title: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) inhibits human ovarian cancer cell proliferation.
abstract: OBJECTIVE
  The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, mediates a broad spectrum of biological processes, including ovarian growth and ovulation. Recently, we found that an endogenous AhR ligand (ITE) can inhibit ovarian cancer proliferation and migration via the AhR. Here, we tested whether 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, an exogenous AhR ligand) may exert similar anti-ovarian cancer activities using human ovarian cancer and non-cancerous human ovarian surface epithelial cells.
  
  
  METHODS
  Two human ovarian cancer cell lines (SKOV-3 and OVCAR-3) and one human ovarian surface epithelial cell line (IOSE-385) were used. Cell proliferation and migration activities were determined using crystal violet and FluoroBlok insert system assays, respectively. AhR protein expression was assessed by Western blotting. Expression of cytochrome P450, family 1, member A1 (CYP1A1) and member B1 (CYP1B1) mRNA was assessed by qPCR. Small interfering RNAs (siRNAs) were used to knock down AhR expression.
  
  
  RESULTS
  We found that TCDD dose-dependently suppressed OVCAR-3 cell proliferation, with a maximum effect (~70% reduction) at 100 nM. However, TCDD did not affect SKOV-3 and IOSE-385 cell proliferation and migration. The estimated IC50 of TCDD for inhibiting OVCAR-3 cell proliferation was 4.6 nM. At 10 nM, TCDD time-dependently decreased AhR protein levels, while it significantly increased CYP1A1 and CYP1B1 mRNA levels in SKOV-3, OVCAR-3 and IOSE-385 cells, indicating activation of AhR signaling. siRNA-mediated AhR knockdown readily blocked TCDD-mediated suppression of OVCAR-3 cell proliferation.
  
  
  CONCLUSIONS
  Our data indicate that TCDD can suppress human ovarian cancer cell proliferation via the AhR signaling pathway and that TCDD exhibits an anti-proliferative activity in at least a subset of human ovarian cancer cells.
authors.affiliation: Department of Obstetrics and Gynecology, University of Wisconsin, 202 S. Park St., Madison, WI, 53715, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Yi-Zhou
authors.initials: YZ
authors.lastname: Jiang
authors.forename: Xin-Wen
authors.initials: XW
authors.lastname: Chang
authors.forename: Cai-Feng
authors.initials: CF
authors.lastname: Dai
authors.forename: Jing
authors.initials: J
authors.lastname: Zheng
mesh_terms: D000970:Antineoplastic Agents; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000378:metabolism*; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon