In Silico and in vitro Characterization of Lactobacillus acidophilus 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 andbreast cancer (BC). Objectives: This study investigated the anticancer properties of bacteriocins produced byLactobacillus acidophilus, specificallytheir 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 moleculardynamics (MD) simulations, this research elucidated the dynamic interactions and binding strengths of four distinctbacteriocins - Acidocin A, Acidocin B, Acidocin 8912, and Acidocin J1132 beta - with the ROR-1 receptor. This observation wassubstantiated by consistent hydrogen bond formation and low root mean square deviation (RMSD) values throughout thesimulation period. Furthermore, the biological activity of crude acidocins was evaluated on the ROR-1-Src signaling axis inMichigan 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 interventiondirected at ROR-1 in BC. Furthermore, the synergistic application of molecular docking, MD simulations, and molecularmechanics/Poisson-Boltzmann surface area (MM/PBSA) free energy calculations yielded a thorough elucidation of theunderlying interaction mechanisms. The assessment of protein expression levels indicated a significant downregulation of theROR-1-Src signaling pathway following treatment with Acidocins. Conclusions: This research highlights the potential of bacteriocins in cancer treatment and adds to evidence linking themicrobiota to cancer, establishing new pathways for anticancer therapies from microbial sources.