Brominated flame retardants effect in MCF-7 cells: Impact on vitamin D pathway

Sara Sousa, Maria Luz Maia, Diogo Pestana, Diana Teixeira, Miguel Ângelo-Dias, Catarina Martins, Luís Miguel Borrego, Cristina Delerue-Matos, Conceição Calhau, Valentina Fernandes Domingues, Ana Faria

Research output: Contribution to journalArticlepeer-review

Abstract

Brominated flame retardants (BFRs) are persistent environmental pollutants, allowing a constant human exposure which carries several health risks, including the occurrence of breast cancer and vitamin D deficiency. Vitamin D inhibits cell growth and is negatively associated with breast cancer risk. The effect of BFRs in breast cancer and vitamin D pathway is still poorly understood. MCF-7 cells were treated with hexabromocyclododecane (HBCD), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB), hexabromobenzene (HBB) and pentabromotoluene (PBT) using short and long-term exposure protocols. Viability, proliferation, migration, cell cycle and gene expression were assessed. Gene expression of hVDBP and hCYP2R1 was also evaluated in hepatocytes. Long-term exposure of MCF-7 cells to HBB increased cell proliferation and migration, consequently increasing MMP-9 expression. The vitamin D pathway was also altered by BFRs: cells appeared less prepared to activate and transport vitamin D and the signaling, action and inactivation mechanisms were diminished in the presence of BFRs. Untreated MCF-7 cells showed cell cycle arrest in phase G0/G1 in the presence of activated vitamin D. However, when MCF-7 cells were exposed to BFRs, cell cycle was arrested in phase G2/M, possibly due to DNA damage. Nonetheless, calcitriol seems to be able to mitigate the effect of some BFRs exposure, e.g. PBT.

Original languageEnglish
Article number106079
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume219
DOIs
Publication statusPublished - May 2022

Keywords

  • 2-ethylhexyl-2,3,4,5-tetrabromobenzoate
  • Breast cancer
  • Calcitriol
  • Hexabromobenzene
  • Hexabromocyclododecane
  • Pentabromotoluene

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