Nonylphenol acts on prostate adenocarcinoma cells via estrogen molecular pathways

Ecotoxicol Environ Saf. 2019 Sep 30:180:412-419. doi: 10.1016/j.ecoenv.2019.05.035. Epub 2019 May 17.

Abstract

Estrogens play a role in the patho-physiology of the prostate. In the present work we studied the effects of nonylphenol (NP), a xenoestrogen, on human adenocarcinoma prostate cells (LNCaP). In order to understand molecular and cellular involvement, we observed the effects on cell cycle and we investigated the expression and the cellular localization of estrogen receptors and gene expression of cyclin D1, ki-67, c-myc, IL-8, IL-1β. We performed the same experiments with 17β-estradiol (E2), the most abundant estrogen circulating in nonpregnant humans in order to compare these two different substances. We demonstrated the ability of 1 × 10-10 M NP to induce proliferation of LNCaP, S-phase progression, increase of ERα expression and its translocation from the cytoplasm to the nucleus. Moreover, we observed an up-regulation of key target genes involved in cell cycle and inflammation process. Particularly, after NP treatment, IL-8 and IL-1β mRNA levels are increased more than 50% indicating a major NP involvement in inflammation processes than E2. These data suggest the proliferative effects of NP on prostate adenocarcinoma cells and highlight some aspects of molecular pathways involved in prostate responses to NP.

Keywords: EDCs; Estrogens; Nonylphenol; Prostate adenocarcinoma cells; Xenoestrogens.

MeSH terms

  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclin D1 / genetics
  • Environmental Pollutants / toxicity*
  • Estradiol / toxicity*
  • Estrogen Receptor alpha / metabolism*
  • Gene Expression / drug effects
  • Humans
  • Interleukin-1beta / genetics
  • Male
  • Phenols / toxicity*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*

Substances

  • CCND1 protein, human
  • ESR1 protein, human
  • Environmental Pollutants
  • Estrogen Receptor alpha
  • Interleukin-1beta
  • Phenols
  • Cyclin D1
  • Estradiol
  • nonylphenol