title: Phthalates deregulate cell proliferation, but not neuroendocrine transdifferentiation, in human LNCaP prostate cancer cell model.
abstract: Phthalate esters are ubiquitous environmental pollutants widely used as plasticizers, which have been shown to interfere with both endocrine regulation and development of reproductive organs. In the present study, we examined the impact of diethylhexyl phthalate (DEHP) and dibutyl phthalate (DBP) on the proliferation of androgen-sensitive human prostate carcinoma LNCaP cells and related events. The results showed that both compounds were able to inhibit cell cycle progression in a dose-dependent manner. However, only DEHP was found to weakly reduce androgen receptor (AR) protein levels after long-term exposure, while only DBP partially inhibited expression of the prostate-specific antigen (KLK3) gene, a model AR transcriptional target. This indicated that inhibition of cell proliferation was likely independent of any AR modulations. Both phthalates induced suppression of cell proliferation, but none of them affected the levels of markers associated with neuroendocrine transdifferentiation (NED) in LNCaP cells. Taken together, the presented data indicate that phthalates may exert long-term negative effects on the proliferation of prostate epithelial cells derived from the carcinoma model, which are, nevertheless, largely independent of the modulation of AR expression/activity, and which do not alter further processes associated with NED.
authors.affiliation: Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, v. v. i., Brno, Czech Republic.
authors.forename: E
authors.initials: E
authors.lastname: Hrubá
authors.affiliation: Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, v. v. i., Brno, Czech Republic.
authors.forename: Z
authors.initials: Z
authors.lastname: Pernicová
authors.affiliation: Department of Chemistry and Toxicology, Veterinary Research Institute, Brno, Czech Republic.
authors.forename: L
authors.initials: L
authors.lastname: Pálková
authors.affiliation: Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, v. v. i., Brno, Czech Republic.
authors.forename: K
authors.initials: K
authors.lastname: Souček
authors.affiliation: Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, v. v. i., Brno, Czech Republic.
authors.forename: J
authors.initials: J
authors.lastname: Vondráček
authors.affiliation: Department of Chemistry and Toxicology, Veterinary Research Institute, Brno, Czech Republic.
authors.forename: M
authors.initials: M
authors.lastname: Machala
mesh_terms: D002452:Cell Count; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D054338:Cell Transdifferentiation / Q000187:drug effects*; D003993:Dibutyl Phthalate / Q000633:toxicity; D004051:Diethylhexyl Phthalate / Q000633:toxicity; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D008954:Models, Biological; D055099:Neuroendocrine Cells / Q000187:drug effects / Q000473:pathology*; D010795:Phthalic Acids / Q000633:toxicity*; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D010795:Phthalic Acids; D012333:RNA, Messenger; D003993:Dibutyl Phthalate; C032279:phthalic acid; D004051:Diethylhexyl Phthalate; D017430:Prostate-Specific Antigen