Ayed-Boussema Imen, Rjiba-Touati Karima, Hamdi Hiba, Chaabani Hanen, Abid-Essefi Salwa
Laboratory of Research on Biologically Compatible Compounds, LR01SE17 University of Monastir, Faculty of Dental Medicine, 5019 Monastir, Tunisia; Faculty of Sciences of Gafsa, University of Gafsa, Tunisia.
Laboratory of Research on Biologically Compatible Compounds, LR01SE17 University of Monastir, Faculty of Dental Medicine, 5019 Monastir, Tunisia; Faculty of Sciences of Gafsa, University of Gafsa, Tunisia.
Toxicol In Vitro. 2023 Jun;89:105587. doi: 10.1016/j.tiv.2023.105587. Epub 2023 Mar 17.
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.
唑螨酯（FEN）是一种杀螨剂，可抑制线粒体电子传递链中的NADH-辅酶Q氧化还原酶（复合体I）。本研究旨在探讨唑螨酯对培养的人结肠癌细胞（HCT116）产生毒性作用的分子机制。我们的数据表明，唑螨酯以浓度依赖的方式诱导HCT116细胞死亡。唑螨酯使细胞周期停滞在G0/G1期，并通过彗星试验评估发现其增加了DNA损伤。通过AO-EB染色和Annexin V-FITC/PI双染法证实，暴露于唑螨酯的HCT116细胞发生了凋亡。此外，唑螨酯导致线粒体膜电位（MMP）丧失，增加了p53和Bax mRNA表达，并降低了bcl2 mRNA水平。还检测到半胱天冬酶9和半胱天冬酶3活性增加。总之，这些数据表明唑螨酯通过线粒体途径诱导HCT116细胞凋亡。为了检验氧化应激在唑螨酯诱导的细胞毒性中的作用，我们检测了暴露于唑螨酯的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）对唑螨酯所致毒性的影响。结果发现，唑螨酯增强了ROS生成和MDA水平，并扰乱了SOD和CAT活性。此外，用NAC处理细胞可显著保护细胞免受唑螨酯诱导的死亡、DNA损伤、MMP丧失和半胱天冬酶3活性增加的影响。据我们所知，这是第一项表明唑螨酯通过ROS生成和氧化应激诱导线粒体凋亡的研究。
