The inflammation and estrogen metabolism impacts of polychlorinated biphenyls on endometrial cancer cells

Toxicol In Vitro. 2015 Mar;29(2):308-13. doi: 10.1016/j.tiv.2014.11.008. Epub 2014 Nov 26.

Abstract

Polychlorinated biphenyls (PCBs) are persistent and bio-accumulative chemicals that provoke a wide range of toxic effects. Their adverse impacts on the reproductive system are of great concern, however, the effects of PCBs on endometrium are still unclear. In the study, the endometrial adenocarcinoma Ishikawa cells were exposed to both dioxin-like CB126 and non-dioxin-like CB153 at the nominal concentrations of 0.3, 3, and 30μM. The inflammatory and endocrine effects were detected after treatment by PCBs. Results showed that CB126 stimulated the proliferation of Ishikawa cells at lower concentrations of 0.3 and 3μM. By contrast, CB153 did not affect the viability of the cells. Both congeners exerted the stimulatory effects on the enzymatic activity of SOD1. CB126 decreased the abundance of Interleukin-8 both at the mRNA and protein levels. Blocking of estrogen receptor or aryl hydrocarbon receptor by the antagonist abolished the effects of CB126 on the expressions of inflammatory factors. The levels of testosterone and 17beta-estradiol were not changed after exposure to lower doses of PCBs. In accordance, PCBs did not affect the mRNA expressions of estrogen metabolism-related genes. In all, our study revealed that PCBs affected the expression of inflammatory factors through ER and AHR receptors, however, no toxic effects were observed on estrogen metabolism.

Keywords: CB126; Endocrine; Estrogen metabolism; Inflammation; Ishikawa cells; Polychlorinated biphenyls.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cytochrome P-450 CYP1A1 / genetics
  • Endometrial Neoplasms / metabolism*
  • Estradiol / metabolism
  • Estrogen Antagonists / toxicity
  • Estrogens / metabolism*
  • Female
  • Humans
  • Inflammation / metabolism*
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Polychlorinated Biphenyls / toxicity*
  • RNA, Messenger / metabolism
  • Receptors, Aryl Hydrocarbon / antagonists & inhibitors
  • Receptors, Aryl Hydrocarbon / metabolism
  • Receptors, Estrogen / antagonists & inhibitors
  • Receptors, Estrogen / metabolism
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase-1
  • Testosterone / metabolism

Substances

  • CXCL8 protein, human
  • Estrogen Antagonists
  • Estrogens
  • Interleukin-8
  • RNA, Messenger
  • Receptors, Aryl Hydrocarbon
  • Receptors, Estrogen
  • SOD1 protein, human
  • Testosterone
  • Estradiol
  • Polychlorinated Biphenyls
  • CYP1A1 protein, human
  • Cytochrome P-450 CYP1A1
  • Superoxide Dismutase
  • Superoxide Dismutase-1
  • 3,4,5,3',4'-pentachlorobiphenyl
  • 2,4,5,2',4',5'-hexachlorobiphenyl