An ultrasensitive fluorogenic probe for revealing the role of glutathione in chemotherapy resistance

doi:10.1039/c7sc03338a

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	An ultrasensitive fluorogenic probe for revealing the role of glutathione in chemotherapy resistance
	Jiang, Yuejing 2,4; Cheng, Juan 3; Yang, Chengyu 1; Hu, Yongzhou 3; Li, Jia4 ; Han, Yifeng 1; Zang, Yi4 ; Li, Xin 3
刊名	CHEMICAL SCIENCE
	2017-12-01
卷号	8 期号:12 页码:8012-8018
ISSN号	2041-6520
DOI	10.1039/c7sc03338a
文献子类	Article
英文摘要	Unveiling the detailed roles of glutathione (GSH) in chemoresistance necessitates a reliable assay for its detection in intact live specimens. Herein, by taking advantage of the susceptibility of electron-poor C-sp2-S-sufinyl bond to GSH nucleophilic attack, we developed a naphthalimide-sulfoxide based fluorogenic probe (Na-8) applicable for tracking endogenous GSH fluctuation in live cells. Na-8 features a high degree of sensitivity towards GSH as demonstrated by its utmost 2200-fold fluorogenic response. As a proof of concept, Na-8 has been applied to image GSH in liver cancer HepG2 cells with the normal L02 cell counterparts serving as a control, and elevated GSH level was observed in HepG2 in contrast to L02. Further experiments showed that this elevated GSH level was involved in doxorubicin-resistance but not in cisplatin-resistance. Noteworthy, monitoring GSH change in HepG2 and L02 cells in response to doxorubicin treatment revealed that while normal cells showed a burst of GSH in adaption to doxorubicin treatment, no significant change was detected in HepG2 cells, suggesting that HepG2 cells have been preconditioned by their intrinsic oxidative stress which confers drug-resistance. Given the observed sensitivity and spatiotemporal resolution, Na-8 should hold promise for future study on the detailed roles of GSH in drug-resistance.
资助项目	National Natural Science Foundations of China[21642007] ; National Natural Science Foundations of China[81673489] ; National Natural Science Foundations of China[21778048] ; Zhejiang Provincial Natural Science Foundation of China[LY15H300003] ; Zhejiang Provincial Natural Science Foundation of China[LR18H300001] ; Science and Technology Commission of Shanghai Municipality[16430724100]
WOS关键词	REVERSIBLE FLUORESCENT-PROBES ; DRUG-RESISTANCE ; BUTHIONINE SULFOXIMINE ; CELLULAR GLUTATHIONE ; CANCER ; CELLS ; CISPLATIN ; MELPHALAN ; ACCEPTOR ; PROTEIN
WOS研究方向	Chemistry
语种	英语
出版者	ROYAL SOC CHEMISTRY
WOS记录号	WOS:000415877000016
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272382]
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	Zang, Yi; Li, Xin
作者单位	1.Zhejiang Sci Tech Univ, Dept Chem, Hangzhou 310018, Zhejiang, Peoples R China; 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou 310058, Zhejiang, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Jiang, Yuejing,Cheng, Juan,Yang, Chengyu,et al. An ultrasensitive fluorogenic probe for revealing the role of glutathione in chemotherapy resistance[J]. CHEMICAL SCIENCE,2017,8(12):8012-8018.
APA	Jiang, Yuejing.,Cheng, Juan.,Yang, Chengyu.,Hu, Yongzhou.,Li, Jia.,...&Li, Xin.(2017).An ultrasensitive fluorogenic probe for revealing the role of glutathione in chemotherapy resistance.CHEMICAL SCIENCE,8(12),8012-8018.
MLA	Jiang, Yuejing,et al."An ultrasensitive fluorogenic probe for revealing the role of glutathione in chemotherapy resistance".CHEMICAL SCIENCE 8.12(2017):8012-8018.