Chronic exposure of human glioblastoma tumors to low concentrations of a pesticide mixture induced multidrug resistance against chemotherapy agents

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dc.authoridKurtdere, Kardelen/0000-0002-4611-3436
dc.authoridDoganlar, Zeynep Banu/0000-0002-1365-9897
dc.authorwosidDoğanlar, Oğuzhan/A-2315-2019
dc.authorwosidKurtdere, Kardelen/KEE-9234-2024
dc.authorwosidDoganlar, Zeynep Banu/B-4845-2008
dc.contributor.authorDoganlar, Oguzhan
dc.contributor.authorDoganlar, Zeynep Banu
dc.contributor.authorKurtdere, Ayse Kardelen
dc.contributor.authorChasan, Tourkian
dc.contributor.authorOk, Esma Seben
dc.date.accessioned2024-06-12T11:12:18Z
dc.date.available2024-06-12T11:12:18Z
dc.date.issued2020
dc.departmentTrakya Üniversitesien_US
dc.description.abstractRecent evidence indicates that chronic, low-dose exposure to mixtures of pesticides can cause adverse responses in a variety of cells, tissues and organs, although interactions between pesticides circulating in the blood and cancer cells remain largely unexplored. The aim of this study was to investigate the potential of a mixture of four pesticides to induce multidrug resistance against the chemotherapeutic agents cisplatin, 5-fluorouracil and temozolomide in the human U87 glioblastoma cell line, and to explore the molecular mechanisms underlying this resistance. We found that the repeated administration of the pesticide mixture (containing the insecticides chlorpyrifos-ethyl and deltamethrin, the fungicide metiram, and the herbicide glyphosate) induced a strong drug resistance in U87 cells. The resistance was durable and transferred to subsequent cell generations. In addition, we detected a significant over-expression of the ATP-binding cassette (ABC) membrane transporters P-gp/ABCB1 and BRCP/ABCG2 as well as a glutathione-S-transferase (GST)/M1-type cellular detoxification function, known to have important roles in multidrug resistance, thus providing molecular support for the acquired multidrug resistance phenotype and shedding light on the mechanism of resistance. We further determined that there was lower mortality in the resistant brain tumor cells and that the mitochondrial apoptosis pathway was activated at a lower rate after chemotherapy compared to non-resistant control cells. In addition, multidrug-resistant cells were found to have both higher motility and wound-healing properties, suggesting a greater metastatic potential. Our results suggest that the investigation of P-gp, BRCP and GST/M1 multidrug resistance gene expression and/ or protein levels in biopsy specimens of brain tumor patients who were at risk of pesticide exposure could be beneficial in determining chemotherapy dose and prolonging patient survival.en_US
dc.description.sponsorshipTUBITAK (The Scientifc and Technological Research Council of Turkey) [217Z268]en_US
dc.description.sponsorshipThis work was supported by the TUBITAK (The Scientifc and Technological Research Council of Turkey; Project Number: 217Z268). The authors also thank Daryl Henderson for valuable comments and English editing.en_US
dc.identifier.doi10.1016/j.ecoenv.2020.110940
dc.identifier.issn0147-6513
dc.identifier.issn1090-2414
dc.identifier.pmid32800223en_US
dc.identifier.scopus2-s2.0-85087680888en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1016/j.ecoenv.2020.110940
dc.identifier.urihttps://hdl.handle.net/20.500.14551/23116
dc.identifier.volume202en_US
dc.identifier.wosWOS:000564335100015en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherAcademic Press Inc Elsevier Scienceen_US
dc.relation.ispartofEcotoxicology And Environmental Safetyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectPesticide Mixtureen_US
dc.subjectMultidrug Resistanceen_US
dc.subjectChemotherapyen_US
dc.subjectGlioblastoma Multiformeen_US
dc.subjectU87en_US
dc.subjectP-Glycoproteinen_US
dc.subjectAbc-Transportersen_US
dc.subjectDrug-Resistanceen_US
dc.subjectGlutathione Transferasesen_US
dc.subjectInsecticide Resistanceen_US
dc.subjectAgricultural-Workersen_US
dc.subjectSignaling Pathwaysen_US
dc.subjectConyza-Canadensisen_US
dc.subjectBlood-Serumen_US
dc.subjectCanceren_US
dc.titleChronic exposure of human glioblastoma tumors to low concentrations of a pesticide mixture induced multidrug resistance against chemotherapy agentsen_US
dc.typeArticleen_US

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