Discovery of pseudolaric acid A as a new Hsp90 inhibitor uncovers its potential anticancer mechanism
文献类型：期刊论文
| 作者 | Liu,Jiangxin; Wu,Xing-De; Li,Wenyan; Yuan,Zaifeng; Yang,Kun ; Zhao,Qin-Shi
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| 刊名 | BIOORGANIC CHEMISTRY
 |
| 出版日期 | 2021 |
| 卷号 | 112页码:104963 |
| 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 |
| ISSN号 | 0045-2068 |
| DOI | 10.1016/j.bioorg.2021.104963 |
| 英文摘要 | 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. |
| WOS记录号 | WOS:000661875300003 |
| 源URL | [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. |
入库方式： OAI收割
来源：昆明植物研究所
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