Department of Biology, Faculty of Science, Dokuz Eylul University, Izmir, 35390, Turkey.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskisehir, 26470, Turkey.
Chem Biol Interact. 2022 Oct 1;366:110152. doi: 10.1016/j.cbi.2022.110152. Epub 2022 Sep 6.
The bacteriocin, nisin, produced by Lactococcus and Streptococcus species during fermentation, is widely used for bio preservatives in a wide variety of foods. Liver cancer has a high mortality rate and is the fourth leading cause of cancer-related deaths worldwide. Recently, researchers have shown the anti-cancer effects of nisin through in vitro and in vivo studies. This study aimed to investigate the effect of nisin on liver cancer cell lines, which represented two subgroups of the disease model. Nisin exhibited significant growth inhibition and apoptosis in both cell lines, HuH-7, and SNU182. Drug resistance is the main problem in liver cancer and the epithelial-to-mesenchymal transition has a role in the development of drug resistance in hepatocellular carcinoma. The expression of EMT transcription factors ZEB1, SNAI1, and TWIST1 were analyzed depending on nisin treatment, TWIST1 expression was down-regulated after nisin treatment compared to the untreated SNU182 and HuH-7 cell lines. Besides, due to the reported correlation between the overexpression of Frizzled (FZD) proteins, specifically FZD7, in primary hepatocellular carcinomas (HCCs), molecular docking was assessed for Nisin A in the binding site of FZD7. Results confirmed that Nisin A was able to form important hydrogen bonding with key residues. This research not only determined the role of nisin in different liver cancer cell models but it also provided the first result of FZD7 and nisin interaction.
细菌素乳链菌肽由乳球菌和链球菌在发酵过程中产生，被广泛用于各种食品中的生物防腐剂。肝癌死亡率高，是全球癌症相关死亡的第四大原因。最近，研究人员通过体外和体内研究表明了乳链菌肽的抗癌作用。本研究旨在研究乳链菌肽对肝癌细胞系的影响，这些细胞系代表了疾病模型的两个亚组。乳链菌肽对 HuH-7 和 SNU182 两种细胞系均表现出显著的生长抑制和凋亡作用。耐药性是肝癌的主要问题，上皮间质转化在肝癌耐药性的发展中起作用。根据乳链菌肽处理分析 EMT 转录因子 ZEB1、SNAI1 和 TWIST1 的表达，与未处理的 SNU182 和 HuH-7 细胞系相比，TWIST1 的表达在乳链菌肽处理后下调。此外，由于Frizzled (FZD) 蛋白，特别是 FZD7，在原发性肝细胞癌 (HCC) 中的过度表达有报道相关性，因此评估了分子对接在 FZD7 结合位点中 Nisin A 的情况。结果证实 Nisin A 能够与关键残基形成重要氢键。这项研究不仅确定了乳链菌肽在不同肝癌细胞模型中的作用，而且还提供了 FZD7 和乳链菌肽相互作用的第一个结果。
