Anti-carcinogenic effects of arecaidine but-2-ynyl ester tosylate on breast cancer: proliferation inhibition and activation of apoptosis.

backgroundBreast cancer (BC) is the most prevalent cancer among women globally and is notoriously difficult to treat due to its heterogeneous nature and the lack of an effective treatment. Muscarinic receptors (MRs), which serve as key regulators in the parasympathetic nervous system, exhibit significant regulatory functions in non-neural cells. Recent studies suggest that modulating MR activity can elicit anti-carcinogenic effects across various malignancies, stimulating interest in their oncological implications. To investigate this further, we explored the anti-carcinogenic effects of arecaidine but-2-ynyl ester tosylate (ABET), a potential M2 receptor activator, in BC cells using several cellular and molecular assays. METHODS AND

resultsMolecular docking assays were employed to confirm the binding affinity of ABET to M2/M4 receptors. Subsequently, we evaluated the impact of ABET on cell viability, proliferation, clonogenicity, and migration in MDA-MB-231 and MCF-7 BC cell lines. Computational analysis revealed preferential binding of ABET to M2 and M4 receptors. In-vitro experiments demonstrated that ABET markedly inhibits viability, growth, clonogenicity, and migration in BC cells. Notably, ABET induced cell cycle arrest in MDA-MB-231 cells and promoted apoptotic cell death in MCF-7 cells. Furthermore, ABET downregulated key proliferation- and cell cycle-associated genes, including CCND1, CDK6, and MKI67.

conclusionsOur findings underscore ABET as a promising therapeutic candidate for BC treatment, capable of suppressing cell growth, survival, and migration. Additional in-vivo studies are necessary to validate ABET's anti-neoplastic efficacy and evaluate its feasibility as novel therapeutic agent in BC management.