Endocrine disruptor agent nonyl phenol exerts an estrogen-like transcriptional activity on estrogen receptor positive breast cancer cells

Curr Med Chem. 2014;21(5):630-40. doi: 10.2174/09298673113209990169.

Abstract

Several substances widely dispersed in the environment including hormones, industrial by-products and pollutants exert hormone like activity affecting steroid-responsive physiological systems. These compounds, named endocrine disruptors, are suspected to affect the mammalian reproductive system. However it is still unclear whether these substances are able to elicit estrogen like activity at the low concentrations encountered in the environment. Here we compare the effects of the endocrine disruptor nonylphenol with the effects elicited by 17-β-estradiol on gene transcription in the human breast cancer cell line MCF7. The correlation of the nonylphenol induced gene expression alterations with a reference profile of estradiol treated cells shows that nonylphenol at a concentration of 100 nM exerts a significant effect on estrogen responsive gene transcription in MCF7 cells. Most of the genes regulated by 17-β-estradiol respond to the nonylphenol in the same direction though to a much lesser extent. Molecular modeling of the potential interaction of nonylphenol with the estrogen receptor α shows that nonylphenol is likely to bind to the estrogen receptor α.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Endocrine Disruptors / chemistry
  • Endocrine Disruptors / pharmacology*
  • Estradiol / pharmacology
  • Estrogen Receptor alpha / chemistry
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor alpha / metabolism
  • Female
  • Humans
  • MCF-7 Cells
  • Molecular Docking Simulation
  • Phenols / chemistry
  • Phenols / pharmacology*
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription, Genetic / drug effects*

Substances

  • ESR1 protein, human
  • Endocrine Disruptors
  • Estrogen Receptor alpha
  • MYBL1 protein, human
  • Phenols
  • Proto-Oncogene Proteins
  • Receptors, Estrogen
  • Trans-Activators
  • Estradiol
  • nonylphenol