Drug affinity-responsive target stability unveils filamins as biological targets for artemetin, an anti-cancer flavonoid
Artemetin is a valuable 5-hydroxy-3,6,7,3′,4′-pentamethoxyflavone present in many different medicinal plants with very good oral bioavailability and drug-likeness values, owing to numerous bioactivities, such as anti-inflammatory and anti-cancer ones. Here, a multi-disciplinary plan has been settled...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2022.964295/full |
| _version_ | 1817998547084115968 |
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| author | Giusy Ferraro Giusy Ferraro Raffaella Belvedere Antonello Petrella Alessandra Tosco Björn Stork Stefano Salamone Stefano Salamone Alberto Minassi Alberto Minassi Federica Pollastro Federica Pollastro Elva Morretta Maria Chiara Monti |
| author_facet | Giusy Ferraro Giusy Ferraro Raffaella Belvedere Antonello Petrella Alessandra Tosco Björn Stork Stefano Salamone Stefano Salamone Alberto Minassi Alberto Minassi Federica Pollastro Federica Pollastro Elva Morretta Maria Chiara Monti |
| author_sort | Giusy Ferraro |
| collection | DOAJ |
| description | Artemetin is a valuable 5-hydroxy-3,6,7,3′,4′-pentamethoxyflavone present in many different medicinal plants with very good oral bioavailability and drug-likeness values, owing to numerous bioactivities, such as anti-inflammatory and anti-cancer ones. Here, a multi-disciplinary plan has been settled and applied for identifying the artemetin target(s) to inspect its mechanism of action, based on drug affinity-responsive target stability and targeted limited proteolysis. Both approaches point to the disclosure of filamins A and B as direct artemetin targets in HeLa cell lysates, also giving detailed insights into the ligand/protein-binding sites. Interestingly, also 8-prenyl-artemetin, which is an artemetin more permeable semisynthetic analog, directly interacts with filamins A and B. Both compounds alter filamin conformation in living HeLa cells with an effect on cytoskeleton disassembly and on the disorganization of the F-actin filaments. Both the natural compound and its derivative are able to block cell migration, expectantly acting on tumor metastasis occurrence and development. |
| first_indexed | 2024-04-14T02:54:48Z |
| format | Article |
| id | doaj.art-75995245eb844cd7905f4c47e674e31f |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-04-14T02:54:48Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-75995245eb844cd7905f4c47e674e31f2022-12-22T02:16:08ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2022-08-01910.3389/fmolb.2022.964295964295Drug affinity-responsive target stability unveils filamins as biological targets for artemetin, an anti-cancer flavonoidGiusy Ferraro0Giusy Ferraro1Raffaella Belvedere2Antonello Petrella3Alessandra Tosco4Björn Stork5Stefano Salamone6Stefano Salamone7Alberto Minassi8Alberto Minassi9Federica Pollastro10Federica Pollastro11Elva Morretta12Maria Chiara Monti13Department 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, ItalyDepartment of Pharmacy, Università di Salerno, Fisciano, ItalyDepartment of Pharmacy, Università di Salerno, Fisciano, ItalyInstitute of Molecular Medicine I, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, GermanyDipartimento di Scienze del Farmaco, Università del Piemonte Orientale, Novara, ItalyPlantaChem Srls, Novara, ItalyDipartimento di Scienze del Farmaco, Università del Piemonte Orientale, Novara, ItalyPlantaChem Srls, Novara, ItalyDipartimento di Scienze del Farmaco, Università del Piemonte Orientale, Novara, ItalyPlantaChem Srls, Novara, ItalyDepartment of Pharmacy, Università di Salerno, Fisciano, ItalyDepartment of Pharmacy, Università di Salerno, Fisciano, ItalyArtemetin is a valuable 5-hydroxy-3,6,7,3′,4′-pentamethoxyflavone present in many different medicinal plants with very good oral bioavailability and drug-likeness values, owing to numerous bioactivities, such as anti-inflammatory and anti-cancer ones. Here, a multi-disciplinary plan has been settled and applied for identifying the artemetin target(s) to inspect its mechanism of action, based on drug affinity-responsive target stability and targeted limited proteolysis. Both approaches point to the disclosure of filamins A and B as direct artemetin targets in HeLa cell lysates, also giving detailed insights into the ligand/protein-binding sites. Interestingly, also 8-prenyl-artemetin, which is an artemetin more permeable semisynthetic analog, directly interacts with filamins A and B. Both compounds alter filamin conformation in living HeLa cells with an effect on cytoskeleton disassembly and on the disorganization of the F-actin filaments. Both the natural compound and its derivative are able to block cell migration, expectantly acting on tumor metastasis occurrence and development.https://www.frontiersin.org/articles/10.3389/fmolb.2022.964295/fulldrug affinity-responsive target stabilityproteomicscytoskeletonanti-cancerbioactive natural compounds |
| spellingShingle | Giusy Ferraro Giusy Ferraro Raffaella Belvedere Antonello Petrella Alessandra Tosco Björn Stork Stefano Salamone Stefano Salamone Alberto Minassi Alberto Minassi Federica Pollastro Federica Pollastro Elva Morretta Maria Chiara Monti Drug affinity-responsive target stability unveils filamins as biological targets for artemetin, an anti-cancer flavonoid Frontiers in Molecular Biosciences drug affinity-responsive target stability proteomics cytoskeleton anti-cancer bioactive natural compounds |
| title | Drug affinity-responsive target stability unveils filamins as biological targets for artemetin, an anti-cancer flavonoid |
| title_full | Drug affinity-responsive target stability unveils filamins as biological targets for artemetin, an anti-cancer flavonoid |
| title_fullStr | Drug affinity-responsive target stability unveils filamins as biological targets for artemetin, an anti-cancer flavonoid |
| title_full_unstemmed | Drug affinity-responsive target stability unveils filamins as biological targets for artemetin, an anti-cancer flavonoid |
| title_short | Drug affinity-responsive target stability unveils filamins as biological targets for artemetin, an anti-cancer flavonoid |
| title_sort | drug affinity responsive target stability unveils filamins as biological targets for artemetin an anti cancer flavonoid |
| topic | drug affinity-responsive target stability proteomics cytoskeleton anti-cancer bioactive natural compounds |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2022.964295/full |
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