Abstract
Cancer is one of the leading causes of mortality worldwide. Even with the advances of pharmaceutical industry and treatments, the mortality rate for various types of cancer remains high. In particular, phenotypic alterations of tumor cells concerning drug efflux, migratory and invasive capabilities may represent a hurdle for cancer treatment and contribute to poor prognosis. In the present study, we investigated the effects of polybrominated diphenyl ethers (PBDEs) used as flame retardants on phenotypic features of melanoma cells that are important for cancer. Murine melanoma B16-F1 (less metastatic) and B16-F10 (more metastatic) cells were exposed to 0.01–1.0 nM of BDE-47 (2,2′,4,4′-tetrabromodiphenyl ether), BDE-99 (2,2′,4,4′,5-pentabromodiphenyl ether), and the mixture of both (at 0.01 nM) for 24 h (acute exposure) and 15 days (chronic exposure). The polybrominated diphenyl ethers (PBDEs) did not affect cell viability but led to increased drug efflux transporter activity, cell migration, and colony formation, as well as overexpression of Abcc2 (ATP-binding cassette subfamily C member 2), Mmp-2 (matrix metalloproteinase-2), Mmp-9 (matrix metalloproteinase-9), and Tp53 (tumor protein p53) genes and downregulation of Timp-3 (tissue inhibitor of metalloproteinase 3) gene in B16-F10 cells. These effects are consistent with increased aggressiveness and malignancy of tumors due to exposure to the flame retardants and raise some concerns on the effects such chemicals may have on melanoma treatment and cancer prognosis.
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Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.
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Acknowledgements
The authors thank CNPq, CAPES, UFPR, and Fundação Araucária for funding this research and the Center for Advanced Fluorescence Technologies (CTAF) for technical support.
Funding
This study was supported by the Brazilian Council for Science and Technology Agency–CNPq (Finance Code 480707/2013-8, 428830/2018-8), Fundação Araucária de Apoio ao Desenvolvimento Científico e Tecnológico do Paraná (Finance Code 006/2017), Universidade Federal do Paraná (UFPR), and Coordination for the Improvement of Higher Education Personnel–CAPES (Finance Code 001).
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Gisleine Jarenko Steil: Investigation, formal analysis, and writing-original draft
João Luiz Aldinucci Buzzo: Formal analysis and writing-review and editing
Ciro Alberto de Oliveira Ribeiro: Conceptualization, project administration, resources, and writing-review and editing
Francisco Filipak Neto: Conceptualization, formal analysis, resources, supervision, visualization, writing-original draft, and writing-review and editing
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Highlights
B16-F1 and B16-F10 cells were exposed to BDE-47 and BDE-99 for 24 h and 15 days.
PBDEs did not affect cell viability, but the morphology of B16-F1 cells changed.
Activity of drug efflux transporters and Abcc2 expression increased in B16-F10 cells.
Migration and colony formation increased, and Mmp-9/Timp-3 expression was altered.
B16-F10 cells may become more aggressive and metastatic after exposure to both PBDEs.
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Steil, .J., Buzzo, J.L.A., de Oliveira Ribeiro, C.A. et al. Polybrominated diphenyl ethers BDE-47 and BDE-99 modulate murine melanoma cell phenotype in vitro. Environ Sci Pollut Res 29, 11291–11303 (2022). https://doi.org/10.1007/s11356-021-16455-0
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DOI: https://doi.org/10.1007/s11356-021-16455-0