In Silico and in vitro Characterization of <i>Lactobacillus acidophilus</i> Bacteriocins as ROR-1-Targeted Therapeutics in Breast Cancer

Abstract

Background: The human microbiota plays a crucial role in maintaining host health and is involved in various illnesses, including cancer. The intestinal microbiota has been identified as a factor in the development of colorectal carcinoma and breast cancer (BC). Objectives: This study investigated the anticancer properties of bacteriocins produced by Lactobacillus acidophilus, specifically their interaction with receptor tyrosine kinase-like orphan receptor 1 (ROR-1), a protein involved in aggressive BC subtypes. Methods: Employing sophisticated computational methodologies, encompassing molecular docking and molecular dynamics (MD) simulations, this research elucidated the dynamic interactions and binding strengths of four distinct bacteriocins — Acidocin A, Acidocin B, Acidocin 8912, and Acidocin J1132β — with the ROR-1 receptor. This observation was substantiated by consistent hydrogen bond formation and low root mean square deviation (RMSD) values throughout the simulation period. Furthermore, the biological activity of crude acidocins was evaluated on the ROR-1-Src signaling axis in Michigan Cancer Foundation-7 (MCF-7) and MDA-MB-231 cell lines utilizing Western blot analysis. Results: The findings of this research demonstrate that Acidocin A exhibits promise as a prospective therapeutic intervention directed at ROR-1 in BC. Furthermore, the synergistic application of molecular docking, MD simulations, and molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) free energy calculations yielded a thorough elucidation of the underlying interaction mechanisms. The assessment of protein expression levels indicated a significant downregulation of the ROR-1-Src signaling pathway following treatment with Acidocins. Conclusions: This research highlights the potential of bacteriocins in cancer treatment and adds to evidence linking the microbiota to cancer, establishing new pathways for anticancer therapies from microbial sources.