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学科主题临床医学
Matrine, a novel autophagy inhibitor, blocks trafficking and the proteolytic activation of lysosomal proteases
Wang, Zhaohui1,2; Zhang, Jun1; Wang, Yuan1; Xing, Rui3; Yi, Chongqin3; Zhu, Huishan4; Chen, Xianwei1; Guo, Jiao1; Guo, Weixin1; Li, Wenmei3; Wu, Lin1; Lu, Youyong3; Liu, Siqi1
刊名CARCINOGENESIS
2013
DOI10.1093/carcin/bgs295
34期:1页:128-138
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology
研究领域[WOS]Oncology
关键词[WOS]PROGRAMMED CELL-DEATH ; IN-VITRO ; TRIGGERS APOPTOSIS ; CANCER CELLS ; EXPRESSION ; PROLIFERATION ; CROSSTALK ; CASPASE-8 ; PROTEINS ; FUSION
英文摘要

Autophagy has been referred to as a double-edged sword in tumorigenesis and tumor progression. Emerging evidence suggests that pharmacological modulation of autophagy is a promising therapeutic strategy for cancer. However, few autophagy-modulating compounds are currently approved for clinical use in humans. Matrine is a natural compound extracted from traditional Chinese medicine that is widely used for treatment of a variety of diseases without any obvious side effects. Recently, matrine has been reported to induce autophagy and autophagic cell death in cancer cells, although the underlying mechanisms have yet to be elucidated. Here, we systematically examined the autophagic events induced by matrine in SGC7901 cells. The accumulation of autophagic vacuoles in matrine-treated cells was verified by the conversion of microtubule-associated protein light chain 3 as well as confocal and transmission electron microscopy. Furthermore, we demonstrated that matrine blocked autophagic degradation by impairing the activities of lysosomal proteases. Moreover, confocal microscopy and gradient ultracentrifugation revealed that the trafficking processes and proteolytic activation of cathepsins were inhibited by matrine. Using a pH sensor probe, we found elevated pH values in endosomes/lysosomes in response to matrine treatment. Therefore, matrine seems to be a novel autophagy inhibitor that can modulate the maturation process of lysosomal proteases.

语种英语
WOS记录号WOS:000313128600017
项目编号2009CB522204 ; 2004CB518708 ; 2012AA020206
资助机构National Key Basic Research Program of China ; National High Technology Research and Development Program of China, P.R. China
引用统计
被引频次:39[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/67736
专题北京大学临床肿瘤学院_分子肿瘤学研究室
北京大学临床肿瘤学院_高技术实验室
作者单位1.Chinese Acad Sci, Beijing Inst Genom, Beijing 101318, Peoples R China
2.Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China
3.Peking Univ, Lab Mol Oncol, Key Lab Carcinogenesis & Translat Res, Minist Educ,Beijing Canc Hosp Inst,Sch Oncol, Beijing 100142, Peoples R China
4.Beijing Prot Innovat, Beijing 101318, Peoples R China
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Wang, Zhaohui,Zhang, Jun,Wang, Yuan,et al. Matrine, a novel autophagy inhibitor, blocks trafficking and the proteolytic activation of lysosomal proteases[J]. CARCINOGENESIS,2013,34(1):128-138.
APA Wang, Zhaohui.,Zhang, Jun.,Wang, Yuan.,Xing, Rui.,Yi, Chongqin.,...&Liu, Siqi.(2013).Matrine, a novel autophagy inhibitor, blocks trafficking and the proteolytic activation of lysosomal proteases.CARCINOGENESIS,34(1),128-138.
MLA Wang, Zhaohui,et al."Matrine, a novel autophagy inhibitor, blocks trafficking and the proteolytic activation of lysosomal proteases".CARCINOGENESIS 34.1(2013):128-138.
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