Specific Antiproliferative Properties of Proteinaceous Toxin Secretions from the Marine Annelid <i>Eulalia</i> sp. onto Ovarian Cancer Cells
As Yondelis joins the ranks of approved anti-cancer drugs, the benefit from exploring the oceans’ biodiversity becomes clear. From marine toxins, relevant bioproducts can be obtained due to their potential to interfere with specific pathways. We explored the cytotoxicity of toxin-bearing secretions...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-01-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/19/1/31 |
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| author | Ana P. Rodrigo Vera M. Mendes Bruno Manadas Ana R. Grosso António P. Alves de Matos Pedro V. Baptista Pedro M. Costa Alexandra R. Fernandes |
| author_facet | Ana P. Rodrigo Vera M. Mendes Bruno Manadas Ana R. Grosso António P. Alves de Matos Pedro V. Baptista Pedro M. Costa Alexandra R. Fernandes |
| author_sort | Ana P. Rodrigo |
| collection | DOAJ |
| description | As Yondelis joins the ranks of approved anti-cancer drugs, the benefit from exploring the oceans’ biodiversity becomes clear. From marine toxins, relevant bioproducts can be obtained due to their potential to interfere with specific pathways. We explored the cytotoxicity of toxin-bearing secretions of the polychaete <i>Eulalia</i> onto a battery of normal and cancer human cell lines and discovered that the cocktail of proteins is more toxic towards an ovarian cancer cell line (A2780). The secretions’ main proteins were identified by proteomics and transcriptomics: 14-3-3 protein, Hsp70, Rab3, Arylsulfatase B and serine protease, the latter two being known toxins. This mixture of toxins induces cell-cycle arrest at G2/M phase after 3h exposure in A2780 cells and extrinsic programmed cell death. These findings indicate that partial re-activation of the G2/M checkpoint, which is inactivated in many cancer cells, can be partly reversed by the toxic mixture. Protein–protein interaction networks partake in two cytotoxic effects: cell-cycle arrest with a link to RAB3C and RAF1; and lytic activity of arylsulfatases. The discovery of both mechanisms indicates that venomous mixtures may affect proliferating cells in a specific manner, highlighting the cocktails’ potential in the fine-tuning of anti-cancer therapeutics targeting cell cycle and protein homeostasis. |
| first_indexed | 2024-03-09T05:09:27Z |
| format | Article |
| id | doaj.art-d64564fb0d264b99ad3f1a5b0ffc30e7 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-03-09T05:09:27Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-d64564fb0d264b99ad3f1a5b0ffc30e72023-12-03T12:51:31ZengMDPI AGMarine Drugs1660-33972021-01-011913110.3390/md19010031Specific Antiproliferative Properties of Proteinaceous Toxin Secretions from the Marine Annelid <i>Eulalia</i> sp. onto Ovarian Cancer CellsAna P. Rodrigo0Vera M. Mendes1Bruno Manadas2Ana R. Grosso3António P. Alves de Matos4Pedro V. Baptista5Pedro M. Costa6Alexandra R. Fernandes7UCIBIO–Applied Molecular Biosciences Unit, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa, 2829-516 Caparica, PortugalCNC–Center for Neuroscience and Cell Biology, University of Coimbra, 3060-197 Cantanhede, PortugalCNC–Center for Neuroscience and Cell Biology, University of Coimbra, 3060-197 Cantanhede, PortugalUCIBIO–Applied Molecular Biosciences Unit, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa, 2829-516 Caparica, PortugalCentro de Investigação Interdisciplinar Egas Moniz (CiiEM), Quinta da Granja, Monte de Caparica, 2829-516 Caparica, PortugalUCIBIO–Applied Molecular Biosciences Unit, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa, 2829-516 Caparica, PortugalUCIBIO–Applied Molecular Biosciences Unit, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa, 2829-516 Caparica, PortugalUCIBIO–Applied Molecular Biosciences Unit, Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa, 2829-516 Caparica, PortugalAs Yondelis joins the ranks of approved anti-cancer drugs, the benefit from exploring the oceans’ biodiversity becomes clear. From marine toxins, relevant bioproducts can be obtained due to their potential to interfere with specific pathways. We explored the cytotoxicity of toxin-bearing secretions of the polychaete <i>Eulalia</i> onto a battery of normal and cancer human cell lines and discovered that the cocktail of proteins is more toxic towards an ovarian cancer cell line (A2780). The secretions’ main proteins were identified by proteomics and transcriptomics: 14-3-3 protein, Hsp70, Rab3, Arylsulfatase B and serine protease, the latter two being known toxins. This mixture of toxins induces cell-cycle arrest at G2/M phase after 3h exposure in A2780 cells and extrinsic programmed cell death. These findings indicate that partial re-activation of the G2/M checkpoint, which is inactivated in many cancer cells, can be partly reversed by the toxic mixture. Protein–protein interaction networks partake in two cytotoxic effects: cell-cycle arrest with a link to RAB3C and RAF1; and lytic activity of arylsulfatases. The discovery of both mechanisms indicates that venomous mixtures may affect proliferating cells in a specific manner, highlighting the cocktails’ potential in the fine-tuning of anti-cancer therapeutics targeting cell cycle and protein homeostasis.https://www.mdpi.com/1660-3397/19/1/31invertebratecytotoxicitycancerovarian cancerprogrammed cell deathcell cycle |
| spellingShingle | Ana P. Rodrigo Vera M. Mendes Bruno Manadas Ana R. Grosso António P. Alves de Matos Pedro V. Baptista Pedro M. Costa Alexandra R. Fernandes Specific Antiproliferative Properties of Proteinaceous Toxin Secretions from the Marine Annelid <i>Eulalia</i> sp. onto Ovarian Cancer Cells Marine Drugs invertebrate cytotoxicity cancer ovarian cancer programmed cell death cell cycle |
| title | Specific Antiproliferative Properties of Proteinaceous Toxin Secretions from the Marine Annelid <i>Eulalia</i> sp. onto Ovarian Cancer Cells |
| title_full | Specific Antiproliferative Properties of Proteinaceous Toxin Secretions from the Marine Annelid <i>Eulalia</i> sp. onto Ovarian Cancer Cells |
| title_fullStr | Specific Antiproliferative Properties of Proteinaceous Toxin Secretions from the Marine Annelid <i>Eulalia</i> sp. onto Ovarian Cancer Cells |
| title_full_unstemmed | Specific Antiproliferative Properties of Proteinaceous Toxin Secretions from the Marine Annelid <i>Eulalia</i> sp. onto Ovarian Cancer Cells |
| title_short | Specific Antiproliferative Properties of Proteinaceous Toxin Secretions from the Marine Annelid <i>Eulalia</i> sp. onto Ovarian Cancer Cells |
| title_sort | specific antiproliferative properties of proteinaceous toxin secretions from the marine annelid i eulalia i sp onto ovarian cancer cells |
| topic | invertebrate cytotoxicity cancer ovarian cancer programmed cell death cell cycle |
| url | https://www.mdpi.com/1660-3397/19/1/31 |
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