Kinase-Based Screening of Marine Natural Extracts Leads to the Identification of a Cytotoxic High Molecular Weight Metabolite from the Mediterranean Sponge Crambe tailliezi
by
Thi-Ngoc-Dung Nguyen 1,2, Omid Feizbakhsh 1, Estelle Sfecci 3, Blandine Baratte 1,4, Claire Delehouzé 1,5, Adrien Garcia 3, Corentin Moulin 3, Pierre Colas 1, Sandrine Ruchaud 1,*, Mohamed Mehiri 3,* and Stéphane Bach 1,4,*
Thi-Ngoc-Dung Nguyen 1,2, Omid Feizbakhsh 1, Estelle Sfecci 3, Blandine Baratte 1,4, Claire Delehouzé 1,5, Adrien Garcia 3, Corentin Moulin 3, Pierre Colas 1, Sandrine Ruchaud 1,*, Mohamed Mehiri 3,* and Stéphane Bach 1,4,*
1
Integrative Biology of Marine Models Laboratory (LBI2M), Sorbonne Université, CNRS, UMR 8227, Station Biologique de Roscoff, CS 90074, 29688 Roscoff Cedex, France
2
Department of Chemical Analysis and Drug Quality Control, Faculty of Pharmacy, University of Medicine and Pharmacy, Ho Chi Minh City 70000, Vietnam
3
Marine Natural Products Team, Université Côte d’Azur, CNRS, Institut de Chimie de Nice, UMR 7272, 06108 Nice, France
4
Sorbonne Université, CNRS, Station Biologique de Roscoff, FR 2424, Plateforme de criblage KISSf (Kinase Inhibitor Specialized Screening facility), Place Georges Teissier, 29682 Roscoff, France
5
SeaBeLife Biotech, Place Georges Teissier, 29682 Roscoff, France
*
Authors to whom correspondence should be addressed.
Mar. Drugs 2019, 17(10), 569; https://doi.org/10.3390/md17100569
Received: 6 September 2019 / Revised: 4 October 2019 / Accepted: 7 October 2019 / Published: 9 October 2019
(This article belongs to the Special Issue High-Throughput Screening of Marine Resources)
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.
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Keywords:
Screening; kinase inhibition; regulated cell death; RIP1-independent cell death; marine natural products; Crambe tailliezi
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MDPI and ACS Style
Nguyen, T.-N.-D.; Feizbakhsh, O.; Sfecci, E.; Baratte, B.; Delehouzé, C.; Garcia, A.; Moulin, C.; Colas, P.; Ruchaud, S.; Mehiri, M.; Bach, S. Kinase-Based Screening of Marine Natural Extracts Leads to the Identification of a Cytotoxic High Molecular Weight Metabolite from the Mediterranean Sponge Crambe tailliezi. Mar. Drugs 2019, 17, 569.
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