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Cell Stress, Canonical and Non-Canonical Cell Death Modalities by Marine Natural Compounds and Derivatives

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A special issue of Marine Drugs (ISSN 1660-3397).

Deadline for manuscript submissions: closed (10 November 2019) | Viewed by 17336

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Special Issue Editor

Prof. Dr. Marc Diederich

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Guest Editor

Department of Pharmacy, College of Pharmacy, Seoul National University, Building 29 Room 223, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea
Interests: oncology; signal transduction; cell death; inflammation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue will focus on the discovery of novel cytostatic and cytotoxic agents of marine origin, with a focus on the cellular mechanisms the lead to cell cycle inhibition, cell stress, and diverse cell death modalities.

By now, programmed cell death modalities that use non-canonical pathways different from the well-established apoptotic mechanisms are beginning to be better understood. Considering that many cancer types can develop resistance mechanisms against apoptotic cell death, pharmacologically active compounds, in particular of marine origins could be new sources and provide ideas for drugs triggering cell death modalities including controlled necrosis, parthanatos, ferroptosis and more.

Interestingly, compounds able to trigger stress leading to ER stress or autophagic stress responses were recently described also to trigger hallmarks of immunogenic cell death when dying cells liberate so-called danger associated molecular patterns. Marine compounds remain largely unexplored for their capacities to activate such cell death modalities, and innovating contributions in this field are highly welcome.

Prof. Dr. Marc Diederich
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Marine Drugs is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Apoptosis
Controlled necrosis
Endoplasmic reticulum stress
Autophagy
Immunogenic cell death
DAMPs

Published Papers (4 papers)

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Research

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18 pages, 7443 KiB

Open AccessArticle

Neurymenolide A, a Novel Mitotic Spindle Poison from the New Caledonian Rhodophyta Phacelocarpus neurymenioides

by Sofia-Eléna Motuhi, Omid Feizbakhsh, Béatrice Foll-Josselin, Blandine Baratte, Claire Delehouzé, Arnaud Cousseau, Xavier Fant, Jeannette Chloë Bulinski, Claude Elisabeth Payri, Sandrine Ruchaud, Mohamed Mehiri and Stéphane Bach

Mar. Drugs 2019, 17(2), 93; https://0-doi-org.brum.beds.ac.uk/10.3390/md17020093 - 01 Feb 2019

Cited by 6 | Viewed by 3914

Abstract

The marine α-pyrone macrolide neurymenolide A was previously isolated from the Fijian red macroalga, Neurymenia fraxinifolia, and characterized as an antibacterial agent against antibiotic-resistant strains that also exhibited moderate cytotoxicity in vitro against cancer cell lines. This compound was also shown to exhibit allelopathic effects on Scleractinian corals. However, to date no mechanism of action has been described in the literature. The present study showed, for the first time, the isolation of neurymenolide A from the New Caledonian Rhodophyta, Phacelocarpus neurymenioides. We confirmed the compound’s moderate cytotoxicity in vitro against several human cell lines, including solid and hematological malignancies. Furthermore, we combined fluorescence microscopy and flow cytometry to demonstrate that treatment of U-2 OS osteosarcoma human cells with neurymenolide A could block cell division in prometaphase by inhibiting the correct formation of the mitotic spindle, which induced a mitotic catastrophe that led to necrosis and apoptosis. Absolute configuration of the stereogenic center C-17 of neurymenolide A was deduced by comparison of the experimental and theoretical circular dichroism spectra. Since the total synthesis of this compound has already been described, our findings open new avenues in cancer treatment for this class of marine molecules, including a new source for the natural product. Full article

(This article belongs to the Special Issue Cell Stress, Canonical and Non-Canonical Cell Death Modalities by Marine Natural Compounds and Derivatives)

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19 pages, 3187 KiB

Open AccessArticle

Synergistic AML Cell Death Induction by Marine Cytotoxin (+)-1(R), 6(S), 1’(R), 6’(S), 11(R), 17(S)-Fistularin-3 and Bcl-2 Inhibitor Venetoclax

by Cristina Florean, Kyung Rok Kim, Michael Schnekenburger, Hyun-Jung Kim, Céline Moriou, Cécile Debitus, Mario Dicato, Ali Al-Mourabit, Byung Woo Han and Marc Diederich

Mar. Drugs 2018, 16(12), 518; https://0-doi-org.brum.beds.ac.uk/10.3390/md16120518 - 19 Dec 2018

Cited by 17 | Viewed by 4430

Abstract

Treatment of acute myeloid leukemia (AML) patients is still hindered by resistance and relapse, resulting in an overall poor survival rate. Recently, combining specific B-cell lymphoma (Bcl)-2 inhibitors with compounds downregulating myeloid cell leukemia (Mcl)-1 has been proposed as a new effective strategy to eradicate resistant AML cells. We show here that 1(R), 6(S), 1’(R), 6’(S), 11(R), 17(S)-fistularin-3, a bromotyrosine compound of the fistularin family, isolated from the marine sponge Suberea clavata, synergizes with Bcl-2 inhibitor ABT-199 to efficiently kill Mcl-1/Bcl-2-positive AML cell lines, associated with Mcl-1 downregulation and endoplasmic reticulum stress induction. The absolute configuration of carbons 11 and 17 of the fistularin-3 stereoisomer was fully resolved in this study for the first time, showing that the fistularin we isolated from the marine sponge Subarea clavata is in fact the (+)-11(R), 17(S)-fistularin-3 stereoisomer keeping the known configuration 1(R), 6(S), 1’(R), and 6’(S) for the verongidoic acid part. Docking studies and in vitro assays confirm the potential of this family of molecules to inhibit DNA methyltransferase 1 activity. Full article

(This article belongs to the Special Issue Cell Stress, Canonical and Non-Canonical Cell Death Modalities by Marine Natural Compounds and Derivatives)

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17 pages, 3791 KiB

Open AccessArticle

Transcriptome Analysis of Phycocyanin-Mediated Inhibitory Functions on Non-Small Cell Lung Cancer A549 Cell Growth

by Shuai Hao, Shuang Li, Jing Wang, Lei Zhao, Yan Yan, Qi Cao, Tingting Wu, Liyun Liu and Chengtao Wang

Mar. Drugs 2018, 16(12), 511; https://0-doi-org.brum.beds.ac.uk/10.3390/md16120511 - 15 Dec 2018

Cited by 25 | Viewed by 4821

Abstract

Phycocyanin (PC), derived from cyanobacteria and Spirulina cells, is a type of natural antineoplastic marine protein. It has been reported that phycocyanin exerts an antitumor function in non-small cell lung cancer (NSCLC) cells, but the underlying mechanism has not been elucidated. In this research, a transcriptome study was performed to investigate the regulatory mechanisms of phycocyanin on human NSCLC A549 cells. The survival rate and proliferation ability of A549 cells were markedly reduced by phycocyanin, along with abnormal morphologic changes. The transcriptome analysis showed that 2970 genes were differentially expressed after phycocyanin treatment in A549 cells, including 1431 down-regulated and 1539 up-regulated genes. Gene ontology and KEGG analysis suggested that some classical pathways, such as Wnt, NF-κB, and PI3K-AKT signaling, were significantly enriched. Strikingly, protein–protein interaction (PPI) analysis showed that ubiquitin-C (UBC) occupied the highest degree (the highest number of interactions) in differential genes, indicating that it might play a key role in the phycocyanin-mediated regulatory process in A549 cells. Moreover, qRT-PCR results showed consistent expression trends of differential genes with transcriptome analysis. Consequently, this study has provided a theoretical basis for regulation of phycocyanin in A549 cells, which lays a foundation for the treatment of NSCLC. Full article

(This article belongs to the Special Issue Cell Stress, Canonical and Non-Canonical Cell Death Modalities by Marine Natural Compounds and Derivatives)

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Review

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27 pages, 4926 KiB

Open AccessReview

Different Macrophage Type Triggering as Target of the Action of Biologically Active Substances from Marine Invertebrates

by Lyudmila S. Dolmatova and Igor Yu. Dolmatov

Mar. Drugs 2020, 18(1), 37; https://0-doi-org.brum.beds.ac.uk/10.3390/md18010037 - 02 Jan 2020

Cited by 9 | Viewed by 3469

Abstract

Macrophages play a fundamental role in the immune system. Depending on the microenvironment stimuli, macrophages can acquire distinct phenotypes characterized with different sets of the markers of their functional activities. Polarization of macrophages towards M1 type (classical activation) is involved in inflammation and the related progression of diseases, while, in contrast, alternatively activated M2 macrophages are associated with the anti-inflammatory mechanisms. Reprogramming macrophages to switch their phenotypes could provide a new therapeutic strategy, and targeting the M1/M2 macrophage balance is a promising current trend in pharmacology. Marine invertebrates are a vast source of the variety of structurally diverse compounds with potent pharmacological activities. For years, a large number of studies concerning the immunomodulatory properties of the marine substances have been run with using some intracellular markers of immune stimulation or suppression irrespective of the possible application of marine compounds in reprogramming of macrophage activation, and only few reports clearly demonstrated the macrophage-polarizing activities of some marine compounds during the last decade. In this review, the data on the immunomodulating effects of the extracts and pure compounds of a variety of chemical structure from species of different classes of marine invertebrates are described with focus on their potential in shifting M1/M2 macrophage balance towards M1 or M2 phenotype. Full article

(This article belongs to the Special Issue Cell Stress, Canonical and Non-Canonical Cell Death Modalities by Marine Natural Compounds and Derivatives)

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