Curcusone D, a novel ubiquitin-proteasome pathway inhibitor via ROS-induced DUB inhibition, is synergistic with bortezomib against multiple myeloma cell growth
文献类型：期刊论文
| 作者 | Cao, Mei-Na1; Zhou, Yu-Bo1 ; Gao, An-Hui1; Cao, Jia-Yi1; Gao, Li-Xin1; Sheng, Li1; Xu, Lei1; Su, Ming-Bo1; Cao, Xian-Chao1; Han, Meng-meng1
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| 刊名 | BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
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| 出版日期 | 2014-06 |
| 卷号 | 1840期号:6页码:2004-2013 |
| 关键词 | Ubiquitin-proteasome pathway Deubiquitinase ROS Curcusone D Bortezomib Multiple myeloma |
| ISSN号 | 0304-4165 |
| DOI | 10.1016/j.bbagen.2014.02.006 |
| 文献子类 | Article |
| 英文摘要 | Background: Ubiquitin-proteasome pathway (UPP) plays a very important role in the degradation of proteins. Finding novel UPP inhibitors is a promising strategy for treating multiple myeloma (MM). Methods: Ub-YFP reporter assays were used as cellular UPP models. MM cell growth, apoptosis and overall death were evaluated with the MTS assay, Annexin V/PI dual-staining flow cytometry, poly (ADP-ribose) polymerase (PARP) cleavage, and PI uptake, respectively. The mechanism of UPP inhibition was analyzed by western blotting for ubiquitin, in vitro and cellular proteasomal and deubiquitinases (DUBS) activity assays. Cellular reactive oxygen species (ROS) were measured with H(2)DCFDA. Results: Curcusone D, identified as a novel UPP inhibitor, causes cell growth inhibition and apoptosis in MM cells. Curcusone D induced the accumulation of poly-ubiquitin-conjugated proteins but could not inhibit proteasomal activity in vitro or in cells. Interestingly, the mono-ubiquitin level and the total cellular DUB activity were significantly downregulated following curcusone D treatment. Furthermore, curcusone D could induce ROS, which were closely correlated with DUB inhibition that could be nearly completely reversed by NAC Finally, curcusone D and the proteasomal inhibitor bortezomib showed a strong synergistic effect against MM cells. Conclusions: Curcusone D is novel UPP inhibitor that acts via the ROS-induced inhibition of DUBs to produce strong growth inhibition and apoptosis of MM cells and synergize with bortezomib. General significance: The anti-MM molecular mechanism study of curcusone D will promote combination therapies with different UPP inhibitors against MM and further support the concept of oxidative stress regulating the activity of DUBs. (C) 2014 Elsevier B.V. All rights reserved. |
| WOS关键词 | INDUCED APOPTOSIS ; DEUBIQUITINATING ENZYMES ; ISOPEPTIDASE ACTIVITY ; OXIDATIVE STRESS ; LEUKEMIA-CELLS ; SYSTEM ; CANCER ; PROSTAGLANDINS ; DESTRUCTION ; ACTIVATION |
| 资助项目 | National Natural Science Foundation of China[91029716] ; National Natural Science Foundation of China[81072667] ; National Natural Science Foundation of China[81125023] ; National Science and Technology Major Projects for "Major New Drugs Innovation and Development"[2012ZX09301001-004] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Biophysics |
| 语种 | 英语 |
| WOS记录号 | WOS:000336012700041 |
| 出版者 | ELSEVIER SCIENCE BV |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277057]  |
| 专题 | 国家新药筛选中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Zhou, Yu-Bo |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Chengdu Inst Biol, Chengdu 610041, Peoples R China |
| 推荐引用方式 GB/T 7714 | Cao, Mei-Na,Zhou, Yu-Bo,Gao, An-Hui,et al. Curcusone D, a novel ubiquitin-proteasome pathway inhibitor via ROS-induced DUB inhibition, is synergistic with bortezomib against multiple myeloma cell growth[J]. BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS,2014,1840(6):2004-2013. |
| APA | Cao, Mei-Na.,Zhou, Yu-Bo.,Gao, An-Hui.,Cao, Jia-Yi.,Gao, Li-Xin.,...&Li, Jia.(2014).Curcusone D, a novel ubiquitin-proteasome pathway inhibitor via ROS-induced DUB inhibition, is synergistic with bortezomib against multiple myeloma cell growth.BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS,1840(6),2004-2013. |
| MLA | Cao, Mei-Na,et al."Curcusone D, a novel ubiquitin-proteasome pathway inhibitor via ROS-induced DUB inhibition, is synergistic with bortezomib against multiple myeloma cell growth".BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS 1840.6(2014):2004-2013. |
入库方式： OAI收割
来源：上海药物研究所
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