Bromuconazole fungicide induces cell cycle arrest and apoptotic cell death in cultured human colon carcinoma cells (HCT116) via oxidative stress process. (14th October 2022)

• Record Type: Journal Article
• Authors: Rjiba-Touati, Karima; Ayed-Boussema, Imen; Hamdi, Hiba; Azzebi, Awatef; Abid, Salwa
• Is Part Of: Biomarkers. Volume 27:Number 7(2022)
• Page Start: 659
• Page End: 670
• Publication Date: 2022-10-14
• Subjects: Bromuconazole -- HCT116 cells -- cell cycle arrest -- DNA damage -- caspase-3 -- annexin V FITC-PI staining -- apoptosis -- oxidative stress; Biochemical markers -- Periodicals; 610.28
• DOI: 10.1080/1354750X.2022.2098378
• Languages: English
• ISSNs: 1354-750X

Abstract

Abstract: Background: Bromuconazole, a fungicide belonging to the triazole family, is a plant protection product used to control, repel or destroy fungi that may develop on crops. We investigated the pro-apoptotic effect of bromuconazole and the role of oxidative stress in the death mechanism induced by this fungicide in this study. Methods: The human colon HCT116 cell line was treated with Bromuconazole (IC50/4, IC50/2, and IC50) for 24 h. Cells were collected and analysed for biomarkers of apoptotic cell death and oxidative stress as well as for the assessment of genotoxic damage. Results: Our study showed that bromuconazole caused a concentration-dependent increase in cell mortality with an IC50 of 180 µM. Bromuconazole induced cell cycle arrest in the G0/G1 phase and DNA synthesis inhibition. The Comet assay showed that bromuconazole caused DNA damage in a concentration-dependent manner. Bromuconazole-induced apoptosis was observed by, Annexin-V/FITC-PI and BET/AO staining, by mitochondrial membrane depolarisation, and by increased caspase-3 activity. In addition, bromuconazole induced a significant increase in ROS and lipid peroxidation levels and a disruption in SOD and CAT activities. N-acetylcysteine (NAC) strongly prevents cytotoxic and genotoxic damage caused by bromuconazole. Conclusion: Bromuconazole toxicity was through the oxidative stress process, which causes DNA damage and mitochondrial dysfunction, leading to cell cycle arrest and apoptotic death of HCT116 cells. Highlights: Bromuconazole exposure induced cell cycle arrest in the G0/G1 in HCT116 cells. Bromuconazole caused DNA synthesis inhibition and degradation. Bromuconazole-induced Annexin-V/FITC-PI and BET/AO positive staining, increased caspase-3 activity and MMP. Bromuconazole enhances ROS, MDA levels and disruption of CAT and SOD activities.