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>
Thi-Ngoc-Dung Nguyen,
Omid Feizbakhsh,
Estelle Sfecci,
Blandine Baratte,
Claire Delehouzé,
Adrien Garcia,
Corentin Moulin,
Pierre Colas,
Sandrine Ruchaud,
Mohamed Mehiri,
Stéphane Bach
Affiliations
Thi-Ngoc-Dung Nguyen
Integrative Biology of Marine Models Laboratory (LBI2M), Sorbonne Université, CNRS, UMR 8227, Station Biologique de Roscoff, CS 90074, 29688 Roscoff Cedex, France
Omid Feizbakhsh
Integrative Biology of Marine Models Laboratory (LBI2M), Sorbonne Université, CNRS, UMR 8227, Station Biologique de Roscoff, CS 90074, 29688 Roscoff Cedex, France
Estelle Sfecci
Marine Natural Products Team, Université Côte d’Azur, CNRS, Institut de Chimie de Nice, UMR 7272, 06108 Nice, France
Blandine Baratte
Integrative Biology of Marine Models Laboratory (LBI2M), Sorbonne Université, CNRS, UMR 8227, Station Biologique de Roscoff, CS 90074, 29688 Roscoff Cedex, France
Claire Delehouzé
Integrative Biology of Marine Models Laboratory (LBI2M), Sorbonne Université, CNRS, UMR 8227, Station Biologique de Roscoff, CS 90074, 29688 Roscoff Cedex, France
Adrien Garcia
Marine Natural Products Team, Université Côte d’Azur, CNRS, Institut de Chimie de Nice, UMR 7272, 06108 Nice, France
Corentin Moulin
Marine Natural Products Team, Université Côte d’Azur, CNRS, Institut de Chimie de Nice, UMR 7272, 06108 Nice, France
Pierre Colas
Integrative Biology of Marine Models Laboratory (LBI2M), Sorbonne Université, CNRS, UMR 8227, Station Biologique de Roscoff, CS 90074, 29688 Roscoff Cedex, France
Sandrine Ruchaud
Integrative Biology of Marine Models Laboratory (LBI2M), Sorbonne Université, CNRS, UMR 8227, Station Biologique de Roscoff, CS 90074, 29688 Roscoff Cedex, France
Mohamed Mehiri
Marine Natural Products Team, Université Côte d’Azur, CNRS, Institut de Chimie de Nice, UMR 7272, 06108 Nice, France
Stéphane Bach
Integrative Biology of Marine Models Laboratory (LBI2M), Sorbonne Université, CNRS, UMR 8227, Station Biologique de Roscoff, CS 90074, 29688 Roscoff Cedex, France
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 Crambe tailliezi 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.