A quantitative chemical proteomics approach to profile the specific cellular targets of andrographolide, a promising anticancer agent that suppresses tumor metastasis
Drug target identification is a critical step toward understanding the mechanism of action of a drug, which can help one improve the drug's current therapeutic regime and expand the drug's therapeutic potential. However, current in vitro affinity-chromatography-based and in vivo activity-based protein profiling approaches generally face difficulties in discriminating specific drug targets from nonspecific ones. Here we describe a novel approach combining isobaric tags for relative and absolute quantitation with clickable activity-based protein profiling to specifically and comprehensively identify the protein targets of andrographolide (Andro), a natural product with known anti-inflammation and anti-cancer effects, in live cancer cells. We identified a spectrum of specific targets of Andro, which furthered our understanding of the mechanism of action of the drug. Our findings, validated through cell migration and invasion assays, showed that Andro has a potential novel application as a tumor metastasis inhibitor. Moreover, we have unveiled the target binding mechanism of Andro with a combination of drug analog synthesis, protein engineering, and mass-spectrometry-based approaches and determined the drug-binding sites of two protein targets, NF-κB and actin.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2014 |
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| Erschienen: |
2014 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Molecular & cellular proteomics : MCP - 13(2014), 3 vom: 04. März, Seite 876-86 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Jigang [VerfasserIn] |
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| Links: |
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| Themen: |
410105JHGR |
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| Anmerkungen: |
Date Completed 24.10.2014 Date Revised 31.03.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1074/mcp.M113.029793 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM234675284 |
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| 245 | 1 | 2 | |a A quantitative chemical proteomics approach to profile the specific cellular targets of andrographolide, a promising anticancer agent that suppresses tumor metastasis |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Drug target identification is a critical step toward understanding the mechanism of action of a drug, which can help one improve the drug's current therapeutic regime and expand the drug's therapeutic potential. However, current in vitro affinity-chromatography-based and in vivo activity-based protein profiling approaches generally face difficulties in discriminating specific drug targets from nonspecific ones. Here we describe a novel approach combining isobaric tags for relative and absolute quantitation with clickable activity-based protein profiling to specifically and comprehensively identify the protein targets of andrographolide (Andro), a natural product with known anti-inflammation and anti-cancer effects, in live cancer cells. We identified a spectrum of specific targets of Andro, which furthered our understanding of the mechanism of action of the drug. Our findings, validated through cell migration and invasion assays, showed that Andro has a potential novel application as a tumor metastasis inhibitor. Moreover, we have unveiled the target binding mechanism of Andro with a combination of drug analog synthesis, protein engineering, and mass-spectrometry-based approaches and determined the drug-binding sites of two protein targets, NF-κB and actin | ||
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| 700 | 1 | |a Tan, Xing Fei |e verfasserin |4 aut | |
| 700 | 1 | |a Nguyen, Van Sang |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Peng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Mingming |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Zhengjun |e verfasserin |4 aut | |
| 700 | 1 | |a Lim, Teck Kwang |e verfasserin |4 aut | |
| 700 | 1 | |a He, Yingke |e verfasserin |4 aut | |
| 700 | 1 | |a Ong, Chye Sun |e verfasserin |4 aut | |
| 700 | 1 | |a Lay, Yifei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jianbin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Guili |e verfasserin |4 aut | |
| 700 | 1 | |a Lai, Siew-Li |e verfasserin |4 aut | |
| 700 | 1 | |a Ghosh, Dipanjana |e verfasserin |4 aut | |
| 700 | 1 | |a Mok, Yu Keung |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Han-Ming |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Qingsong |e verfasserin |4 aut | |
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