Glyphosate-induced glioblastoma cell proliferation: Unraveling the interplay of oxidative, inflammatory, proliferative, and survival signaling pathways.

Autor: Bianco CD; Department of Biochemistry, Center of Biological Sciences, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil., Ourique F; Department of Biochemistry, Center of Biological Sciences, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil., Dos Santos DC; Department of Biochemistry, Center of Biological Sciences, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil., Pedrosa RC; Department of Biochemistry, Center of Biological Sciences, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil., Kviecisnki MR; Department of Biochemistry, Center of Biological Sciences, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil., Zamoner A; Department of Biochemistry, Center of Biological Sciences, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil. Electronic address: ariane.zamoner@ufsc.br.
Jazyk: angličtina
Zdroj: Environmental pollution (Barking, Essex : 1987) [Environ Pollut] 2023 Dec 01; Vol. 338, pp. 122695. Date of Electronic Publication: 2023 Oct 04.
DOI: 10.1016/j.envpol.2023.122695
Abstrakt: 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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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