The global burden of breast cancer necessitates innovative adjunct therapies to address conventional treatment limitations. This study investigated the antitumour potential of repurposing propranolol (β-adrenergic blocker) and dopamine (dopaminergic agonist) in comparison with tamoxifen, utilizing a DMBA-induced mammary carcinoma rat model. In this preclinical in vivo study, sixty female albino rats were enrolled; fifty rats underwent mammary tumour induction and, upon developing palpable tumours, were allocated into five treatment groups (n=10 per group), while the remaining ten rats served as plain controls. Assessment parameters include tumour volume, proliferative (Ki-67) and apoptotic (Caspase-3) markers, serum VEGF, and hepatic oxidative stress (MDA and GSH). Findings revealed that dopamine and tamoxifen significantly suppressed tumour growth by week four, while propranolol exhibited a moderate effect. Tamoxifen and dopamine effectively suppressed cellular proliferation, as indicated by reduced Ki-67 expression. Furthermore, all interventions successfully triggered apoptosis, evidenced by significantly elevated Caspase-3 levels. Notably, dopamine exhibited the most potent anti-angiogenic profile, restoring serum VEGF to near-normal concentrations. While tamoxifen and propranolol effectively mitigated hepatic oxidative stress, dopamine displayed limited antioxidant efficacy. In conclusion, the present findings indicate that the pharmacological targeting of β-adrenergic and dopaminergic signalling cascades yields significant antitumour efficacy. These pathways represent highly promising candidates for adjunct breast cancer management, justifying more extensive clinical evaluations of these repurposed therapeutic agents.
Fatma M. EL-Sayed1*, Wessam F. EL-Hadidy1, Amani H. Kazem1, Maged W. Helmy2,3, Remonda E. Rizk1 (Mon,) studied this question.