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学科主题: 口腔医学
题名:
Synergistic induction of apoptosis by HMG-CoA reductase inhibitor and histone deacetylases inhibitor in HeLa cells
作者: Gan, Yehua; Wang, Jian; Coselli, Joseph; Wang, Xing Li
关键词: HMG-CoA ; statin ; TSA ; apoptosis ; RhoA
刊名: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
发表日期: 2008-01-11
DOI: 10.1016/j.bbrc.2007.11.002
卷: 365, 期:2, 页:386-392
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Biophysics
研究领域[WOS]: Biochemistry & Molecular Biology ; Biophysics
关键词[WOS]: NITRIC-OXIDE SYNTHASE ; SUBEROYLANILIDE HYDROXAMIC ACID ; LOVASTATIN INDUCES APOPTOSIS ; THYROID-CANCER CELLS ; HUMAN LEUKEMIA-CELLS ; TRICHOSTATIN-A ; PROTEIN GERANYLGERANYLATION ; ENDOTHELIAL-CELLS ; BCL-2 EXPRESSION ; RHO-GTPASES
英文摘要:

HMG-CoA reductase inhibitors and histone deacetylases (HDACs) inhibitors have been shown to induce apoptosis in a variety of cells, which could potentially be used as an anticancer therapy in addition to the designated applications. In the present study, we explored the possible synergistic pro-apoptotic effects and the underlying mechanisms when the two classes of inhibitors were combined. Exposure of HeLa cells to the combined treatment of mevastatin (an inhibitor of HMG-CoA reductase) and trichostatin A (TSA) (an inhibitor of HDACs) synergistically induced apoptosis. Mevastatin treatment transcriptionally and translationally up-regulated RhoA expression in the cells by negative feedback mechanism. While TSA enhanced mevastatin-induced RhoA up-regulation, more importantly, it also accelerated mevastatin-mediated depletion of membrane-bound (geranylgeranylated) RhoA. Moreover, TSA treatment down-regulated protein geranylgeranyl transferase-I (GGTase-I) beta subunit expression, which is one of the key enzymes for protein geranylgeranylation. Taken together, TSA down-regulated GGTase-I beta expression, hence enhanced the statin-induced depletion of geranylgeranylated RhoA, which could be an important mechanism for the synergistic induction of the apoptosis. (c) 2007 Elsevier Inc. All rights reserved.

语种: 英语
WOS记录号: WOS:000251494000030
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57216
Appears in Collections:北京大学口腔医学院_期刊论文

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作者单位: 1.Peking Univ, Sch & Hosp Stomatol, Ctr TMJ Disorders, Beijing 100081, Peoples R China
2.Peking Univ, Sch & Hosp Stomatol, Mol Biol Lab, Beijing 100081, Peoples R China
3.St Lukes Episcopal Hosp, Texas Heart Inst, Baylor Coll Med, Div Cardiothorac Surg,Michael E DeBakey Dept Surg, Houston, TX 77030 USA

Recommended Citation:
Gan, Yehua,Wang, Jian,Coselli, Joseph,et al. Synergistic induction of apoptosis by HMG-CoA reductase inhibitor and histone deacetylases inhibitor in HeLa cells[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2008,365(2):386-392.
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