Matrine induces autophagic cell death by triggering ROS/AMPK/mTOR axis and apoptosis in multiple myeloma

doi:10.1016/j.biopha.2024.116738

科研成果详情

题名	Matrine induces autophagic cell death by triggering ROS/AMPK/mTOR axis and apoptosis in multiple myeloma
作者	Li, Xue1,2,3; Zhou, Jifan1,2; Ling, Yixin1,2,3; Tan, Yicheng2,3,4; Zhang, Jialing 2,3,5; Wang, Xiaofang1,2,3; Li, Fanfan1,2,3; Jiang, Songfu1,2,3; Zhang, Shenghui1,2,3,4; Yu, Kang1,2,3; Han, Yixiang2,3,5
发表日期	2024-05-16
发表期刊	Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 影响因子和分区
语种	英语
原始文献类型	Journal Article
关键词	Apoptosis Autophagy Matrine Multiple myeloma Reactive oxygen species
其他关键词	STRESS ; CANCER
摘要	Despite significant advancements in multiple myeloma (MM) treatment in recent years, most patients will eventually develop resistance or experience relapse. Matrine, a primary active compound of traditional Chinese medicinal herb Sophora flavescens Ait, has been found to have anti-tumor properties in various types of malignant tumors. Whether autophagy plays a crucial role in the anti-MM effect of matrine remain unknown. Herein, we found that matrine could trigger apoptosis and cell cycle arrest, and meanwhile induce autophagy in MM cells in vitro. We further ascertained the role of autophagy by using ATG5 siRNA or the autophagy inhibitor spautin-1, which partially reversed matrine's inhibitory effect on MM cells. Conversely, the combination of matrine with the autophagy inducer rapamycin enhanced their anti-tumor activity. These findings suggest that autophagy induced by matrine can lead to cell death in MM cells. Further mechanism investigation revealed that matrine treatment increased the levels of reactive oxygen species (ROS) and AMPKα1 phosphorylation and decreased the phosphorylation of mTOR in MM cells. Additionally, co-treatment with AMPKα1 siRNA or the ROS scavenger N-acetyl-1-cysteine weakened the increase in autophagy that was induced by matrine. Finally, we demonstrated a synergistic inhibitory effect of matrine and rapamycin against MM in a xenograft mouse model. Collectively, our findings provided novel insights into the anti-MM efficacy of matrine and suggest that matrine induces autophagy by triggering ROS/AMPK/mTOR axis in MM cells, and combinatorial treatment of matrine and rapamycin may be a promising therapeutic strategy against MM.
资助项目	Zhejiang Provincial Traditional Chinese Medicine Science and Technology Program[2023ZL508];National Natural Science Foundation of China[82072354];
出版者	Elsevier Masson s.r.l.
ISSN	0753-3322
EISSN	1950-6007
卷号	175
DOI	10.1016/j.biopha.2024.116738
页数	12
WOS类目	Medicine, Research & Experimental ; Pharmacology & Pharmacy
WOS研究方向	Research & Experimental Medicine ; Pharmacology & Pharmacy
WOS记录号	WOS:001291651800001
收录类别	PUBMED ; SCOPUS ; SCIE
URL	查看原文
PubMed ID	38759291
SCOPUSEID	2-s2.0-85192870575
通讯作者地址	[Zhang, Shenghui]Laboratory Animal Center,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325015,China ; [Yu, Kang]Department of Hematology,Wenzhou Key Laboratory of Hematology,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325015,China ; [Han, Yixiang]Central Laboratory,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325015,China
Scopus学科分类	Pharmacology
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/212904
专题	附属第一医院第一临床医学院（信息与工程学院）、附属第一医院实验动物中心
通讯作者	Zhang, Shenghui; Yu, Kang; Han, Yixiang
作者单位	1.Department of Hematology,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,China; 2.Institute of Hematology,Wenzhou Medical University,Zhejiang,Wenzhou,China; 3.Wenzhou Key Laboratory of Hematology,Zhejiang,Wenzhou,China; 4.Laboratory Animal Center,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,China; 5.Central Laboratory,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,China
第一作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院; 温州医科大学
通讯作者单位	附属第一医院; 实验动物中心; 第一临床医学院（信息与工程学院）、附属第一医院
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Li, Xue,Zhou, Jifan,Ling, Yixin,et al. Matrine induces autophagic cell death by triggering ROS/AMPK/mTOR axis and apoptosis in multiple myeloma[J]. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie,2024,175.
APA	Li, Xue., Zhou, Jifan., Ling, Yixin., Tan, Yicheng., Zhang, Jialing., ... & Han, Yixiang. (2024). Matrine induces autophagic cell death by triggering ROS/AMPK/mTOR axis and apoptosis in multiple myeloma. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 175.
MLA	Li, Xue,et al."Matrine induces autophagic cell death by triggering ROS/AMPK/mTOR axis and apoptosis in multiple myeloma".Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 175(2024).