Al-Khazaleh Ahmad K, Alsherbiny Muhammad A, Münch Gerald, Chang Dennis, Bhuyan Deep Jyoti
NICM Health Research Institute, Western Sydney University, Penrith, NSW 2751, Australia.
Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
Int J Mol Sci. 2025 Jul 16;26(14):6829. doi: 10.3390/ijms26146829.
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 IC values of 1467 µM and 87.56 µM, respectively. Importantly, their combination at a 4:6 ratio demonstrated strong synergy (CI = 0.09 at IC), significantly enhancing apoptosis ( ≤ 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 (LogFC = 2.07) and downregulation of CDK4 (LogFC = -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.
淋巴瘤仍然是一个重大的全球健康负担，凸显了对新型治疗策略的迫切需求。微生物组研究的最新进展已将肠道微生物群衍生的代谢产物（即后生元）确定为癌症治疗中很有前景的候选物质。本研究调查了两种后生元——乳酸链球菌素（N）和尿石素B（UB）单独及联合使用对人淋巴瘤细胞系HKB - 11 的抗增殖作用及其作用机制。此外，本研究采用了包括阿拉玛蓝检测、联合指数（CI）分析、流式细胞术、活性氧（ROS）定量和自下而上蛋白质组学在内的综合实验方法，评估了细胞毒性功效和潜在分子途径。N和UB显示出显著的抗增殖作用，IC值分别为1467 μM和87.56 μM。重要的是，它们以4:6的比例联合使用表现出很强协同作用（在IC时CI = 0.09），显著增强了细胞凋亡（≤0.0001）并调节了氧化应激。蛋白质组分析揭示了与脂质代谢、线粒体功能、细胞周期控制和细胞凋亡相关关键蛋白的显著调控变化，包括COX6C上调（LogFC = 2.07）和CDK4下调（LogFC = -1.26）。这些发现提供了作用机制方面的见解，并强调了后生元在淋巴瘤治疗中的转化潜力。有必要进行进一步的临床前和临床研究，以探索它们在治疗方案中的作用。
