Gut microbial postbiotics as potential therapeutics for lymphoma: Proteomics Insights of the synergistic effects of Nisin and Urolithin B against human lymphoma cells

Lymphoma remains a substantial global health concern, necessitating innovative therapeutic strategies. The emerging role of gut microbiota-derived metabolites, known as postbiotics, offers promising avenues for cancer treatment. This study evaluated the antiproliferative activities of various postbiotics, including Nisin (N) and urolithin B (UB), and their combinations against the human lymphoma cell line HKB-11. Systematically, the antiproliferative effects and underlying mechanisms were characterised using Alamar Blue assays, combination index (CI) analyses, ROS measurements, flow cytometry, and bottom-up proteomics analyses of combined and mono-treatments. Nisin and UB demonstrated significant antiproliferative activity with IC50 values of 1467 µM and 87.56 µM, respectively. Among other ratios, their combination at a ratio of 4:6 exhibited potent synergy (CI =0.09 at IC95), notably enhancing apoptosis (p < 0.0001) and modulating ROS levels. Proteomics analyses identified key protein alterations involved in lipid metabolism, mitochondrial function, cell cycle progression, and apoptosis.