Fenpyroximate（FEN）是一种螨虫酰胺类杀虫剂，可以抑制线粒体电子传递中的NADH-辅酶Q氧化酶还原酶（复合物I）。本研究旨在研究FEN对培养的人结肠癌细胞（HCT116）毒性的分子机制。我们的数据表明，FEN以浓度依赖方式导致HCT116细胞死亡。FEN阻滞了细胞周期在G0/G1期，并通过彗星实验评估增加了DNA损伤。通过AO-EB染色和Annexin V-FITC/PI双染色实验证实了FEN引起的HCT116细胞凋亡诱导。此外，FEN导致线粒体膜电位（MMP）的下降，增加了p53和Bax mRNA表达，并降低了bcl2 mRNA水平。还检测到了caspase 9和caspase 3活性的增加。总之，这些数据表明FEN通过线粒体途径引起HCT116细胞凋亡。为了检查氧化应激在FEN诱导的细胞毒性中的作用，我们检查了FEN暴露的HCT116细胞中的氧化应激状态，并测试了一种强效抗氧化剂N-乙酰半胱氨酸（NAC）对FEN造成的毒性的影响。观察到FEN增强了ROS产生和MDA水平，并扰乱了SOD和CAT的活性。此外，细胞用NAC处理显著保护了细胞免受FEN引起的死亡、DNA损伤、MMP损失和caspase 3活性的影响。据我们所知，这是首个显示FEN通过ROS产生和氧化应激诱导线粒体凋亡的研究。版权所有©2023 Elsevier Ltd.

Fenpyroximate (FEN) is an acaricide that inhibits mitochondrial electron transport at the NADH-coenzyme Q oxidoreductase (complex I). The present study was designed to investigate the molecular mechanisms underling FEN toxicity on cultured human colon carcinoma cells (HCT116). Our data showed that FEN induced HCT116 cell mortality in a concentration dependent manner. FEN arrested cell cycle in G0/G1 phase and increased DNA damage as assessed by comet assay. Induction of apoptosis was confirmed in HCT116 cells exposed to FEN by AO-EB staining and Annexin V-FITC/PI double staining assay. Moreover, FEN induced a loss in mitochondrial membrane potential (MMP), increased p53 and Bax mRNA expression and decreased bcl2 mRNA level. An increase in caspase 9 and caspase 3 activities was also detected. All toghether, these data suggest that FEN induce apoptosis in HCT116 cells via mitochondrial pathway. To check the implication of oxidative stress in FEN-induced cell toxicity, we examined the oxidative stress statue in HCT116 cells exposed to FEN and we tested the effect of a powerful antioxidant, N-acetylcystein (NAC), on FEN-caused toxicity. It was observed that FEN enhanced ROS generation and MDA levels and disturbed SOD and CAT activities. Besides, cell treatment with NAC significantly protected cells from mortality, DNA damage, loss of MMP, and caspase 3 activity induced by FEN. To the best of our knowledge, this is the first study showing that FEN induced mitochondrial apoptosis via ROS generation and oxidative stress.Copyright © 2023. Published by Elsevier Ltd.