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Specific Antiproliferative Properties of Proteinaceous Toxin Secretions from the Marine Annelid Eulalia 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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Autores principales: Rodrigo, Ana P., Mendes, Vera M., Manadas, Bruno, Grosso, Ana R., Alves de Matos, António P., Baptista, Pedro V., Costa, Pedro M., Fernandes, Alexandra R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827603/
https://www.ncbi.nlm.nih.gov/pubmed/33445445
http://dx.doi.org/10.3390/md19010031
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author Rodrigo, Ana P.
Mendes, Vera M.
Manadas, Bruno
Grosso, Ana R.
Alves de Matos, António P.
Baptista, Pedro V.
Costa, Pedro M.
Fernandes, Alexandra R.
author_facet Rodrigo, Ana P.
Mendes, Vera M.
Manadas, Bruno
Grosso, Ana R.
Alves de Matos, António P.
Baptista, Pedro V.
Costa, Pedro M.
Fernandes, Alexandra R.
author_sort Rodrigo, Ana P.
collection PubMed
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 Eulalia 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.
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spelling pubmed-78276032021-01-25 Specific Antiproliferative Properties of Proteinaceous Toxin Secretions from the Marine Annelid Eulalia sp. onto Ovarian Cancer Cells Rodrigo, Ana P. Mendes, Vera M. Manadas, Bruno Grosso, Ana R. Alves de Matos, António P. Baptista, Pedro V. Costa, Pedro M. Fernandes, Alexandra R. Mar Drugs Article 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 Eulalia 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. MDPI 2021-01-12 /pmc/articles/PMC7827603/ /pubmed/33445445 http://dx.doi.org/10.3390/md19010031 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rodrigo, Ana P.
Mendes, Vera M.
Manadas, Bruno
Grosso, Ana R.
Alves de Matos, António P.
Baptista, Pedro V.
Costa, Pedro M.
Fernandes, Alexandra R.
Specific Antiproliferative Properties of Proteinaceous Toxin Secretions from the Marine Annelid Eulalia sp. onto Ovarian Cancer Cells
title Specific Antiproliferative Properties of Proteinaceous Toxin Secretions from the Marine Annelid Eulalia sp. onto Ovarian Cancer Cells
title_full Specific Antiproliferative Properties of Proteinaceous Toxin Secretions from the Marine Annelid Eulalia sp. onto Ovarian Cancer Cells
title_fullStr Specific Antiproliferative Properties of Proteinaceous Toxin Secretions from the Marine Annelid Eulalia sp. onto Ovarian Cancer Cells
title_full_unstemmed Specific Antiproliferative Properties of Proteinaceous Toxin Secretions from the Marine Annelid Eulalia sp. onto Ovarian Cancer Cells
title_short Specific Antiproliferative Properties of Proteinaceous Toxin Secretions from the Marine Annelid Eulalia sp. onto Ovarian Cancer Cells
title_sort specific antiproliferative properties of proteinaceous toxin secretions from the marine annelid eulalia sp. onto ovarian cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827603/
https://www.ncbi.nlm.nih.gov/pubmed/33445445
http://dx.doi.org/10.3390/md19010031
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