Effect of benzophenone-1 and octylphenol on the regulation of epithelial-mesenchymal transition via an estrogen receptor-dependent pathway in estrogen receptor expressing ovarian cancer cells

Food Chem Toxicol. 2016 Jul:93:58-65. doi: 10.1016/j.fct.2016.04.026. Epub 2016 May 1.

Abstract

Epithelial-mesenchymal transition (EMT) is an important process in embryonic development and cancer progression and metastasis. EMT is influenced by 17β-estradiol (E2), an endogenous estrogen. Benzophenone-1 (2,4-dihydroxybenzophenone, BP-1) and 4-tert-octylphenol (OP) are suspected endocrine disrupting chemicals (EDCs) because they can exhibit estrogenic properties. In this study, we examined whether BP-1 and OP can lead to EMT of BG-1 ovarian cancer cells expressing estrogen receptors (ERs). A wound healing assay and western blot assay were conducted to show the effect of BP-1 and OP on the migration of BG-1 cells and protein expression of EMT-related genes. BP-1 (10(-6) M) and OP (10(-6) M) significantly enhanced the migration capability of BG-1 cells by reducing the wounded area in the cell monolayer relative to the control, similar to E2 (10(-9) M). However, when BG-1 cells were co-treated with ICI 182,780, an ER antagonist, the uncovered area was maintained at the level of the control. N-cadherin, snail, and slug were increased by BP-1 and OP while E-cadherin was reduced compared to the control. However, this effect was also restored by co-treatment with ICI 182,780. Taken together, these results indicate that BP-1 and OP, the potential EDCs, may have the ability to induce ovarian cancer metastasis via regulation of the expression of EMT markers and migration of ER-expressing BG-1 ovarian cancer cells.

Keywords: Benzophenone-1; EMT; Octylphenol; Ovarian cancer.

MeSH terms

  • Benzophenones / pharmacology*
  • Blotting, Western
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Epithelial-Mesenchymal Transition / drug effects*
  • Female
  • Humans
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Phenols / pharmacology*
  • Receptors, Estrogen / metabolism*
  • Signal Transduction / drug effects*
  • Tumor Cells, Cultured

Substances

  • Benzophenones
  • Phenols
  • Receptors, Estrogen
  • octylphenol