Triclosan induces pyroptosis by activation of the caspase-9/3/gasdermin E axis

The high concentrations of TCS in personal care products, and the potential for even greater exposure in occupational settings, raise significant concerns about its cytotoxic effects. Numorous studies highlight the importance of understanding the molecular mechanisms of pyroptosis in toxicological r...

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Main Authors: Shiqi Wu, Lei You, Shan He, Wenqaing Liu, Jinlin Lei, Jiahui Yang, Xiangyin Luo, Zhenxiu Ye, Yonghong Zhang, Jing Wang, Huailan Guo, Yan Zheng, Lanlan Zheng, Chen Li
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2025-03-01
Series:Emerging Contaminants
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Online Access:http://www.sciencedirect.com/science/article/pii/S2405665024001264
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Summary:The high concentrations of TCS in personal care products, and the potential for even greater exposure in occupational settings, raise significant concerns about its cytotoxic effects. Numorous studies highlight the importance of understanding the molecular mechanisms of pyroptosis in toxicological research on environmental pollutants. However, it remains unclear whether TCS exposure could induce GSDME-mediated pyroptosis. In this study, we aimed to investigate the cytotoxic effects of 200 μM TCS on L02 cells and elucidate the molecular mechanisms involved in TCS-induced pyroptosis, a novel form of cell death. Our results demonstrate that TCS inhibits the proliferation of L02 cells in a dose-dependent manner and triggers caspase-dependent cell death, leading to mitochondrial dysfunction and subsequent pyroptosis through the activation of the caspase-9/3/GSDME axis. Furthermore, through transcriptional and metabolomic analyses, we identified alterations in the PI3K-Akt and MAPK cellular signaling pathways, as well as changes in carbon and nitrogen metabolism. Our data provide valuable insights into the biotoxicity of high TCS concentrations and establish a theoretical basis for future studies on its impact and risk.
ISSN:2405-6650