Investigating the Cellular Responses to Combined Nisin and Urolithin B Treatment (7:3) in HKB-11 Lymphoma Cells

Al-Khazaleh, Ahmad K. and Alsherbiny, Muhammad A. and Chang, Dennis and Münch, Gerald and Bhuyan, Deep Jyoti (2025) Investigating the Cellular Responses to Combined Nisin and Urolithin B Treatment (7:3) in HKB-11 Lymphoma Cells. International Journal of Molecular Sciences, 26 (15). p. 7369. ISSN 1422-0067

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Link to published document: https://doi.org/10.3390/ijms26157369

Abstract

Lymphoma continues to pose a serious challenge to global health, underscoring the urgent need for new therapeutic strategies. Recently, the gut microbiome has been shown to play a potential role in regulating immune responses and influencing cancer progression. However, its molecular mechanisms of action in lymphoma remain poorly understood. This study investigates the antiproliferative and apoptotic activities of gut microbiota-derived metabolites, specifically nisin (N) and urolithin B (UB), individually and in combination 7:3 (5750 μM), against the human lymphoma cell line HKB-11. Comprehensive evaluations were performed using Alamar Blue viability assays, combination index (CI) analyses, reactive oxygen species (ROS) quantification, flow cytometry for apoptosis detection, and advanced bottom-up proteomics analyses. N and UB exhibited potent antiproliferative activity, with the 7:3 combination demonstrating strong synergistic effects (CI < 1), significantly enhancing apoptosis (p < 0.01) and ROS production (p < 0.0001) compared to the untreated control. Proteomics analyses revealed substantial alterations in proteins crucial to ribosomal biogenesis, mitochondrial function, cell cycle control, and apoptosis regulation, including a marked downregulation of ribosomal proteins (RPS27; Log2FC = −3.47) and UBE2N (Log2FC = −0.60). These findings highlight the potential of N and UB combinations as a novel and practical therapeutic approach for lymphoma treatment, warranting further in vivo exploration and clinical validation.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Depositing User: Repository Administrator
Date Deposited: 03 Nov 2025 02:22
Last Modified: 03 Nov 2025 02:22
URI: http://eprints.victorchang.edu.au/id/eprint/1732

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