Discovery of pseudolaric acid A as a new Hsp90 inhibitor uncovers its potential anticancer mechanism

doi:10.1016/j.bioorg.2021.104963

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	Discovery of pseudolaric acid A as a new Hsp90 inhibitor uncovers its potential anticancer mechanism
	Liu,Jiangxin ; Wu,Xing-De ; Li,Wenyan ; Yuan,Zaifeng ; Yang,Kun; Zhao,Qin-Shi
	2021
发表期刊	BIOORGANIC CHEMISTRY
ISSN	0045-2068
卷号	112 页码:104963
摘要	Pseudolaric acid A (PAA), one of the main bioactive ingredients in traditional medicine Pseudolarix cortex, exhibits remarkable anticancer activities. Yet its mechanism of action and molecular target have not been investigated and remain unclear. In this work, mechanistic study showed that PAA induced cell cycle arrest at G2/M phase and promoted cell death through caspase-8/caspase-3 pathway, demonstrating potent antiproliferation and anticancer activities. PAA was discovered to be a new Hsp90 inhibitor and multiple biophysical experiments confirmed that PAA directly bind to Hsp90. Active PAA-probe was designed, synthesized and biological evaluated. It was subsequently employed to verify the cellular interaction with Hsp90 in HeLa cells through photoaffinity labeling approach. Furthermore, NMR experiments showed that N-terminal domain of Hsp90 and essential groups in PAA are important for the protein-inhibitor recognition. Structure-activity relationship studies revealed the correlation between its Hsp90 inhibitory activity with anticancer activity. This work proposed a potential mechanism involved with the anticancer activity of PAA and will improve the appreciation of PAA as a potential cancer therapy candidate.
关键词	Pseudolaric acid A Hsp90 inhibitor Apoptosis NMR Structure-activity relationship Photoaffinity-based probe Protein-ligand interaction MOLECULAR CHAPERONE PROTEIN TARGET CANCER KINASE NMR IDENTIFICATION SELECTIVITY BINDING DESIGN
DOI	10.1016/j.bioorg.2021.104963
WOS记录号	WOS:000661875300003
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/73015
专题	中国科学院昆明植物研究所
作者单位	1.[Liu, Jiangxin 2.Wu, Xing-De 3.Li, Wenyan 4.Yuan, Zaifeng 5.Yang, Kun 6.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China
推荐引用方式 GB/T 7714	Liu,Jiangxin,Wu,Xing-De,Li,Wenyan,et al. Discovery of pseudolaric acid A as a new Hsp90 inhibitor uncovers its potential anticancer mechanism[J]. BIOORGANIC CHEMISTRY,2021,112:104963.
APA	Liu,Jiangxin,Wu,Xing-De,Li,Wenyan,Yuan,Zaifeng,Yang,Kun,&Zhao,Qin-Shi.(2021).Discovery of pseudolaric acid A as a new Hsp90 inhibitor uncovers its potential anticancer mechanism.BIOORGANIC CHEMISTRY,112,104963.
MLA	Liu,Jiangxin,et al."Discovery of pseudolaric acid A as a new Hsp90 inhibitor uncovers its potential anticancer mechanism".BIOORGANIC CHEMISTRY 112(2021):104963.

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