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新型曲霉代谢产物对人前列腺癌细胞的作用及其对幽门螺杆菌和志贺毒素产生性大肠杆菌的抑制作用。

Novel metabolites from Trichoderma atroviride against human prostate cancer cells and their inhibitory effect on Helicobacter pylori and Shigella toxin producing Escherichia coli.

机构信息

Department of Medical Biotechnology, College of Biomedical Sciences, Kangwon National University, Chuncheon 24341, South Korea.

College of Pharmacy, Kangwon National University, Chuncheon 24341, South Korea.

出版信息

Microb Pathog. 2019 Jan;126:19-26. doi: 10.1016/j.micpath.2018.10.011. Epub 2018 Oct 10.

Abstract

The present study aimed to purify and identify the metabolites from T. atroviride using high-performance liquid chromatography (HPLC) and H and C nuclear magnetic resonance spectrometer (NMR) followed by analyzing their toxicological, antibacterial and anticancer properties. This work identified two metabolites - TM1 and TM2. TM1 was in two forms: (i) 1, 3-dione-5, 5-dimethylcyclohexane; and, (ii) 2-enone-3hydroxy -5,5-dimethylcylohex, while TM2 was 4H-1,3-dioxin-4-one-2,3,6-trimethyl. These metabolites did not exhibit any irritant or allergic reaction as revealed by HET- CAM test. TM2 significantly inhibited the growth of H. pylori and Shigella toxin producing Escherichia coli (STEC) as evident by in vitro and microscopic observations of bacterial cell death. TM2 also induced the cell death and cytotoxicity, as revealed by cell viability test and western blot analysis. According to microscopic, flow cytometer and western blot analysis, TM2 treated cells displayed higher ROS, cell death, and apoptosis-related protein expression than TM1 and control. This study concluded that TM2 derived from T. atroviride was a potential therapeutic agent for anti-prostate cancer and antibiotic agent against MDR- H. pylori and STEC and it is also recommended to carry out further in vivo animal model experiments with improved stability of the metabolites for future pharmaceutical trails.

摘要

本研究旨在通过高效液相色谱(HPLC)和 H 和 C 核磁共振谱仪(NMR)对 T. atroviride 的代谢产物进行纯化和鉴定,并分析其毒理学、抗菌和抗癌特性。这项工作鉴定了两种代谢产物 - TM1 和 TM2。TM1 有两种形式:(i)1,3-二酮-5,5-二甲基环己烷;和,(ii)2-烯酮-3 羟基-5,5-二甲基环己烷,而 TM2 是 4H-1,3-二恶英-4-酮-2,3,6-三甲基。这些代谢产物在 HET-CAM 测试中没有显示出任何刺激性或过敏反应。TM2 通过体外和细菌细胞死亡的显微镜观察,显著抑制了 H. pylori 和产志贺毒素的大肠杆菌(STEC)的生长。TM2 还通过细胞活力试验和 Western blot 分析诱导细胞死亡和细胞毒性。根据显微镜、流式细胞仪和 Western blot 分析,与 TM1 和对照相比,TM2 处理的细胞显示出更高的 ROS、细胞死亡和与凋亡相关的蛋白表达。这项研究得出结论,TM2 来源于 T. atroviride,是一种潜在的抗前列腺癌治疗剂和抗生素,用于对抗多药耐药性 H. pylori 和 STEC,还建议进一步进行具有更好代谢产物稳定性的体内动物模型实验,为未来的药物试验做好准备。

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