Investigation of targets and anticancer mechanisms of covalently acting natural products by functional proteomics
文献类型：期刊论文
| 作者 | Zhao, Wen-si3,4,5; Chen, Kai-feng3,4,5; Liu, Man5; Jia, Xing-long2,5; Huang, Yu-qi4,5; Hao, Bing-bing5; Hu, Hao5; Shen, Xiao-yan2; Yu, Qiang5 ; Tan, Min-jia1,3,4,5
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| 刊名 | ACTA PHARMACOLOGICA SINICA
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| 出版日期 | 2023-08-01 |
| 卷号 | 44期号:8页码:1701-1711 |
| 关键词 | natural products proteomics ABPP eriocalyxin B parthenolide |
| DOI | 10.1038/s41401-023-01072-z |
| 文献子类 | Article |
| 英文摘要 | Eriocalyxin B (EB), 17-hydroxy-jolkinolide B (HJB), parthenolide (PN), xanthatin (XT) and andrographolide (AG) are terpenoid natural products with a variety of promising antitumor activities, which commonly bear electrophilic groups (alpha,beta-unsaturated carbonyl groups and/or epoxides) capable of covalently modifying protein cysteine residues. However, their direct targets and underlying molecular mechanisms are still largely unclear, which limits the development of these compounds. In this study, we integrated activity-based protein profiling (ABPP) and quantitative proteomics approach to systematically characterize the covalent targets of these natural products and their involved cellular pathways. We first demonstrated the anti-proliferation activities of these five compounds in triple-negative breast cancer cell MDA-MB-231. Tandem mass tag (TMT)-based quantitative proteomics showed all five compounds commonly affected the ubiquitin mediated proteolysis pathways. ABPP platform identified the preferentially modified targets of EB and PN, two natural products with high anti-proliferation activity. Biochemical experiments showed that PN inhibited the cell proliferation through targeting ubiquitin carboxyl-terminal hydrolase 10 (USP10). Together, this study uncovered the covalently modified targets of these natural products and potential molecular mechanisms of their antitumor activities. |
| WOS关键词 | NF-KAPPA-B ; SESQUITERPENE LACTONE ; RATIO COMPRESSION ; MASS-SPECTROMETRY ; BREAST-CANCER ; TUMOR-GROWTH ; PARTHENOLIDE ; SUPPRESSES ; INHIBITION ; DISCOVERY |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| 出版者 | NATURE PUBL GROUP |
| WOS记录号 | WOS:000953152200001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/309668]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Tan, Min-jia |
| 作者单位 | 1.Jiangsu Ocean Univ, Coll Pharm, Jiangsu Key Lab Marine Pharmaceut Cpd Screening, Lianyungang 222005, Peoples R China 2.Fudan Univ, Sch Pharm, Dept Pharmacol, Shanghai 201203, Peoples R China; 3.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Peoples R China; 4.Univ Chinese Acad Sci, Beijing 101408, Peoples R China; 5.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 | Zhao, Wen-si,Chen, Kai-feng,Liu, Man,et al. Investigation of targets and anticancer mechanisms of covalently acting natural products by functional proteomics[J]. ACTA PHARMACOLOGICA SINICA,2023,44(8):1701-1711. |
| APA | Zhao, Wen-si.,Chen, Kai-feng.,Liu, Man.,Jia, Xing-long.,Huang, Yu-qi.,...&Tan, Min-jia.(2023).Investigation of targets and anticancer mechanisms of covalently acting natural products by functional proteomics.ACTA PHARMACOLOGICA SINICA,44(8),1701-1711. |
| MLA | Zhao, Wen-si,et al."Investigation of targets and anticancer mechanisms of covalently acting natural products by functional proteomics".ACTA PHARMACOLOGICA SINICA 44.8(2023):1701-1711. |
入库方式： OAI收割
来源：上海药物研究所
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