Gut Microbial Postbiotics as Potential Therapeutics for Lymphoma: Proteomics Insights of the Synergistic Effects of Nisin and Urolithin B Against Human Lymphoma Cells

Al-Khazaleh, Ahmad K. and Alsherbiny, Muhammad A. and Münch, Gerald and Chang, Dennis and Bhuyan, Deep Jyoti (2025) Gut Microbial Postbiotics as Potential Therapeutics for Lymphoma: Proteomics Insights of the Synergistic Effects of Nisin and Urolithin B Against Human Lymphoma Cells. International Journal of Molecular Sciences, 26 (14). p. 6829. ISSN 1422-0067

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Link to published document: https://doi.org/10.3390/ijms26146829

Abstract

Lymphoma continues to pose a significant global health burden, highlighting the urgent need for novel therapeutic strategies. Recent advances in microbiome research have identified gut-microbiota-derived metabolites, or postbiotics, as promising candidates in cancer therapy. This study investigates the antiproliferative and mechanistic effects of two postbiotics, Nisin (N) and Urolithin B (UB), individually and in combination, against the human lymphoma cell line HKB-11. Moreover, this study evaluated cytotoxic efficacy and underlying molecular pathways using a comprehensive experimental approach, including the Alamar Blue assay, combination index (CI) analysis, flow cytometry, reactive oxygen species (ROS) quantification, and bottom-up proteomics. N and UB displayed notable antiproliferative effects, with IC50 values of 1467 µM and 87.56 µM, respectively. Importantly, their combination at a 4:6 ratio demonstrated strong synergy (CI = 0.09 at IC95), significantly enhancing apoptosis (p ≤ 0.0001) and modulating oxidative stress. Proteomic profiling revealed significant regulation of key proteins related to lipid metabolism, mitochondrial function, cell cycle control, and apoptosis, including upregulation of COX6C (Log2FC = 2.07) and downregulation of CDK4 (Log2FC = −1.26). These findings provide mechanistic insights and underscore the translational potential of postbiotics in lymphoma treatment. Further preclinical and clinical investigations are warranted to explore their role in therapeutic regimens.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Depositing User: Repository Administrator
Date Deposited: 03 Nov 2025 02:24
Last Modified: 03 Nov 2025 02:24
URI: http://eprints.victorchang.edu.au/id/eprint/1733

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