title: The Flame-Retardant Tris(1,3-dichloro-2-propyl) Phosphate Represses Androgen Signaling in Human Prostate Cancer Cell Lines.
abstract: The effects of six organophosphate flame retardants (OPFRs) tris(2-butoxyethyl) phosphate, tris(2-chloroethyl) phosphate, tris(1-chloro-2-propyl) phosphate, tris(methylphenyl) phosphate, tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), and triethyl phosphate on the activities of androgen receptor (AR), estrogen receptor (ER), and aryl hydrocarbon receptor (AhR) were assessed in human prostate and endometrial cancer cells. OPFRs had no effect on ER or AhR target gene activation in ECC-1 cells. The effect of TDCIPP on mRNA and protein accumulation of AR target genes was examined further. AR-inducible gene and protein expression were significantly altered by TDCIPP exposure and repressed PSA levels in conditioned media of prostate cancer cells. We demonstrated that TDCIPP has no affinity for the AR ligand binding domain (AR-LBD) and exerts its antiandrogenic effects in a noncompetitive fashion. Thus, the clinical relevance of TDCIPP exposure on prostate cancer detection and progression to a therapeutically refractile state ought to be investigated further.
authors.affiliation: Department of Biological Sciences, Simon Fraser University, Burnaby, B.C., V5A 1S6, Canada.
authors.forename: Alexandra R
authors.initials: AR
authors.lastname: Reers
authors.affiliation: Department of Biological Sciences, Simon Fraser University, Burnaby, B.C., V5A 1S6, Canada.|Pacific Wildlife Research Center, Environment Canada, Delta, B.C., V4K 3N2, Canada.
authors.forename: Margaret L
authors.initials: ML
authors.lastname: Eng
authors.affiliation: Department of Biological Sciences, Simon Fraser University, Burnaby, B.C., V5A 1S6, Canada.
authors.forename: Tony D
authors.initials: TD
authors.lastname: Williams
authors.affiliation: Pacific Wildlife Research Center, Environment Canada, Delta, B.C., V4K 3N2, Canada.
authors.forename: John E
authors.initials: JE
authors.lastname: Elliott
authors.affiliation: The Vancouver Prostate Centre, Vancouver Coastal Health Research Institute, Vancouver, B.C., V6H 3Z6, Canada.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Cox
authors.affiliation: Faculty of Health Sciences, Simon Fraser University, Burnaby, B.C., V5A 1S6, Canada. tvb@sfu.ca.
authors.forename: Timothy V
authors.initials: TV
authors.lastname: Beischlag
mesh_terms: D045744:Cell Line, Tumor; D052244:Endocrine Disruptors / Q000494:pharmacology*; D004717:Endometrium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004785:Environmental Pollutants / Q000494:pharmacology*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D005260:Female; D005411:Flame Retardants / Q000494:pharmacology*; D005786:Gene Expression Regulation; D006801:Humans; D007610:Kallikreins / Q000235:genetics / Q000378:metabolism; D008297:Male; D010755:Organophosphates / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D011467:Prostate / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics
chemical_list: C410798:AR protein, human; C506487:ESR1 protein, human; D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D047628:Estrogen Receptor alpha; D005411:Flame Retardants; D010755:Organophosphates; D009943:Organophosphorus Compounds; D012333:RNA, Messenger; D011944:Receptors, Androgen; D018336:Receptors, Aryl Hydrocarbon; C016805:tris(1,3-dichloro-2-propyl)phosphate; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen; C009549:triethyl phosphate; C013320:tris(2-butoxyethyl) phosphate
keywords: Androgen Receptor; Aryl Hydrocarbon Receptor; Endocrine Disruptor; Estrogen Receptor; LNCaP; Organophosphate Flame Retardants