Effect of bisphenol-A on the expression of selected genes involved in cell cycle and apoptosis in the OVCAR-3 cell line

Toxicol Lett. 2011 Apr 10;202(1):30-5. doi: 10.1016/j.toxlet.2011.01.015. Epub 2011 Jan 26.

Abstract

To support the argument that bisphenol-A (BPA) poses a risk for ovarian cancer, OVCAR-3 cell line was exposed to environmentally relevant concentration of BPA. Expression of selected genes involved in cell cycle and apoptosis were evaluated by real-time PCR. In a dose-dependent manner, BPA increased OVCAR-3 cell proliferation and decreased caspase-3 activity, but it had no effect on DNA fragmentation. We noted 1.2-1.5-fold induction of genes responsible for inducing cell proliferation and 1.2-46-fold suppression of genes responsible for inhibition of proliferation. Moreover, 1.6-8-fold suppression of genes involved in the extrinsic apoptotic pathway was observed. In parallel, 1.3-2.5-fold suppression pro-apoptotic genes and 1.6-51-fold induction of pro-survival genes involved in the intrinsic apoptotic pathway were observed. Additionally, 1.7-fold induction of p53 and 5-fold induction of endonuclease G genes involved in CAD-independent DNA fragmentation were noted under the influence of BPA. In conclusion, we hypothesize that induction of p53 and suppression of caspase-3 and 7 gene expression observed in this study activate the DNA repair process. Therefore, despite the observed induction of endo G gene expression, the action of BPA on DNA fragmentation was not observed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Benzhydryl Compounds
  • Carcinogenicity Tests
  • Carcinogens, Environmental / toxicity*
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Caspase 7 / genetics
  • Caspase 7 / metabolism
  • Cell Cycle / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Estrogens, Non-Steroidal / toxicity*
  • Female
  • Gene Expression / drug effects
  • Humans
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Phenols / toxicity*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Benzhydryl Compounds
  • Carcinogens, Environmental
  • Estrogens, Non-Steroidal
  • Phenols
  • Tumor Suppressor Protein p53
  • Caspase 3
  • Caspase 7
  • bisphenol A