The effects of prochloraz on the levels of nuclear receptor genes expressions and global DNA methylation in human prostate carcinoma cells

Abstract

Background and Aims: Prochloraz (PCZ) is an imidazole fungicide which is used in agriculture and gardening. PCZ, with endocrine disrupting effect, disrupts reproductive and developmental functions. Previously, the effects of PCZ on the estrogen andandrogen receptors have been shown in vitro and in vivo. Because of endocrine disrupting effects, PCZ could influence nuclearreceptors which acted as ER and AR antagonists. Besides, PCZ has been thought to have no genotoxic effects. Therefore, weaimed to investigate possible effects of PCZ on nuclear receptor genes and epigenetic mechanisms in human prostate carcinoma (PC-3) cells.Methods: In the present study, MTT and LDH tests were applied to evaluate the cell viability. Expression levels of nuclearreceptor genes such as AhR, PXR, PPARα, PPARγ were studied on real-time quantitative PCR. For global DNA methylationanalysis, the levels of 5-methylcytosine (5-mC%) were measured by elisa kit.Results: According to MTT and LDH test results, IC50 value of PCZ has been determined as 144.19 and 116.65 μM, respectively. There were significant changes for the expression levels of AhR, PPARα and PPARγ genes after 5-50 μM of PCZ treatments. 5 and 50 μM of PCZ decreased the levels of 5-mC% in the rates of 22.6% and 26.9%, respectively.Conclusion: It has been suggested that PCZ may cause alterations on the expressions of nuclear receptor genes which couldbe related to endocrine disrupting effects and may have implications on global DNA methylation.