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. 2023 Oct 10;24(20):15053. doi: 10.3390/ijms242015053.
The gut microbiota undergoes metabolic processes to produce by-products (gut metabolites), which play a vital role in the overall maintenance of health and prevention of disease within the body. However, the use of gut metabolites as anticancer agents and their molecular mechanisms of action are largely unknown. Therefore, this study evaluated the anti-proliferative effects of three key gut microbial metabolites-sodium butyrate, inosine, and nisin, against MCF7 and MDA-MB-231 breast adenocarcinoma cell lines. To determine the potential mechanistic action of these gut metabolites, flow cytometric assessments of apoptotic potential, reactive oxygen species (ROS) production measurements and proteomics analyses were performed. Sodium butyrate exhibited promising cytotoxicity, with IC values of 5.23 mM and 5.06 mM against MCF7 and MDA-MB-231 cells, respectively. All three metabolites were found to induce apoptotic cell death and inhibit the production of ROS in both cell lines. Nisin and inosine indicated a potential activation of cell cycle processes. Sodium butyrate indicated the possible initiation of signal transduction processes and cellular responses to stimuli. Further investigations are necessary to ascertain the effective therapeutic dose of these metabolites, and future research on patient-derived tumour spheroids will provide insights into the potential use of these gut metabolites in cancer therapy.
肠道微生物群通过代谢过程产生代谢产物（肠道代谢物），这些代谢产物在体内整体维持健康和预防疾病方面发挥着至关重要的作用。然而，肠道代谢物作为抗癌剂的用途及其作用的分子机制在很大程度上尚不清楚。因此，本研究评估了三种关键的肠道微生物代谢物——丁酸钠、肌苷和乳链菌肽——对 MCF7 和 MDA-MB-231 乳腺癌腺癌细胞系的抗增殖作用。为了确定这些肠道代谢物的潜在作用机制，进行了流式细胞术评估凋亡潜力、活性氧 (ROS) 产生测量和蛋白质组学分析。丁酸钠表现出有前景的细胞毒性，对 MCF7 和 MDA-MB-231 细胞的 IC 值分别为 5.23 mM 和 5.06 mM。所有三种代谢物均诱导两种细胞系的细胞凋亡和抑制 ROS 的产生。乳链菌肽和肌苷表明细胞周期过程的潜在激活。丁酸钠表明可能启动了信号转导过程和细胞对刺激的反应。需要进一步研究以确定这些代谢物的有效治疗剂量，并且对患者来源的肿瘤球体的未来研究将为这些肠道代谢物在癌症治疗中的潜在用途提供深入了解。
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