Bisphenol A induce ovarian cancer cell migration via the MAPK and PI3K/Akt signalling pathways

Toxicol Lett. 2014 Sep 2;229(2):357-65. doi: 10.1016/j.toxlet.2014.07.001. Epub 2014 Jul 2.

Abstract

Bisphenol A (BPA), is present in a multitude of products, including food and water containers, food can linings, dentistry sealants, and thermal paper. BPA can induce the growth of human ovarian cancer cell lines. Reduction of adhesion and the initiation of metastasis are important events in cancer progression; therefore, this study investigated the effects of BPA (0.1-100nM) on the migration of OVCAR-3 ovarian cancer cells and the expression levels of metalloproteinases (MMPs) and cadherins. The oestrogenic compound 17β-estradiol (40nM) was used as a positive control for estrogenic properties of bisphenol A. BPA stimulated cell migration, and the effect of BPA was similar to that of 17β-estradiol. BPA-induced cell migration was accompanied by up-regulation of the migration-related factors MMP-2, MMP-9 and N-cadherin, but E-cadherin expression and activity was unaffected. The stimulatory effects of BPA on cell migration were abolished by pre-treatment of the cells with inhibitors of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase pathways (PI3K). In conclusion, the results presented here show that BPA induces OVCAR-3 cells migration by activating MAPK and PI3K/Akt signalling pathways.

Keywords: Akt; Bisphenol A; ERK1/2; Migration; OVCAR-3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzhydryl Compounds / pharmacology
  • Benzhydryl Compounds / toxicity*
  • Blotting, Western
  • Carcinogens / pharmacology
  • Carcinogens / toxicity*
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Female
  • Humans
  • MAP Kinase Kinase 2 / drug effects*
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Ovarian Neoplasms / diagnosis*
  • Phenols / pharmacology
  • Phenols / toxicity*
  • Phosphatidylinositol 3-Kinases / drug effects*
  • Proto-Oncogene Proteins c-akt / drug effects*
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction / drug effects*

Substances

  • Benzhydryl Compounds
  • Carcinogens
  • Phenols
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • MAP Kinase Kinase 2
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • bisphenol A