In this study, we employed human breast cancer cell as a model to investigate the concentration-dependent toxicity and underlying mechanisms of tetrabromo bisphenol A (TBBPA) and tetrachloro bisphenol A (TCBPA). An integrated method involving molecular toxicology and mass spectrometry (MS)-based global metabolomics was applied to evaluate the toxicity of TCBPA and TBBPA on cell viability, reactive oxygen species (ROS), and metabolic alterations. The results demonstrated that low micromolar levels (0-10 μM) of TCBPA/TBBPA exposure induced cell proliferation and activated the energy metabolism of both glycolysis and amino acid. On the other hand, high micromolar levels (10-50 μM) of TCBPA/TBBPA exposure perturbed the balance between ROS and antioxidative defense process by promoting the ROS generation via the down-regulation of glutathione biosynthesis and up-regulation of nucleotide metabolism. This study, for the first time, provides evidence and mechanism for better understanding the cytotoxicity of TCBPA and TBBPA by regulating the specific metabolic pathways.

• Authors: Chao Zhao, Zhi Tang, Arthur Chi Kong Chung, Hailin Wang, Zongwei Cai
• Journal: Ecotoxicology and environmental safety (Ecotoxicol Environ Saf) Vol. 170 Pg. 495-501 (Apr 15 2019) ISSN: 1090-2414 [Electronic] Netherlands
• PMID: 30557707 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• Benzhydryl Compounds
• Chlorophenols
• Flame Retardants
• Phenols
• Polybrominated Biphenyls
• Reactive Oxygen Species
• tetrachlorodian
• tetrabromobisphenol A
• bisphenol A

Topics

• Benzhydryl Compounds (toxicity)
• Breast Neoplasms
• Cell Line, Tumor
• Cell Proliferation
• Cell Survival (drug effects)
• Chlorophenols (toxicity)
• Dose-Response Relationship, Drug
• Flame Retardants (toxicity)
• Humans
• Metabolic Networks and Pathways (drug effects, genetics)
• Oxidative Stress (drug effects)
• Phenols (toxicity)
• Polybrominated Biphenyls (toxicity)
• Reactive Oxygen Species (metabolism)