A selenosemicarbazone complex with copper efficiently down-regulates the   90-kDa heat shock protein HSP90AA1 and its client proteins in cancer   cells

doi:10.1186/1471-2407-14-629

CORC > 北京大学 > 化学与分子工程学院

	A selenosemicarbazone complex with copper efficiently down-regulates the 90-kDa heat shock protein HSP90AA1 and its client proteins in cancer cells
	Shen, Hongtao ; Zhu, Haichuan ; Song, Mowei ; Tian, Yonglu ; Huang, Yafei ; Zheng, Hui ; Cao, Ruiyuan ; Lin, Jian ; Bi, Zhenggang ; Zhong, Wu
刊名	bmc cancer
	2014
关键词	Selenosemicarbazone Cell death Oxidative stress RNA-seq HSP90AA1 protein PIM1 AKT1 IN-VIVO METAL-COMPLEXES INHIBITOR APOPTOSIS THIOSEMICARBAZONE GROWTH DEGRADATION AUTOPHAGY COMPOUND SNX-2112
DOI	10.1186/1471-2407-14-629
英文摘要	Background: The 90-kDa heat shock protein HSP90AA1 is critical for the stability of several proteins that are important for tumor progression and thus, is a promising target for cancer therapy. Selenosemicarbazone metal complexes have been shown to possess anticancer activity through an unknown molecular mechanism. Methods: The MTT assay, fluorescence-activated cell sorting, and fluorescent microscopy were used to analyze the mechanism of the anti-cancer activity of the selenosemicarbazone metal complexes. Additionally, RNA seq was applied to identify transcriptional gene changes, and in turn, the signaling pathways involved in the process of 2-24a/Cu-induced cell death. Last, the expression of HSP90AA1, HSPA1A, PIM1, and AKT proteins in 2-24a/Cu-treated cells were investigated by western blot analysis. Results: A novel selenosemicarbazone copper complex (2-24a/Cu) efficiently induced G2/M arrest and was cytotoxic in cancer cells. 2-24a/Cu significantly induced oxidative stress in cancer cells. Interestingly, although RNA-seq revealed that the transcription of HSP90AA1 was increased in 2-24a/Cu-treated cells, western blotting showed that the expression of HSP90AA1 protein was significantly decreased in these cells. Furthermore, down-regulation of HSP90AA1 led to the degradation of its client proteins (PIM1 and AKT1), which are also cancer therapy targets. Conclusion: Our results showed that 2-24a/Cu efficiently generates oxidative stress and down-regulates HSP90AA1 and its client proteins (PIM1, AKT1) in U2os and HeLa cells. These results demonstrate the potential application of this novel copper complex in cancer therapy.; http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000341655700001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701 ; Oncology; SCI(E); 6; ARTICLE; drbizhenggang@163.com; zhongwu@bmi.ac.cn; 14
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/209750]
专题	化学与分子工程学院
推荐引用方式 GB/T 7714	Shen, Hongtao,Zhu, Haichuan,Song, Mowei,et al. A selenosemicarbazone complex with copper efficiently down-regulates the 90-kDa heat shock protein HSP90AA1 and its client proteins in cancer cells[J]. bmc cancer,2014.
APA	Shen, Hongtao.,Zhu, Haichuan.,Song, Mowei.,Tian, Yonglu.,Huang, Yafei.,...&Zhong, Wu.(2014).A selenosemicarbazone complex with copper efficiently down-regulates the 90-kDa heat shock protein HSP90AA1 and its client proteins in cancer cells.bmc cancer.
MLA	Shen, Hongtao,et al."A selenosemicarbazone complex with copper efficiently down-regulates the 90-kDa heat shock protein HSP90AA1 and its client proteins in cancer cells".bmc cancer (2014).