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

Abstract

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.