Curcusone D, a novel ubiquitin-proteasome pathway inhibitor via ROS-induced DUB inhibition, is synergistic with bortezomib against multiple myeloma cell growth

	Curcusone D, a novel ubiquitin-proteasome pathway inhibitor via ROS-induced DUB inhibition, is synergistic with bortezomib against multiple myeloma cell growth
	Cao, Mei-Na ; Zhou, Yu-Bo ; Gao, An-Hui ; Cao, Jia-Yi ; Gao, Li-Xin ; Sheng, Li ; Xu, Lei ; Su, Ming-Bo ; Cao, Xian-Chao ; Han, Meng-meng ; Wang, Ming-Kui ; Li, Jia
刊名	BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
	2014
卷号	1840 期号:6 页码:2004-2013
关键词	Ubiquitin-proteasome pathway Deubiquitinase ROS Curcusone D Bortezomib Multiple myeloma
通讯作者	Zhou, YB (reprint author), 189 Guo Shou Jing Rd, Shanghai 201203, Peoples R China.
产权排序	2
合作状况	其它
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.
学科主题	Biochemistry & Molecular Biology; Biophysics
收录类别	SCI
语种	英语
公开日期	2016-02-26
内容类型	期刊论文
源URL	[http://210.75.237.14/handle/351003/26682]
专题	成都生物研究所_天然产物研究
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.