Antiandrogenic mechanisms of pesticides in human LNCaP prostate and H295R adrenocortical carcinoma cells.

Several pesticides suspected or known to have endocrine disrupting effects were screened for pro- or antiandrogenic properties by determining their effects on proliferation, prostatic-specific antigen (PSA) secretion and androgen receptor (AR) expression, and AR phosphorylation in androgen-dependent LNCaP human prostate cancer cells, as well as on the expression and catalytic activity of the enzyme CYP17 in H295R human adrenocortical carcinoma cells, an in vitro model of steroidogenesis. Effects on SRD5A gene expression were determined in both cell lines. Benomyl, vinclozolin, and prochloraz, but not atrazine, concentration dependently (1-30 μM) decreased dihydrotestosterone (DHT)-stimulated proliferation of LNCaP cells.

Proliferative and androgenic effects of indirubin derivatives in LNCaP human prostate cancer cells at sub-apoptotic concentrations.

Certain indirubin derivatives are potent cyclin-dependent kinase (CDK) and glycogen synthase kinase (GSK-3β) inhibitors and may be effective against various cancers. We evaluated the effects of aloisine A, alsterpaullone, aminopurvalanol, indirubin-3'-oxime, 6-Br-indirubin-3'-oxime, kenpaullone, olomoucine and roscovitine on cell proliferation, prostate-specific antigen (PSA) expression, androgen receptor (AR) activation, and GSK-3β and β-catenin expression in androgen-dependent LNCaP human prostate cancer cells. Effects were also evaluated in MDA-kb2 human breast cancer cells containing an AR-responsive luciferase construct.

Evaluation of a bioluminescent mouse model expressing aromatase PII-promoter-controlled luciferase as a tool for the study of endocrine disrupting chemicals.

Dysfunction of the enzyme aromatase (CYP19) is associated with endocrine pathologies such as osteoporosis, impaired fertility and development of hormone-dependent cancers. Certain endocrine disrupting chemicals affect aromatase expression and activity in vitro, but little is known about their ability to do so in vivo. We evaluated a bioluminescent mouse model (LPTA®)CD-1-Tg(Cyp19-luc)-Xen) expressing luciferase under control of the gonadal aromatase pII promoter as an in vivo screening tool for chemicals that may affect aromatase expression.