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非热等离子体通过 mTOR 泛素化诱导抗白血病效应。

Non-Thermal Plasma Induces Antileukemic Effect Through mTOR Ubiquitination.

机构信息

Department of Otolaryngology, Ajou University School of Medicine, Suwon 16499, Korea.

Oncoprotein Modification and Regulation Research Center, Ajou University, Suwon 16499, Korea.

出版信息

Cells. 2020 Mar 2;9(3):595. doi: 10.3390/cells9030595.

DOI:10.3390/cells9030595
PMID:32131492
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7140413/
Abstract

Non-thermal plasma (NTP) has been studied as a novel therapeutic tool for cancer that does not damage healthy cells. In this study, we show that NTP-treated solutions (NTS) can induce death in various leukemia cells through mechanistic target of rapamycin (mTOR) ubiquitination. Previously, we manufactured and demonstrated the efficacy of NTS in solid cancers. NTS did not exhibit any deleterious side effects, such as acute death or weight loss in nude mice. In the present study, NTS induced cell death in myeloid leukemia cells, including acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). We found that mTOR was downregulated in NTS-treated cells via the ubiquitin-proteasome system (UPS). We also identified 'really interesting new gene' finger protein 126 (RNF126) as a novel binding protein for mTOR through protein arrays and determined the role of E3 ligase in NTS-induced mTOR ubiquitination. NTS-derived reactive oxygen species (ROS) affected RNF126 expression and lysosomal dysfunction. These findings suggest that NTS has potential antileukemic effects through RNF126-mediated mTOR ubiquitination with no deleterious side effects. Thus, NTS may represent a new therapeutic method for chemotherapy-resistant leukemia.

摘要

非热等离子体 (NTP) 已被研究为一种新型的癌症治疗工具，它不会损伤健康细胞。在这项研究中，我们表明 NTP 处理的溶液 (NTS) 通过雷帕霉素靶蛋白 (mTOR) 泛素化可以诱导各种白血病细胞死亡。此前，我们制造并证明了 NTS 在实体瘤中的疗效。NTS 没有表现出任何有害的副作用，例如裸鼠的急性死亡或体重减轻。在本研究中，NTS 诱导了髓系白血病细胞，包括急性髓系白血病 (AML) 和慢性髓系白血病 (CML) 的死亡。我们发现 mTOR 通过泛素蛋白酶体系统 (UPS) 在 NTS 处理的细胞中下调。我们还通过蛋白质阵列鉴定出“真的很有趣的新基因”手指蛋白 126 (RNF126) 是 mTOR 的一种新型结合蛋白，并确定了 E3 连接酶在 NTS 诱导的 mTOR 泛素化中的作用。NTS 衍生的活性氧 (ROS) 影响 RNF126 的表达和溶酶体功能障碍。这些发现表明，NTS 通过 RNF126 介导的 mTOR 泛素化具有潜在的抗白血病作用，而没有有害的副作用。因此，NTS 可能代表一种治疗化疗耐药性白血病的新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e8a/7140413/8638e33316bd/cells-09-00595-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e8a/7140413/47206e37f96d/cells-09-00595-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e8a/7140413/8d37054529fa/cells-09-00595-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e8a/7140413/1bc9876b1eaf/cells-09-00595-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e8a/7140413/86f711fe4421/cells-09-00595-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e8a/7140413/af2857383c96/cells-09-00595-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e8a/7140413/8638e33316bd/cells-09-00595-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e8a/7140413/47206e37f96d/cells-09-00595-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e8a/7140413/8d37054529fa/cells-09-00595-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e8a/7140413/1bc9876b1eaf/cells-09-00595-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e8a/7140413/86f711fe4421/cells-09-00595-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e8a/7140413/af2857383c96/cells-09-00595-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e8a/7140413/8638e33316bd/cells-09-00595-g006.jpg

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