Department of Biochemistry, Center of Biological Sciences, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.
Department of Biochemistry, Center of Biological Sciences, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.
Environ Pollut. 2023 Dec 1;338:122695. doi: 10.1016/j.envpol.2023.122695. Epub 2023 Oct 4.
The aim of the present study was to investigate the impacts of glyphosate herbicide on the survival and proliferation of glioblastoma cells and to explore the molecular mechanisms underlying such effects. For this, cultured human glioblastoma cell line, A172, was exposed to the glyphosate analytical standard, a glyphosate-based herbicide formulation (GBH), or the metabolite aminomethylphosphonic acid (AMPA). The three compounds induced A172 cytotoxicity after 24 h of exposure, with more prominent cytotoxic effects after 48 and 72 h of treatment. Further experiments were performed by treating A172 cells for 6 h with glyphosate, GBH, or AMPA at 0.5 mg/L, which corresponds to the maximum residue limits for glyphosate and AMPA in drinking water in Brazil. Colony forming units (CFU) assay showed that AMPA increased the number of CFU formed, while glyphosate and GBH increased the CFU sizes. The three compounds tested altered the cell cycle and caused DNA damage, as indicated by the increase in γ-H2AX. The mechanisms underlying the pesticide effects involve the activation of Akt and mitogen-activated protein kinases (MAPKs) signaling pathways, oxidative imbalance, and inflammation. Glyphosate led to NLRP3 activation culminating in caspase-1 recruitment, while AMPA decreased NLRP3 immunocontent and GBH did not alter this pathway. Results of the present study suggest that exposure to glyphosate (isolated or in formulation) or to its metabolite AMPA may affect cell signaling pathways resulting in oxidative damage and inflammation, giving glioblastoma cells an advantage by increasing their proliferation and growth.
本研究旨在探究草甘膦除草剂对神经胶质瘤细胞存活和增殖的影响，并探讨其作用的分子机制。为此，我们将培养的人神经胶质瘤细胞系 A172 暴露于草甘膦分析标准品、草甘膦制剂（GBH）或代谢物氨甲基膦酸（AMPA）中。三种化合物在暴露 24 小时后诱导 A172 细胞产生细胞毒性，在处理 48 和 72 小时后产生更显著的细胞毒性作用。进一步的实验是用 0.5mg/L 的草甘膦、GBH 或 AMPA 处理 A172 细胞 6 小时完成的，这相当于巴西饮用水中草甘膦和 AMPA 的最大残留限量。集落形成单位（CFU）实验表明，AMPA 增加了 CFU 的形成数量，而草甘膦和 GBH 增加了 CFU 的大小。三种测试化合物改变了细胞周期并导致 DNA 损伤，这表现为 γ-H2AX 的增加。农药作用的机制涉及 Akt 和丝裂原活化蛋白激酶（MAPKs）信号通路的激活、氧化失衡和炎症。草甘膦导致 NLRP3 激活，最终导致 caspase-1 募集，而 AMPA 降低 NLRP3 免疫含量，GBH 则没有改变该途径。本研究结果表明，暴露于草甘膦（单独或在制剂中）或其代谢物 AMPA 可能会影响细胞信号通路，导致氧化损伤和炎症，从而通过增加神经胶质瘤细胞的增殖和生长为其提供优势。
