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Marine Drugs
Special Issues
Connection of Marine Natural Products and Cell Apoptosis
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Connection of Marine Natural Products and Cell Apoptosis

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

Deadline for manuscript submissions: closed (30 November 2018) | Viewed by 39500

Special Issue Editor

Dr. Esther A. Guzmán

E-Mail Website
Guest Editor
Marine Biomedical and Biotechnology Research, Harbor Branch Oceanographic Institute, Florida Atlantic University, Fort Pierce, Florida, USA
Interests: Immunology; Cancer; Signal Transduction; Cell Biology; Marine Natural Products

Special Issue Information

Dear Colleagues,

Programmed cell death was suspected to exist for many years, but was not fully described or called apoptosis until 1972, when Kerr, Wylie and Currie gave us the hallmarks to define this process. Since then, our focus was on understanding the signalling that directed this event, and what a carefully orchestrated event it turned out to be; with many signalling molecules that drive the process, many that regulate it and even others that stop it. This careful orchestration, along with the conservation of the pathway through species, highlights the importance of apoptosis to the well-being of a cell (and of an organism) from development to fighting off disease and infections. Apoptosis, though, is not alone. We now understand that in addition to apoptosis there are other forms of regulated cell death such as necroptosis, a regulated form of necrosis. There are related processes such as autophagy that along with apoptosis regulate cell fate. We also understand that apoptosis occurs beyond the intrinsic and extrinsic pathways with caspase independent forms of apoptosis existing. As our understanding of the molecular process of apoptosis continues to grow, small molecules that can act upon the signalling molecules of this pathway have an increased relevance. This Special Issue will focus on marine natural products that act upon apoptosis in all its forms: promoting it, regulating it, and preventing it. Marine natural products that act upon this pathway not only have therapeutic potential, but may help us further our understanding of the complex processes of cell death and how cell fate is determined.

As Guest Editor, I invite you to contribute to this Special Issue addressing the “Connection of Marine Natural Products and Cell Apoptosis”. Both original research reports and reviews will be published online in Marine Drugs.

Dr. Esther A. Guzmán
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
  • intrinsic pathway
  • extrinsic pathway
  • mitochondrial outer membrane permeabilization
  • caspase cleavage
  • DNA fragmentation
  • anoikis
  • necroptosis
  • Bcl-2 (family)
  • X-IAP
  • death receptor
  • apoptosome
  • BH3-only proteins

Published Papers (6 papers)

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Research

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14 pages, 2375 KiB  
Article
Astaxanthin Restrains Nitrative-Oxidative Peroxidation in Mitochondrial-Mimetic Liposomes: A Pre-Apoptosis Model
by Camila M. Mano, Thais Guaratini, Karina H. M. Cardozo, Pio Colepicolo, Etelvino J. H. Bechara and Marcelo P. Barros
Mar. Drugs 2018, 16(4), 126; https://doi.org/10.3390/md16040126 - 12 Apr 2018
Cited by 16 | Viewed by 4099
Abstract
Astaxanthin (ASTA) is a ketocarotenoid found in many marine organisms and that affords many benefits to human health. ASTA is particularly effective against radical-mediated lipid peroxidation, and recent findings hypothesize a “mitochondrial-targeted” action of ASTA in cells. Therefore, we examined the protective effects [...] Read more.
Astaxanthin (ASTA) is a ketocarotenoid found in many marine organisms and that affords many benefits to human health. ASTA is particularly effective against radical-mediated lipid peroxidation, and recent findings hypothesize a “mitochondrial-targeted” action of ASTA in cells. Therefore, we examined the protective effects of ASTA against lipid peroxidation in zwitterionic phosphatidylcholine liposomes (PCLs) and anionic phosphatidylcholine: phosphatidylglycerol liposomes (PCPGLs), at different pHs (6.2 to 8.0), which were challenged by oxidizing/nitrating conditions that mimic the regular and preapoptotic redox environment of active mitochondria. Pre-apoptotic conditions were created by oxidized/nitr(osyl)ated cytochrome c and resulted in the highest levels of lipoperoxidation in both PCL and PCPGLs (pH 7.4). ASTA was less protective at acidic conditions, especially in anionic PCPGLs. Our data demonstrated the ability of ASTA to hamper oxidative and nitrative events that lead to cytochrome c-peroxidase apoptosis and lipid peroxidation, although its efficiency changes with pH and lipid composition of membranes. Full article
(This article belongs to the Special Issue Connection of Marine Natural Products and Cell Apoptosis)
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18 pages, 10029 KiB  
Article
Marine Bacterial Polysaccharide EPS11 Inhibits Cancer Cell Growth via Blocking Cell Adhesion and Stimulating Anoikis
by Ruobing Cao, Weihua Jin, Yeqi Shan, Ju Wang, Ge Liu, Shan Kuang and Chaomin Sun
Mar. Drugs 2018, 16(3), 85; https://doi.org/10.3390/md16030085 - 08 Mar 2018
Cited by 20 | Viewed by 5081
Abstract
Tumor cells that acquire metastatic potential have developed resistance to anoikis, a cell death process, after detachment from their primary site to the second organ. In this study, we investigated the molecular mechanisms of a novel marine bacterial polysaccharide EPS11 which exerts its [...] Read more.
Tumor cells that acquire metastatic potential have developed resistance to anoikis, a cell death process, after detachment from their primary site to the second organ. In this study, we investigated the molecular mechanisms of a novel marine bacterial polysaccharide EPS11 which exerts its cytotoxic effects through affecting cancer cell adhesion and anoikis. Firstly, we found that EPS11 could significantly affect cell proliferation and block cell adhesion in A549 cells. We further demonstrated that the expression of several cell adhesion associated proteins is downregulated and the filiform structures of cancer cells are destroyed after EPS11 treatment. Interestingly, the destruction of filiform structures in A549 cells by EPS11 is in a dose-dependent manner, and the inhibitory tendency is very consistent with that observed in the cell adhesion assay, which confirms that filiform structures play important roles in modulating cell adhesion. Moreover, we showed that EPS11 induces apoptosis of A549 cells through stimulating βIII-tubulin associated anoikis: (i) EPS11 inhibits the expression of βIII-tubulin in both transcription and translation levels; and (ii) EPS11 treatment dramatically decreases the phosphorylation of protein kinase B (PKB or AKT), a critical downstream effector of βIII-tubulin. Importantly, EPS11 evidently inhibits the growth of A549-derived tumor xenografts in vivo. Thus, our results suggest that EPS11 may be a potential candidate for human non-small cell lung carcinoma treatment via blocking filiform structure mediated adhesion and stimulating βIII-tubulin associated anoikis. Full article
(This article belongs to the Special Issue Connection of Marine Natural Products and Cell Apoptosis)
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19 pages, 5355 KiB  
Article
MSP-4, an Antimicrobial Peptide, Induces Apoptosis via Activation of Extrinsic Fas/FasL- and Intrinsic Mitochondria-Mediated Pathways in One Osteosarcoma Cell Line
by Hsiao-Mei Kuo, Chung-Chih Tseng, Nan-Fu Chen, Ming-Hong Tai, Han-Chun Hung, Chien-Wei Feng, Shu-Yu Cheng, Shi-Ying Huang, Yen-Hsuan Jean and Zhi-Hong Wen
Mar. Drugs 2018, 16(1), 8; https://doi.org/10.3390/md16010008 - 02 Jan 2018
Cited by 36 | Viewed by 8201
Abstract
Osteosarcoma (OS) is a common malignant bone cancer. The relatively high density of a person’s bone structure means low permeability for drugs, and so finding drugs that can be more effective is important and should not be delayed. MSPs are marine antimicrobial peptides [...] Read more.
Osteosarcoma (OS) is a common malignant bone cancer. The relatively high density of a person’s bone structure means low permeability for drugs, and so finding drugs that can be more effective is important and should not be delayed. MSPs are marine antimicrobial peptides (AMP) and natural compounds extracted from Nile tilapia (Oreochromis niloticus). MSP-4 is a part of the AMPs series, with the advantage of having a molecular weight of about 2.7-kDa and anticancer effects, although the responsible anticancer mechanism is not very clear. The goal of this study is to determine the workings of the mechanism associated with apoptosis resulting from MSP-4 in osteosarcoma MG63 cells. The study showed that MSP-4 significantly induced apoptosis in MG63 cells, with Western blot indicating that MSP-4 induced this apoptosis through an intrinsic pathway and an extrinsic pathway. Thus, a pretreatment system with a particular inhibitor of Z-IETD-FMK (caspase-8 inhibitor) and Z-LEHD-FMK (caspase-9 inhibitor) significantly attenuated the cleavage of caspase-3 and prevented apoptosis. These observations indicate that low concentrations of MSP-4 can help induce the apoptosis of MG63 through a Fas/FasL- and mitochondria-mediated pathway and suggest a potentially innovative alternative to the treatment of human osteosarcoma. Full article
(This article belongs to the Special Issue Connection of Marine Natural Products and Cell Apoptosis)
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Review

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14 pages, 1765 KiB  
Review
Regulated Cell Death Signaling Pathways and Marine Natural Products That Target Them
by Esther A. Guzmán
Mar. Drugs 2019, 17(2), 76; https://doi.org/10.3390/md17020076 - 23 Jan 2019
Cited by 20 | Viewed by 4926
Abstract
Our understanding of cell death used to consist in necrosis, an unregulated form, and apoptosis, regulated cell death. That understanding expanded to acknowledge that apoptosis happens through the intrinsic or extrinsic pathways. Actually, many other regulated cell death processes exist, including necroptosis, a [...] Read more.
Our understanding of cell death used to consist in necrosis, an unregulated form, and apoptosis, regulated cell death. That understanding expanded to acknowledge that apoptosis happens through the intrinsic or extrinsic pathways. Actually, many other regulated cell death processes exist, including necroptosis, a regulated form of necrosis, and autophagy-dependent cell death. We also understand that apoptosis occurs beyond the intrinsic and extrinsic pathways with caspase independent forms of apoptosis existing. Our knowledge of the signaling continues to grow, and with that, so does our ability to target different parts of the pathways with small molecules. Marine natural products co-evolve with their targets, and these unique molecules have complex structures with exquisite biological activities and specificities. This article offers a review of our current understanding of the signaling pathways regulating cell death, and highlights marine natural products that can affect these signaling pathways. Full article
(This article belongs to the Special Issue Connection of Marine Natural Products and Cell Apoptosis)
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31 pages, 2572 KiB  
Review
New Drugs from the Sea: Pro-Apoptotic Activity of Sponges and Algae Derived Compounds
by Giuseppe Ercolano, Paola De Cicco and Angela Ianaro
Mar. Drugs 2019, 17(1), 31; https://doi.org/10.3390/md17010031 - 07 Jan 2019
Cited by 61 | Viewed by 9697
Abstract
Natural compounds derived from marine organisms exhibit a wide variety of biological activities. Over the last decades, a great interest has been focused on the anti-tumour role of sponges and algae that constitute the major source of these bioactive metabolites. A substantial number [...] Read more.
Natural compounds derived from marine organisms exhibit a wide variety of biological activities. Over the last decades, a great interest has been focused on the anti-tumour role of sponges and algae that constitute the major source of these bioactive metabolites. A substantial number of chemically different structures from different species have demonstrated inhibition of tumour growth and progression by inducing apoptosis in several types of human cancer. The molecular mechanisms by which marine natural products activate apoptosis mainly include (1) a dysregulation of the mitochondrial pathway; (2) the activation of caspases; and/or (3) increase of death signals through transmembrane death receptors. This great variety of mechanisms of action may help to overcome the multitude of resistances exhibited by different tumour specimens. Therefore, products from marine organisms and their synthetic derivates might represent promising sources for new anticancer drugs, both as single agents or as co-adjuvants with other chemotherapeutics. This review will focus on some selected bioactive molecules from sponges and algae with pro-apoptotic potential in tumour cells. Full article
(This article belongs to the Special Issue Connection of Marine Natural Products and Cell Apoptosis)
15 pages, 10289 KiB  
Review
Recent Synthesis and Discovery of Brefeldin A Analogs
by Seung-Mann Paek
Mar. Drugs 2018, 16(4), 133; https://doi.org/10.3390/md16040133 - 18 Apr 2018
Cited by 21 | Viewed by 6862
Abstract
The recent development of analogs of brefeldin A (BFA), a fungal metabolite, for the improvement of BFA apoptosis-inducing activity is described. BFA has been isolated from various soil or, more recently, marine fungi and has shown versatile beneficial activities. More importantly, the apoptosis-inducing [...] Read more.
The recent development of analogs of brefeldin A (BFA), a fungal metabolite, for the improvement of BFA apoptosis-inducing activity is described. BFA has been isolated from various soil or, more recently, marine fungi and has shown versatile beneficial activities. More importantly, the apoptosis-inducing activity of BFA in cancer cells highlights the possibility of further developing this natural product as an anticancer agent. Besides its biological importance, its structural features have also gathered tremendous interest from both medicinal and synthetic chemists. By a medicinal chemistry and total synthesis approach, numerous analogs from BFA have been developed to improve its inferior bioavailability and its antiproliferative ability. In this review, the recent medicinal chemistry efforts in relation to the production of BFA analogs are extensively presented. Full article
(This article belongs to the Special Issue Connection of Marine Natural Products and Cell Apoptosis)
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