Kinase-Based Screening of Marine Natural Extracts Leads to the Identification of a Cytotoxic High Molecular Weight Metabolite from the Mediterranean Sponge <i>Crambe tailliezi</i>

Regulated cell death (RCD) results from the activation of one or more signal transduction modules both in physiological or pathological conditions. It is now established that RCD is involved in numerous human diseases, including cancer. As regulated cell death processes can be modulated by pharmacol...

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Main Authors: Thi-Ngoc-Dung Nguyen, Omid Feizbakhsh, Estelle Sfecci, Blandine Baratte, Claire Delehouzé, Adrien Garcia, Corentin Moulin, Pierre Colas, Sandrine Ruchaud, Mohamed Mehiri, Stéphane Bach
Format: Article
Language:English
Published: MDPI AG 2019-10-01
Series:Marine Drugs
Subjects:
Online Access:https://www.mdpi.com/1660-3397/17/10/569
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author Thi-Ngoc-Dung Nguyen
Omid Feizbakhsh
Estelle Sfecci
Blandine Baratte
Claire Delehouzé
Adrien Garcia
Corentin Moulin
Pierre Colas
Sandrine Ruchaud
Mohamed Mehiri
Stéphane Bach
author_facet Thi-Ngoc-Dung Nguyen
Omid Feizbakhsh
Estelle Sfecci
Blandine Baratte
Claire Delehouzé
Adrien Garcia
Corentin Moulin
Pierre Colas
Sandrine Ruchaud
Mohamed Mehiri
Stéphane Bach
author_sort Thi-Ngoc-Dung Nguyen
collection DOAJ
description Regulated cell death (RCD) results from the activation of one or more signal transduction modules both in physiological or pathological conditions. It is now established that RCD is involved in numerous human diseases, including cancer. As regulated cell death processes can be modulated by pharmacological tools, the research reported here aims to characterize new marine compounds acting as RCD modulators. Protein kinases (PKs) are key signaling actors in various RCDs notably through the control of either mitosis (e.g., the PKs Aurora A and B) or necroptosis (e.g., RIPK1 and RIPK3). From the primary screening of 27 various extracts of marine organisms collected in the Mediterranean Sea, an extract and subsequently a purified high molecular weight compound dubbed P3, were isolated from the marine sponge <i>Crambe tailliezi</i> and characterized as a selective inhibitor of PKs Aurora A and B. Furthermore, P3 was shown to induce apoptosis and to decrease proliferation and mitotic index of human osteosarcoma U-2 OS cells.
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spelling doaj.art-efe9d9089528481dabd378f52d0fc0972022-12-22T04:00:08ZengMDPI AGMarine Drugs1660-33972019-10-01171056910.3390/md17100569md17100569Kinase-Based Screening of Marine Natural Extracts Leads to the Identification of a Cytotoxic High Molecular Weight Metabolite from the Mediterranean Sponge <i>Crambe tailliezi</i>Thi-Ngoc-Dung Nguyen0Omid Feizbakhsh1Estelle Sfecci2Blandine Baratte3Claire Delehouzé4Adrien Garcia5Corentin Moulin6Pierre Colas7Sandrine Ruchaud8Mohamed Mehiri9Stéphane Bach10Integrative Biology of Marine Models Laboratory (LBI2M), Sorbonne Université, CNRS, UMR 8227, Station Biologique de Roscoff, CS 90074, 29688 Roscoff Cedex, FranceIntegrative Biology of Marine Models Laboratory (LBI2M), Sorbonne Université, CNRS, UMR 8227, Station Biologique de Roscoff, CS 90074, 29688 Roscoff Cedex, FranceMarine Natural Products Team, Université Côte d’Azur, CNRS, Institut de Chimie de Nice, UMR 7272, 06108 Nice, FranceIntegrative Biology of Marine Models Laboratory (LBI2M), Sorbonne Université, CNRS, UMR 8227, Station Biologique de Roscoff, CS 90074, 29688 Roscoff Cedex, FranceIntegrative Biology of Marine Models Laboratory (LBI2M), Sorbonne Université, CNRS, UMR 8227, Station Biologique de Roscoff, CS 90074, 29688 Roscoff Cedex, FranceMarine Natural Products Team, Université Côte d’Azur, CNRS, Institut de Chimie de Nice, UMR 7272, 06108 Nice, FranceMarine Natural Products Team, Université Côte d’Azur, CNRS, Institut de Chimie de Nice, UMR 7272, 06108 Nice, FranceIntegrative Biology of Marine Models Laboratory (LBI2M), Sorbonne Université, CNRS, UMR 8227, Station Biologique de Roscoff, CS 90074, 29688 Roscoff Cedex, FranceIntegrative Biology of Marine Models Laboratory (LBI2M), Sorbonne Université, CNRS, UMR 8227, Station Biologique de Roscoff, CS 90074, 29688 Roscoff Cedex, FranceMarine Natural Products Team, Université Côte d’Azur, CNRS, Institut de Chimie de Nice, UMR 7272, 06108 Nice, FranceIntegrative Biology of Marine Models Laboratory (LBI2M), Sorbonne Université, CNRS, UMR 8227, Station Biologique de Roscoff, CS 90074, 29688 Roscoff Cedex, FranceRegulated cell death (RCD) results from the activation of one or more signal transduction modules both in physiological or pathological conditions. It is now established that RCD is involved in numerous human diseases, including cancer. As regulated cell death processes can be modulated by pharmacological tools, the research reported here aims to characterize new marine compounds acting as RCD modulators. Protein kinases (PKs) are key signaling actors in various RCDs notably through the control of either mitosis (e.g., the PKs Aurora A and B) or necroptosis (e.g., RIPK1 and RIPK3). From the primary screening of 27 various extracts of marine organisms collected in the Mediterranean Sea, an extract and subsequently a purified high molecular weight compound dubbed P3, were isolated from the marine sponge <i>Crambe tailliezi</i> and characterized as a selective inhibitor of PKs Aurora A and B. Furthermore, P3 was shown to induce apoptosis and to decrease proliferation and mitotic index of human osteosarcoma U-2 OS cells.https://www.mdpi.com/1660-3397/17/10/569screeningkinase inhibitionregulated cell deathrip1-independent cell deathmarine natural products<i>crambe tailliezi</i>
spellingShingle Thi-Ngoc-Dung Nguyen
Omid Feizbakhsh
Estelle Sfecci
Blandine Baratte
Claire Delehouzé
Adrien Garcia
Corentin Moulin
Pierre Colas
Sandrine Ruchaud
Mohamed Mehiri
Stéphane Bach
Kinase-Based Screening of Marine Natural Extracts Leads to the Identification of a Cytotoxic High Molecular Weight Metabolite from the Mediterranean Sponge <i>Crambe tailliezi</i>
Marine Drugs
screening
kinase inhibition
regulated cell death
rip1-independent cell death
marine natural products
<i>crambe tailliezi</i>
title Kinase-Based Screening of Marine Natural Extracts Leads to the Identification of a Cytotoxic High Molecular Weight Metabolite from the Mediterranean Sponge <i>Crambe tailliezi</i>
title_full Kinase-Based Screening of Marine Natural Extracts Leads to the Identification of a Cytotoxic High Molecular Weight Metabolite from the Mediterranean Sponge <i>Crambe tailliezi</i>
title_fullStr Kinase-Based Screening of Marine Natural Extracts Leads to the Identification of a Cytotoxic High Molecular Weight Metabolite from the Mediterranean Sponge <i>Crambe tailliezi</i>
title_full_unstemmed Kinase-Based Screening of Marine Natural Extracts Leads to the Identification of a Cytotoxic High Molecular Weight Metabolite from the Mediterranean Sponge <i>Crambe tailliezi</i>
title_short Kinase-Based Screening of Marine Natural Extracts Leads to the Identification of a Cytotoxic High Molecular Weight Metabolite from the Mediterranean Sponge <i>Crambe tailliezi</i>
title_sort kinase based screening of marine natural extracts leads to the identification of a cytotoxic high molecular weight metabolite from the mediterranean sponge i crambe tailliezi i
topic screening
kinase inhibition
regulated cell death
rip1-independent cell death
marine natural products
<i>crambe tailliezi</i>
url https://www.mdpi.com/1660-3397/17/10/569
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