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学科主题: 临床医学
题名:
Matrine, a novel autophagy inhibitor, blocks trafficking and the proteolytic activation of lysosomal proteases
作者: 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
发表日期: 2013
DOI: 10.1093/carcin/bgs295
卷: 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
所属项目编号: 2009CB522204 ; 2004CB518708 ; 2012AA020206
项目资助者: National Key Basic Research Program of China ; National High Technology Research and Development Program of China, P.R. China
WOS记录号: WOS:000313128600017
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/67736
Appears in Collections:北京大学临床肿瘤学院_分子肿瘤学研究室_期刊论文

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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

Recommended Citation:
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.
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