Characterization of Dopamine Receptor Associated Drugs on the Proliferation and Apoptosis of Prostate Cancer Cell Lines.

BACKGROUND Dopamine receptor (DR) gene family play an essential role in the regulation of interleukin-6 (IL-6) production. Our prior analysis of human prostate biopsy samples demonstrated the increased expression of IL-6 and a down regulating trend for dopamine receptor gene family. OBJECTIVE The objective was to investigate the expression of dopamine receptors, their catabolizing enzyme and IL-6 in prostate cancer cell lines and assess pharmacological effect of dopamine receptor modulators as a novel class of drugs repurposed for treatment of prostate cancer. METHODS The therapeutic effect of dopamine, DR agonists, and DR antagonist were examined using LNCaP and PC3 cell lines.CellviabilityandproliferationwereassessedbyMTTassayandproliferatingcellnuclearantigenexpressionanalysis, respectively. Furthermore, bax/bcl2 ratio, immunofluorescence assay and flow cytometric assay were performed for apoptosis analysis. RT-q PCR analysis was used to characterize relative expression of dopamine-related genes, catabolic enzyme catechol-o-methyl-transferase (COMT) and IL-6 before and after treatment to assess the therapeutic effects of drugs. RESULTS LNCaP cells express DRD1, DRD2, DRD5 and COMT genes and PC3 cells only express IL-6 gene. In-vitro, dopamine receptor agonists reduced cell viability of LNCaP and PC3 cells. In contrast, dopamine and dopamine receptor antagonist significantly increased tumor growth in PC3 cells. CONCLUSION Our results offer novel suggestion for a pathogenic role of dopamine receptor signaling in prostate cancer adenocarcinoma and indicates that modulators of DR-IL-6 pathway, including FDA-approved drug bromocriptine, might be utilized as novel drug repurposing strategy.