Targeting phosphoglycerate kinases by tatridin A, a natural sesquiterpenoid endowed with anti-cancer activity, using a proteomic platform
Tatridin A (TatA) is a germacrane sesquiterpenoid containing one E-double bond and one Z-double bond in its 10-membered ring, which is fused to a 3-methylene-dihydrofuran-2-one moiety. Tatridin A bioactivity has been poorly investigated despite its interesting chemical structure. Here, a functional...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1212541/full |
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| author | Giusy Ferraro Giusy Ferraro Antonia Voli Antonia Voli Matteo Mozzicafreddo Federica Pollastro Federica Pollastro Alessandra Tosco Maria Chiara Monti |
| author_facet | Giusy Ferraro Giusy Ferraro Antonia Voli Antonia Voli Matteo Mozzicafreddo Federica Pollastro Federica Pollastro Alessandra Tosco Maria Chiara Monti |
| author_sort | Giusy Ferraro |
| collection | DOAJ |
| description | Tatridin A (TatA) is a germacrane sesquiterpenoid containing one E-double bond and one Z-double bond in its 10-membered ring, which is fused to a 3-methylene-dihydrofuran-2-one moiety. Tatridin A bioactivity has been poorly investigated despite its interesting chemical structure. Here, a functional proteomic platform was adapted to disclose its most reliable targets in leukemia monocytic cells, and phosphoglycerate kinases were recognized as the most affine enzymes. Through a combination of limited proteolysis and molecular docking, it has been discovered that tatridin A interacts with the active domains of phosphoglycerate kinase 1, altering its hinge region, and it can be accountable for tatridin A inhibition potency on enzyme activity. A more detailed tatridin A biological profile showed that it is also fully active against gastric cancer cells, downregulating the mRNA levels of chemokine receptor 4 and β-catenin and inhibiting the invasiveness of living KATO III cells as a direct consequence of phosphoglycerate kinase 1 antagonism. |
| first_indexed | 2024-03-12T01:33:56Z |
| format | Article |
| id | doaj.art-21c56b6aee824cc683d27bfaaeb6c1b6 |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-03-12T01:33:56Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-21c56b6aee824cc683d27bfaaeb6c1b62023-09-11T11:35:43ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2023-09-011010.3389/fmolb.2023.12125411212541Targeting phosphoglycerate kinases by tatridin A, a natural sesquiterpenoid endowed with anti-cancer activity, using a proteomic platformGiusy Ferraro0Giusy Ferraro1Antonia Voli2Antonia Voli3Matteo Mozzicafreddo4Federica Pollastro5Federica Pollastro6Alessandra Tosco7Maria Chiara Monti8Department of Pharmacy, Università di Salerno, Fisciano, ItalyPhD Program in Drug Discovery and Development, Department of Pharmacy, Università di Salerno, Fisciano, ItalyDepartment of Pharmacy, Università di Salerno, Fisciano, ItalyPhD Program in Drug Discovery and Development, Department of Pharmacy, Università di Salerno, Fisciano, ItalyDepartment of Clinical and Molecular Sciences, Università Politecnica Delle Marche, Ancona, ItalyDepartment of Pharmaceutical Sciences, Università Del Piemonte Orientale, Novara, ItalyPlantaChem Srls, Novara, ItalyDepartment of Pharmacy, Università di Salerno, Fisciano, ItalyDepartment of Pharmacy, Università di Salerno, Fisciano, ItalyTatridin A (TatA) is a germacrane sesquiterpenoid containing one E-double bond and one Z-double bond in its 10-membered ring, which is fused to a 3-methylene-dihydrofuran-2-one moiety. Tatridin A bioactivity has been poorly investigated despite its interesting chemical structure. Here, a functional proteomic platform was adapted to disclose its most reliable targets in leukemia monocytic cells, and phosphoglycerate kinases were recognized as the most affine enzymes. Through a combination of limited proteolysis and molecular docking, it has been discovered that tatridin A interacts with the active domains of phosphoglycerate kinase 1, altering its hinge region, and it can be accountable for tatridin A inhibition potency on enzyme activity. A more detailed tatridin A biological profile showed that it is also fully active against gastric cancer cells, downregulating the mRNA levels of chemokine receptor 4 and β-catenin and inhibiting the invasiveness of living KATO III cells as a direct consequence of phosphoglycerate kinase 1 antagonism.https://www.frontiersin.org/articles/10.3389/fmolb.2023.1212541/fullsesquiterpenesfunctional proteomicsPGK1CXCR4gastric cancercancer dissemination |
| spellingShingle | Giusy Ferraro Giusy Ferraro Antonia Voli Antonia Voli Matteo Mozzicafreddo Federica Pollastro Federica Pollastro Alessandra Tosco Maria Chiara Monti Targeting phosphoglycerate kinases by tatridin A, a natural sesquiterpenoid endowed with anti-cancer activity, using a proteomic platform Frontiers in Molecular Biosciences sesquiterpenes functional proteomics PGK1 CXCR4 gastric cancer cancer dissemination |
| title | Targeting phosphoglycerate kinases by tatridin A, a natural sesquiterpenoid endowed with anti-cancer activity, using a proteomic platform |
| title_full | Targeting phosphoglycerate kinases by tatridin A, a natural sesquiterpenoid endowed with anti-cancer activity, using a proteomic platform |
| title_fullStr | Targeting phosphoglycerate kinases by tatridin A, a natural sesquiterpenoid endowed with anti-cancer activity, using a proteomic platform |
| title_full_unstemmed | Targeting phosphoglycerate kinases by tatridin A, a natural sesquiterpenoid endowed with anti-cancer activity, using a proteomic platform |
| title_short | Targeting phosphoglycerate kinases by tatridin A, a natural sesquiterpenoid endowed with anti-cancer activity, using a proteomic platform |
| title_sort | targeting phosphoglycerate kinases by tatridin a a natural sesquiterpenoid endowed with anti cancer activity using a proteomic platform |
| topic | sesquiterpenes functional proteomics PGK1 CXCR4 gastric cancer cancer dissemination |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1212541/full |
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