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A novel lonidamine derivative targeting mitochondria to eliminate cancer stem cells by blocking glutamine metabolism

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收录情况： ◇ SCIE

作者：
Wang Qiang[1] * ; Li Shiyou[1] * ; Xu Chen[1] ; Hua Ao[1] ; Wang Chong[1] ; Xiong Yuxuan[1] ; Deng Qingyuan[1] ; Chen Xiang[1] ; Yang Tian[1] ; Wan Jiangling[1] ; Ding Ze-Yang[2] ; Zhang Bi-Xiang[2] ; Yang Xiangliang[1,3,4,5,7] ; Li Zifu[1,3,4,6,7,*1] ;
单位： [1]National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, PR China [2]Hepatic Surgery Center and Hubei Key Laboratory of Hepato-Pancreatic-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China [3]Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, PR China [4]Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medical, Huazhong University of Science and Technology, Wuhan 430074, PR China [5]GBA Research Innovation Institute for Nanotechnology, Guangdong 510530, PR China [6]Hubei Engineering Research Center for Biomaterials and Medical Protective Materials, Huazhong University of Science and Technology, Wuhan 430074, PR China [7]Hubei Bioinformatics and Molecular Imaging Key Laboratory, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074,
出处：
DOI： 10.1016/j.phrs.2023.106740
ISSN：

关键词： HYL001 Cancer stem cells Mitochondrial targeting Glutamine metabolism

摘要：
Cancer stem cells (CSCs) have been blamed as the main culprit of tumor initiation, progression, metastasis, chemoresistance, and recurrence. However, few anti-CSCs agents have achieved clinical success so far. Here we report a novel derivative of lonidamine (LND), namely HYL001, which selectively and potently inhibits CSCs by targeting mitochondria, with 380-fold and 340-fold lower IC50 values against breast cancer stem cells (BCSCs) and hepatocellular carcinoma stem cells (HCSCs), respectively, compared to LND. Mechanistically, we reveal that HYL001 downregulates glutaminase (GLS) expression to block glutamine metabolism, blunt tricarboxylic acid cycle, and amplify mitochondrial oxidative stress, leading to apoptotic cell death. Therefore, HYL001 displays significant antitumor activity in vivo, both as a single agent and combined with paclitaxel. Furthermore, HYL001 represses CSCs of fresh tumor tissues derived from liver cancer patients. This study provides critical implications for CSCs biology and development of potent anti-CSCs drugs.Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

基金：
National Research and Development Program of China (2020YFA0211200, 2020YFA0710700, and 2018YFA0208900), the National Science Foundation of China (31972927, 82172757), the Scientific Research Foundation of Huazhong University of Science and Technology (3004170130), the Program for HUST Academic Frontier Youth Team (2018QYTD01), and the HCP Program for HUST.
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外文
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中科院(CAS)分区：
出版当年[2022]版：
大类 | 1 区 医学
小类 | 1 区 药学
最新[2025]版：
大类 | 2 区 医学
小类 | 1 区 药学
JCR分区：
出版当年[2021]版：
Q1 PHARMACOLOGY & PHARMACY
最新[2023]版：
Q1 PHARMACOLOGY & PHARMACY

影响因子： 最新[2023版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

第一作者：
第一作者单位： [1]National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, PR China
共同第一作者：
通讯作者：
通讯机构： [1]National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, PR China [3]Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, PR China [4]Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medical, Huazhong University of Science and Technology, Wuhan 430074, PR China [6]Hubei Engineering Research Center for Biomaterials and Medical Protective Materials, Huazhong University of Science and Technology, Wuhan 430074, PR China [7]Hubei Bioinformatics and Molecular Imaging Key Laboratory, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, [*1]National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, PR China.
推荐引用方式(GB/T 7714)：
Wang Qiang,Li Shiyou,Xu Chen,et al.A novel lonidamine derivative targeting mitochondria to eliminate cancer stem cells by blocking glutamine metabolism[J].PHARMACOLOGICAL RESEARCH.2023,190:doi:10.1016/j.phrs.2023.106740.
APA：
Wang Qiang,Li Shiyou,Xu Chen,Hua Ao,Wang Chong...&Li Zifu.(2023).A novel lonidamine derivative targeting mitochondria to eliminate cancer stem cells by blocking glutamine metabolism.PHARMACOLOGICAL RESEARCH,190,
MLA：
Wang Qiang,et al."A novel lonidamine derivative targeting mitochondria to eliminate cancer stem cells by blocking glutamine metabolism".PHARMACOLOGICAL RESEARCH 190.(2023)

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