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 downregulating 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 the treatment of prostate cancer.
Methods: The therapeutic effect of dopamine, DR agonists, and DR antagonist were examined using LNCaP and PC3 cell lines. Cell viability and proliferation were assessed by MTT assay and proliferating cell nuclear antigen expression analysis, respectively. Furthermore, bax/bcl2 ratio, immunofluorescence assay and flow cytometric assay were performed for apoptosis analysis. RT- qPCR analysis was used to characterize the 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.