Bisphenol S (BPS) induces glioblastoma progression via regulation of EZH2-mediated PI3K/AKT/mTOR pathway in U87-MG cells

Toxicology. 2024 Sep:507:153898. doi: 10.1016/j.tox.2024.153898. Epub 2024 Jul 18.

Abstract

Bisphenol S (BPS), an alternative to bisphenol A (BPA), exerts proliferative effects similar to those of BPA. BPS is a representative endocrine disruptor associated with cancer progression. However, the mechanisms underlying BPS-induced glioblastoma progression are not fully understood. To investigate the effects of BPS on glioblastoma, U-87 MG cancer cell lines were exposed to BPS. The study focused on analyzing the proliferation and migration of U-87 MG cells. Furthermore, the involvement of the enhancer of the zeste homolog 2 (EZH2)-mediated phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of the rapamycin (mTOR) pathway was examined. Pharmacological approaches were employed to inhibit EZH2 activity and observe its effects on BPS-induced changes. The results indicated that BPS promoted the proliferation and migration of U-87 MG cells at a concentration of 0.1 µM. These changes appeared to be linked to the activation of the EZH2-mediated PI3K/AKT/mTOR pathway. Moreover, inhibiting EZH2 activity using pharmacological approaches restored the BPS-mediated induction of proliferation and migration. In conclusion, the results of this study indicated that BPS induces glioblastoma progression through EZH2 upregulation. Therefore, targeting the EZH2-mediated PI3K/AKT/mTOR pathway could be considered a potential therapeutic strategy for the treatment of glioblastoma.

Keywords: Bisphenol S (BPS); EZH2; Glioblastoma; Migration; PI3K/Akt/mTOR pathway; Proliferation.

MeSH terms

  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement* / drug effects
  • Cell Proliferation* / drug effects
  • Disease Progression
  • Endocrine Disruptors / toxicity
  • Enhancer of Zeste Homolog 2 Protein* / metabolism
  • Glioblastoma* / drug therapy
  • Glioblastoma* / metabolism
  • Glioblastoma* / pathology
  • Humans
  • Phenols* / pharmacology
  • Phenols* / toxicity
  • Phosphatidylinositol 3-Kinase / metabolism
  • Phosphatidylinositol 3-Kinases* / metabolism
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Signal Transduction* / drug effects
  • Sulfones* / pharmacology
  • Sulfones* / toxicity
  • TOR Serine-Threonine Kinases* / metabolism

Substances

  • Enhancer of Zeste Homolog 2 Protein
  • TOR Serine-Threonine Kinases
  • EZH2 protein, human
  • Phenols
  • bisphenol S
  • Proto-Oncogene Proteins c-akt
  • MTOR protein, human
  • Phosphatidylinositol 3-Kinases
  • Sulfones
  • Endocrine Disruptors
  • Phosphatidylinositol 3-Kinase