The Flame-Retardant Tris(1,3-dichloro-2-propyl) Phosphate Represses Androgen Signaling in Human Prostate Cancer Cell Lines

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.

Journal of biochemical and molecular toxicology. 2015 Dec 28 [Epub ahead of print]

Alexandra R Reers, Margaret L Eng, Tony D Williams, John E Elliott, Michael E Cox, Timothy V Beischlag

Department of Biological Sciences, Simon Fraser University, Burnaby, B. C. , V5A 1S6, Canada. , Department of Biological Sciences, Simon Fraser University, Burnaby, B. C. , V5A 1S6, Canada. , 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. , Vancouver Prostate Centre, Vancouver Coastal Health Research Institute, Vancouver, B. C. , V6H 3Z6, Canada. , Faculty of Health Sciences, Simon Fraser University, Burnaby, B. C. , V5A 1S6, Canada. 

PubMed

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