Prolonged sub-lethal exposure to galaxolide (HHCB) and tonalide (AHTN) promotes the metastatic potential of glioblastoma tumor spheroids

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dc.authoridDoganlar, Zeynep Banu/0000-0002-1365-9897
dc.authoridKurtdere, Kardelen/0000-0002-4611-3436
dc.authoridDoganlar, Oguzhan/0000-0003-2654-7269
dc.authorwosidDoganlar, Zeynep Banu/B-4845-2008
dc.authorwosidKurtdere, Kardelen/KEE-9234-2024
dc.contributor.authorDoganlar, Oguzhan
dc.contributor.authorDoganlar, Zeynep Banu
dc.contributor.authorChasan, Tourkian
dc.contributor.authorKurtdere, Ayse Kardelen
dc.date.accessioned2024-06-12T11:02:25Z
dc.date.available2024-06-12T11:02:25Z
dc.date.issued2021
dc.departmentTrakya Üniversitesien_US
dc.description.abstractGalaxolide and tonalide are well-known polycyclic musks whose intensive use without limitations in numerous cleaning, hygiene, and personal care products has resulted in widespread direct human exposure via absorption, inhalation, and oral ingestion. Latest data shows that long-term, low-dose exposure to toxic chemicals can induce unpredictable harmful effects in a variety of living systems, however, interactions between synthetic musks and brain tumours remain largely unexplored. Glioblastoma (GB) accounts for nearly half of all tumours of the central nervous system and is characterized by very poor prognosis. The aims of this study were (1) to investigate the potential effect of long-term (20-generation) single and combined application of galaxolide and tonalide at sub-lethal doses (5-2.5 u M) on the angiogenesis, invasion, and migration of human U87 cells or tumour spheroids, and (2) to explore the underlying molecular mechanisms. Random amplified polymorphic DNA assays revealed significant DNA damage and increased total mutation load in galaxolide- and/or tonalide-treated U87 cells. In those same groups, we also detected remarkable tumour spheroid invasion and up-regulation of both HIF1-alpha/VEGF/MMP9 and IL6/JAK2/STAT3 signals, known to have important roles in hypoxia-related angiogenesis and/or proliferation. Prolonged musk treatment further altered angio-miRNA expression in a manner consistent with poor prognosis in GB. We also detected significant over-expression of the genes Slug, Snail, ZEB1, and Vimentin, which are biomarkers of epithelial to mesenchymal transition. In addition, matrigel, transwell, and wound healing assays clearly showed that long-term sub-lethal exposure to galaxolide and/or tonalide induced invasion and migration proposing a high metastatic potential. Our results suggest that assessing expression of HIF-1a, VEGF, STAT3, and the miR-17-92 cluster in biopsy samples of GB patients who have a history of possible long-term exposure to galaxolide or tonalide could be beneficial for deciding a therapy regime. Additionally, we recommend that extensively-used hygiene and cleaning materials be selected from synthetic musk-free products, especially when used in palliative care processes for GB patients.en_US
dc.identifier.doi10.1016/j.neuro.2021.10.006
dc.identifier.endpage230en_US
dc.identifier.issn0161-813X
dc.identifier.issn1872-9711
dc.identifier.pmid34687775en_US
dc.identifier.scopus2-s2.0-85117576540en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage219en_US
dc.identifier.urihttps://doi.org/10.1016/j.neuro.2021.10.006
dc.identifier.urihttps://hdl.handle.net/20.500.14551/21278
dc.identifier.volume87en_US
dc.identifier.wosWOS:000712094900004en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relation.ispartofNeurotoxicologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectGalaxolide (HHCB)en_US
dc.subjectTonalide (AHTN)en_US
dc.subjectMetastatic Potentialen_US
dc.subjectAngio-Mirsen_US
dc.subjectGlioblastomaen_US
dc.subjectU87 MG Cellsen_US
dc.subjectBlood-Brain-Barrieren_US
dc.subjectPersonal-Care Productsen_US
dc.subjectPolycyclic Musks Hhcben_US
dc.subjectSynthetic Musksen_US
dc.subjectCell-Proliferationen_US
dc.subjectMir-17-92 Clusteren_US
dc.subjectAngiogenic Switchen_US
dc.subjectOxidative Stressen_US
dc.subjectOncogenic Roleen_US
dc.subjectBreast-Canceren_US
dc.titleProlonged sub-lethal exposure to galaxolide (HHCB) and tonalide (AHTN) promotes the metastatic potential of glioblastoma tumor spheroidsen_US
dc.typeArticleen_US

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