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1.
Mar Drugs ; 18(12)2020 Dec 04.
Article in English | MEDLINE | ID: mdl-33291602

ABSTRACT

The marine environment is a rich source of biologically active molecules for the treatment of human diseases, especially cancer. The adaptation to unique environmental conditions led marine organisms to evolve different pathways than their terrestrial counterparts, thus producing unique chemicals with a broad diversity and complexity. So far, more than 36,000 compounds have been isolated from marine micro- and macro-organisms including but not limited to fungi, bacteria, microalgae, macroalgae, sponges, corals, mollusks and tunicates, with hundreds of new marine natural products (MNPs) being discovered every year. Marine-based pharmaceuticals have started to impact modern pharmacology and different anti-cancer drugs derived from marine compounds have been approved for clinical use, such as: cytarabine, vidarabine, nelarabine (prodrug of ara-G), fludarabine phosphate (pro-drug of ara-A), trabectedin, eribulin mesylate, brentuximab vedotin, polatuzumab vedotin, enfortumab vedotin, belantamab mafodotin, plitidepsin, and lurbinectedin. This review focuses on the bioactive molecules derived from the marine environment with anticancer activity, discussing their families, origin, structural features and therapeutic use.


Subject(s)
Antineoplastic Agents/chemistry , Aquatic Organisms/chemistry , Marine Toxins/chemistry , Animals , Biological Products , Drug Discovery , Humans , Neoplasms/drug therapy , Water Microbiology
2.
Mar Drugs ; 17(10)2019 Oct 09.
Article in English | MEDLINE | ID: mdl-31600933

ABSTRACT

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.


Subject(s)
Biological Products/pharmacology , Crambe Sponge/chemistry , Crambe Sponge/metabolism , Cytotoxins/pharmacology , Animals , Apoptosis/drug effects , Cell Line , Cell Line, Tumor , Cell Proliferation/drug effects , HEK293 Cells , Hep G2 Cells , Humans , MCF-7 Cells , Mediterranean Sea , Molecular Weight , Protein Kinase Inhibitors/pharmacology , Protein Kinases/metabolism , Signal Transduction/drug effects
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