Antiangiogenic Effect of Dopamine and Dopaminergic Agonists as an Adjuvant Therapeutic Option in the Treatment of Cancer, Endometriosis, and Osteoarthritis

Abstract

Dopamine (DA) and dopamine agonists (DA-Ag) have shown antiangiogenic potential through the vascular endothelial growth factor (VEGF) pathway. They inhibit VEGF and VEGF receptor 2 (VEGFR 2) functions through the dopamine receptor D2 (D2R), preventing important angiogenesis-related processes such as proliferation, migration, and vascular permeability. However, few studies have demonstrated the antiangiogenic mechanism and efficacy of DA and DA-Ag in diseases such as cancer, endometriosis, and osteoarthritis (OA). Therefore, the objective of this review was to describe the mechanisms of the antiangiogenic action of the DA-D2R/VEGF-VEGFR 2 system and to compile related findings from experimental studies and clinical trials on cancer, endometriosis, and OA. Advanced searches were performed in PubMed, Web of Science, SciFinder, ProQuest, EBSCO, Scopus, Science Direct, Google Scholar, PubChem, NCBI Bookshelf, DrugBank, livertox, and Clinical Trials. Articles explaining the antiangiogenic effect of DA and DA-Ag in research articles, meta-analyses, books, reviews, databases, and clinical trials were considered. DA and DA-Ag have an antiangiogenic effect that could reinforce the treatment of diseases that do not yet have a fully curative treatment, such as cancer, endometriosis, and OA. In addition, DA and DA-Ag could present advantages over other angiogenic inhibitors, such as monoclonal antibodies.

Angiogenesis signaling in endometriosis: Molecules, diagnosis and treatment (Review)

“…Cabergoline, a dopamine agonist, exerts anti-angiogenic effects by inducing endocytosis of VEGFR-2 in endothelial cells, leading to decreased and inactivated VEGF-VEGFR-2 binding ( 112 ). D2-ags are as powerful as standard anti-angiogenic compounds in interfering with angiogenesis and lesion size ( 111 , 113 ). In addition, in a prospective clinical trial, D2-ags were shown to be superior to luteinizing hormone-releasing hormone agonists in decreasing size of endometrial tumors, with fewer drug side effects, easier administration and lower price ( 112 ).…”