Necroptosis signaling and mitochondrial dysfunction cross-talking facilitate cell death mediated by chelerythrine in glioma

doi:10.1016/j.freeradbiomed.2023.03.021

科研成果详情

题名	Necroptosis signaling and mitochondrial dysfunction cross-talking facilitate cell death mediated by chelerythrine in glioma
作者	Wang, Peng1; Zheng, Shi-Yi 1; Jiang, Ruo-Lin1; Wu, Hao-Di1; Li, Yong-Ang 3; Lu, Jiang-Long2; Xiong, Ye2; Han, Bo 4; Lin, Li1
发表日期	2023-06
发表期刊	Free radical biology & medicine 影响因子和分区
语种	英语
原始文献类型	Journal Article
关键词	Calcium Chelerythrine Glioblastoma Mitochondrial dysfunction Necroptosis
其他关键词	MECHANISMS ; FISSION ; ACTIVATION ; THERAPY
摘要	Glioma is the most common primary malignant brain tumor with poor survival and limited therapeutic options. Chelerythrine (CHE), a natural benzophenanthridine alkaloid, has been reported to exhibit the anti-tumor effects in a variety of cancer cells. However, the molecular target and the signaling process of CHE in glioma remain elusive. Here we investigated the underlying mechanisms of CHE in glioma cell lines and glioma xenograft mice model. Our results found that CHE-induced cell death is associated with RIP1/RIP3-dependent necroptosis rather than apoptotic cell death in glioma cells at the early time. Mechanism investigation revealed the cross-talking between necroptosis and mitochondria dysfunction that CHE triggered generation of mitochondrial ROS, mitochondrial depolarization, reduction of ATP level and mitochondrial fragmentation, which was the important trigger for RIP1-dependent necroptosis activation. Meanwhile, PINK1 and parkin-dependent mitophagy promoted clearance of impaired mitochondria in CHE-incubated glioma cells, and inhibition of mitophagy with CQ selectively enhanced CHE-induced necroptosis. Furthermore, early cytosolic calcium from the influx of extracellular Ca2+ induced by CHE acted as important "priming signals" for impairment of mitochondrial dysfunction and necroptosis. Suppression of mitochondrial ROS contributed to interrupting positive feedback between mitochondrial damage and RIPK1/RIPK3 necrosome. Lastly, subcutaneous tumor growth in U87 xenograft was suppressed by CHE without significant body weight loss and multi-organ toxicities. In summary, the present study helped to elucidate necroptosis was induced by CHE via mtROS-mediated formation of the RIP1-RIP3-Drp1 complex that promoted Drp1 mitochondrial translocation to enhance necroptosis. Our findings indicated that CHE could potentially be further developed as a novel therapeutic strategy for treatment of glioma
资助项目	National Natural Science Foundation of China [82003793]; Medical Health Science and Technology Project of Zhejiang Provincial Health Commission [2021KY201, 2023RC307]; Wenzhou Science and Tech- nology Plan Project [Y2020183]; Zhejiang Province Xinmiao Talent Program [2022R413C076]
出版者	ELSEVIER SCIENCE INC
ISSN	0891-5849
EISSN	1873-4596
卷号	202 页码:76-96
DOI	10.1016/j.freeradbiomed.2023.03.021
页数	21
WOS类目	Biochemistry & Molecular Biology ; Endocrinology & Metabolism
WOS研究方向	Biochemistry & Molecular Biology ; Endocrinology & Metabolism
WOS记录号	WOS:000968004300001
收录类别	PUBMED ; SCIE ; SCOPUS
在线发表日期	2023-04
URL	查看原文
PubMed ID	36997101
SCOPUSEID	2-s2.0-85151404541
通讯作者地址	[Lin, Li]School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou,325035,China ; [Han, Bo]Guang'anmen Hospital,China Academy of Chinese Medical Sciences,Beijing,100053,China ; [Xiong, Ye]Department of Neurosurgery,First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325035,China
Scopus学科分类	Biochemistry;Physiology (medical)
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/174194
专题	药学院（分析测试中心）附属第一医院_神经外科
通讯作者	Xiong, Ye; Han, Bo; Lin, Li
作者单位	1.School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou,325035,China; 2.Department of Neurosurgery,First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325035,China; 3.Department of Neurosurgery,The First People's Hospital of Wenling,Wenling,317500,China; 4.Guang'anmen Hospital,China Academy of Chinese Medical Sciences,Beijing,100053,China
第一作者单位	药学院（分析测试中心）
通讯作者单位	药学院（分析测试中心）; 附属第一医院
第一作者的第一单位	药学院（分析测试中心）
推荐引用方式 GB/T 7714	Wang, Peng,Zheng, Shi-Yi,Jiang, Ruo-Lin,et al. Necroptosis signaling and mitochondrial dysfunction cross-talking facilitate cell death mediated by chelerythrine in glioma[J]. Free radical biology & medicine,2023,202:76-96.
APA	Wang, Peng., Zheng, Shi-Yi., Jiang, Ruo-Lin., Wu, Hao-Di., Li, Yong-Ang., ... & Lin, Li. (2023). Necroptosis signaling and mitochondrial dysfunction cross-talking facilitate cell death mediated by chelerythrine in glioma. Free radical biology & medicine, 202, 76-96.
MLA	Wang, Peng,et al."Necroptosis signaling and mitochondrial dysfunction cross-talking facilitate cell death mediated by chelerythrine in glioma".Free radical biology & medicine 202(2023):76-96.