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学科主题: 基础医学
题名:
Autophagy induced by suberoylanilide hydroxamic acid in Hela S3 cells involves inhibition of protein kinase B and up-regulation of Beclin 1
作者: Cao, Qi1; Yu, Chuanfei2; Xue, Ruiqi1; Hsueh, Wei3; Pan, Peng1; Chen, Zhengshan1; Wang, Shenglan1; McNutt, Michael1; Gu, Jiang1
关键词: SAHA ; autophagy ; LC3 ; PI3K-Akt-mTOR ; Beclin 1
刊名: INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
发表日期: 2008
DOI: 10.1016/j.biocel.2007.07.020
卷: 40, 期:2, 页:272-283
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Cell Biology
研究领域[WOS]: Biochemistry & Molecular Biology ; Cell Biology
关键词[WOS]: HISTONE-DEACETYLASE INHIBITORS ; MALIGNANT GLIOMA-CELLS ; CANCER-CELLS ; DEATH ; APOPTOSIS ; SENESCENCE ; PATHWAYS ; SURVIVAL ; GROWTH ; MACROAUTOPHAGY
英文摘要:

Histone deacetylase inhibitors are promising chemotherapeutic agents and some are in clinical trials. Several molecular mechanisms have been invoked to describe their effects on cancer cells in vivo and in vitro. Autophagy has been observed in response to several anticancer reagents and has been demonstrated to be responsible for cell death. However, the exact mechanism of this phenomenon is still not clear. Here we demonstrated that suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, induces nonapoptotic cell death with several specific features characteristic of autophagy in Hela S3 cells. Suberoylanilide hydroxamic acid inhibits the activity of the mammalian target of rapamycin, a negative regulator of macroautophagy which induces the formation of autophagosomes in a Beclin 1- and autophagy-related 7-dependent manner. This process is mediated by Akt and tuberous sclerosis 2 as is demonstrated by inhibition by continuous active Akt plasmid transfection and RNA interference of tuberous sclerosis 2. Our data provide the first evidence that suberoylanilide hydroxamic acid induces autophagy in Hela S3 cells through interference with the mammalian target of rapamycin signaling pathway. These findings suggest that suberoylanilide hydroxamic acid may induce autophagic cancer cell death via its specific pathway, and invite further investigation into the detailed mechanism of this pathway to explore this compound′s full potential as a chemotherapeutic agent. (c) 2007 Elsevier Ltd. All rights reserved.

语种: 英语
WOS记录号: WOS:000252061800012
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/61582
Appears in Collections:基础医学院_病理学系_期刊论文

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作者单位: 1.Peking Univ, Sch Basic Med Sci, Dept Pathol, Beijing 100083, Peoples R China
2.Peking Univ, Sch Basic Med Sci, Lab Med Immunol, Beijing 100083, Peoples R China
3.Northwestern Univ, Feinberg Sch Med, Dept Pathol, Chicago, IL 60611 USA

Recommended Citation:
Cao, Qi,Yu, Chuanfei,Xue, Ruiqi,et al. Autophagy induced by suberoylanilide hydroxamic acid in Hela S3 cells involves inhibition of protein kinase B and up-regulation of Beclin 1[J]. INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY,2008,40(2):272-283.
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