An endogenous aryl hydrocarbon receptor ligand inhibits proliferation and migration of human ovarian cancer cells

Cancer Lett. 2013 Oct 28;340(1):63-71. doi: 10.1016/j.canlet.2013.06.026. Epub 2013 Jul 9.

Abstract

The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor mediates many biological processes. Herein, we investigated if 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE, an endogenous AhR ligand) regulated proliferation and migration of human ovarian cancer cells via AhR. We found that AhR was widely present in many histotypes of ovarian cancer tissues. ITE suppressed OVCAR-3 cell proliferation and SKOV-3 cell migration in vitro, which were blocked by AhR knockdown. ITE also suppressed OVCAR-3 cell growth in mice. These data suggest that the ITE might potentially be used for therapeutic intervention for at least a subset of human ovarian cancer.

Keywords: Aryl hydrocarbon receptor; Growth; ITE; Ovarian cancer cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects*
  • Cytochrome P-450 CYP1A1 / genetics
  • Cytochrome P-450 CYP1A1 / metabolism
  • Female
  • Gene Expression
  • Gene Knockdown Techniques
  • Humans
  • Indoles / pharmacology*
  • Ligands
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / metabolism*
  • Thiazoles / pharmacology*
  • Tissue Array Analysis
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • 2-(1'H-indole-3'-carbonyl)thiazole-4-carboxylic acid methyl ester
  • Antineoplastic Agents
  • Indoles
  • Ligands
  • Receptors, Aryl Hydrocarbon
  • Thiazoles
  • CYP1A1 protein, human
  • Cytochrome P-450 CYP1A1