Marine Compounds as Modulators of Autophagy and Lysosomal Activity

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

Deadline for manuscript submissions: closed (31 December 2017) | Viewed by 32986

Special Issue Editors


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Guest Editor
Tumor and Breast Center ZeTuP St. Gallen, Rorschacherstr. 150, 9006 St. Gallen, Switzerland
Interests: medical oncology; drug resistance; marine anti-cancer compounds; drug development; tumor biology; proteomics
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
1. Laboratory of Experimental Oncology, Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
2. Martini-Klinik, Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany
Interests: marine natural compounds; secondary metabolites; anticancer activity; mechanism of action; autophagy; drug combinational studies
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In 2016, the Nobel Prize in Physiology or Medicine has been awarded to Prof. Yoshinori Ohsumi for the discoveries of mechanisms of autophagy. Autophagy is a basic physiological process, which has only recently received a lot of attention. This cellular process, which is implicated in many aspects of human physiology and disease, including tissue homeostasis, cancer, neurodegenerative conditions (Parkinson's and Alzheimer's disease), cardiomyopathy, and others, is essential for the survival and death of mammalian cells. Thus, it is an exciting perspective to find and develop compounds that have the ability to control and modify this process.
Lysosomes are an essential part of the autophagy machinery which plays a role at the final stages of this process, providing the degradation of the autophagosomes content. Furthermore, lysosomes participate in a vast number of physiological and pathological processes, and may play a role in both drug sensitivity and drug resistance. Several clinically approved compounds target lysosomes as their mode of action.
Compared to terrestrial life forms, marine inhabitants are by far less well studied organisms. At the same time, due to the extreme environmental conditions (high pressure, lack of light, salinity, pH), they harbor a unique variety of chemical compounds, of which a large number still await discovery and characterization. A good proportion of these compounds exhibit potent biological activity, targeting one or several specific biological processes.
This Special Issue “Marine Compounds as Modulators of Autophagy and Lysosomal Activity” in Marine Drugs will cover the whole scope of agents targeting autophagy or/and lysosomes both in vitro and in vivo – novel to previously characterized, including already clinically used marine derived compounds. This Special issue is focused on (but not limited to!) compounds that affect autophagy and lysosomes in malignant cells. In particular, the issue will collect work on compounds that are able to target lysosomes and modulate all the different types of autophagy – i.e. macroautophagy, microautophagy, and chaperone-mediated autophagy – with cytotoxic, cytoprotective, pro-survival, or non-cytotoxic biological activity.
Since autophagy is a relatively new and sometimes still controversial topic, results of similar experiments are often interpreted in different ways. Therefore, the Guest Editors suggest to use the recommendations recently described by Klionsky et al. in the “Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)” (Autophagy. 2016;12(1):1-222; PMID: 26799652) for interpretation of experimental data submitted to this Special Issue.

Sergey A. Dyshlovoy
Friedemann Honecker,
Guest Editors

Keywords

  • autophagy

  • macroautophagy

  • lysosomes

  • lysosomal membrane permeabilization (LMP)

  • cathepsins

  • marine compounds

  • cell death

  • cell survival

  • drug resistance

  • necrosis

  • cancer

  • neurodegenerative disease

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Published Papers (5 papers)

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Editorial

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3 pages, 161 KiB  
Editorial
Marine Compounds and Autophagy: Beginning of a New Era
by Sergey A. Dyshlovoy and Friedemann Honecker
Mar. Drugs 2018, 16(8), 260; https://doi.org/10.3390/md16080260 - 31 Jul 2018
Cited by 3 | Viewed by 2982
(This article belongs to the Special Issue Marine Compounds as Modulators of Autophagy and Lysosomal Activity)

Research

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20 pages, 4926 KiB  
Article
ATG5 Promotes Death Signaling in Response to the Cyclic Depsipeptides Coibamide A and Apratoxin A
by Xuemei Wan, Jeffrey D. Serrill, Ian R. Humphreys, Michelle Tan, Kerry L. McPhail, Ian G. Ganley and Jane E. Ishmael
Mar. Drugs 2018, 16(3), 77; https://doi.org/10.3390/md16030077 - 1 Mar 2018
Cited by 22 | Viewed by 6152
Abstract
Our understanding of autophagy and lysosomal function has been greatly enhanced by the discovery of natural product structures that can serve as chemical probes to reveal new patterns of signal transduction in cells. Coibamide A is a cytotoxic marine natural product that induces [...] Read more.
Our understanding of autophagy and lysosomal function has been greatly enhanced by the discovery of natural product structures that can serve as chemical probes to reveal new patterns of signal transduction in cells. Coibamide A is a cytotoxic marine natural product that induces mTOR-independent autophagy as an adaptive stress response that precedes cell death. Autophagy-related (ATG) protein 5 (ATG5) is required for coibamide-induced autophagy but not required for coibamide-induced apoptosis. Using wild-type and autophagy-deficient mouse embryonic fibroblasts (MEFs) we demonstrate that coibamide-induced toxicity is delayed in ATG5−/− cells relative to ATG5+/+ cells. Time-dependent changes in annexin V staining, membrane integrity, metabolic capacity and caspase activation indicated that MEFs with a functional autophagy pathway are more sensitive to coibamide A. This pattern could be distinguished from autophagy modulators that induce acute ER stress (thapsigargin, tunicamycin), ATP depletion (oligomycin A) or mTORC1 inhibition (rapamycin), but was shared with the Sec61 inhibitor apratoxin A. Coibamide- or apratoxin-induced cell stress was further distinguished from the action of thapsigargin by a pattern of early LC3-II accumulation in the absence of CHOP or BiP expression. Time-dependent changes in ATG5-ATG12, PARP1 and caspase-3 expression patterns were consistent with the conversion of ATG5 to a pro-death signal in response to both compounds. Full article
(This article belongs to the Special Issue Marine Compounds as Modulators of Autophagy and Lysosomal Activity)
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3978 KiB  
Article
Quantitative Proteomic Profiling of Tachyplesin I Targets in U251 Gliomaspheres
by Xuan Li, Jianguo Dai, Yongjun Tang, Lulu Li and Gang Jin
Mar. Drugs 2017, 15(1), 20; https://doi.org/10.3390/md15010020 - 18 Jan 2017
Cited by 19 | Viewed by 6712
Abstract
Tachyplesin I is a cationic peptide isolated from hemocytes of the horseshoe crab and its anti-tumor activity has been demonstrated in several tumor cells. However, there is limited information providing the global effects and mechanisms of tachyplesin I on glioblastoma multiforme (GBM). Here, [...] Read more.
Tachyplesin I is a cationic peptide isolated from hemocytes of the horseshoe crab and its anti-tumor activity has been demonstrated in several tumor cells. However, there is limited information providing the global effects and mechanisms of tachyplesin I on glioblastoma multiforme (GBM). Here, by using two complementary proteomic strategies (2D-DIGE and dimethyl isotope labeling-based shotgun proteomics), we explored the effect of tachyplesin I on the proteome of gliomaspheres, a three-dimensional growth model formed by a GBM cell line U251. In total, the expression levels of 192 proteins were found to be significantly altered by tachyplesin I treatment. Gene ontology (GO) analysis revealed that many of them were cytoskeleton proteins and lysosomal acid hydrolases, and the mostly altered biological process was related to cellular metabolism, especially glycolysis. Moreover, we built protein–protein interaction network of these proteins and suggested the important role of DNA topoisomerase 2-alpha (TOP2A) in the signal-transduction cascade of tachyplesin I. In conclusion, we propose that tachyplesin I might down-regulate cathepsins in lysosomes and up-regulate TOP2A to inhibit migration and promote apoptosis in glioma, thus contribute to its anti-tumor function. Our results suggest tachyplesin I is a potential candidate for treatment of glioma. Full article
(This article belongs to the Special Issue Marine Compounds as Modulators of Autophagy and Lysosomal Activity)
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1912 KiB  
Article
Tumor Protein (TP)-p53 Members as Regulators of Autophagy in Tumor Cells upon Marine Drug Exposure
by Edward A. Ratovitski
Mar. Drugs 2016, 14(8), 154; https://doi.org/10.3390/md14080154 - 16 Aug 2016
Cited by 28 | Viewed by 7370
Abstract
Targeting autophagic pathways might play a critical role in designing novel chemotherapeutic approaches in the treatment of human cancers, and the prevention of tumor-derived chemoresistance. Marine compounds were found to decrease tumor cell growth in vitro and in vivo. Some of them were [...] Read more.
Targeting autophagic pathways might play a critical role in designing novel chemotherapeutic approaches in the treatment of human cancers, and the prevention of tumor-derived chemoresistance. Marine compounds were found to decrease tumor cell growth in vitro and in vivo. Some of them were shown to induce autophagic flux in tumor cells. In this study, we observed that the selected marine life-derived compounds (Chromomycin A2, Psammaplin A, and Ilimaquinone) induce expression of several autophagic signaling intermediates in human squamous cell carcinoma, glioblastoma, and colorectal carcinoma cells in vitro through a transcriptional regulation by tumor protein (TP)-p53 family members. These conclusions were supported by specific qPCR expression analysis, luciferase reporter promoter assay, and chromatin immunoprecipitation of promoter sequences bound to the TP53 family proteins, and silencing of the TP53 members in tumor cells. Full article
(This article belongs to the Special Issue Marine Compounds as Modulators of Autophagy and Lysosomal Activity)
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Review

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1353 KiB  
Review
Blue-Print Autophagy: Potential for Cancer Treatment
by Nadia Ruocco, Susan Costantini and Maria Costantini
Mar. Drugs 2016, 14(7), 138; https://doi.org/10.3390/md14070138 - 21 Jul 2016
Cited by 30 | Viewed by 8839
Abstract
The marine environment represents a very rich source of biologically active compounds with pharmacological applications. This is due to its chemical richness, which is claiming considerable attention from the health science communities. In this review we give a general overview on the marine [...] Read more.
The marine environment represents a very rich source of biologically active compounds with pharmacological applications. This is due to its chemical richness, which is claiming considerable attention from the health science communities. In this review we give a general overview on the marine natural products involved in stimulation and inhibition of autophagy (a type of programmed cell death) linked to pharmacological and pathological conditions. Autophagy represents a complex multistep cellular process, wherein a double membrane vesicle (the autophagosome) captures organelles and proteins and delivers them to the lysosome. This natural and destructive mechanism allows the cells to degrade and recycle its cellular components, such as amino acids, monosaccharides, and lipids. Autophagy is an important mechanism used by cells to clear pathogenic organism and deal with stresses. Therefore, it has also been implicated in several diseases, predominantly in cancer. In fact, pharmacological stimulation or inhibition of autophagy have been proposed as approaches to develop new therapeutic treatments of cancers. In conclusion, this blue-print autophagy (so defined because it is induced and/or inhibited by marine natural products) represents a new strategy for the future of biomedicine and of biotechnology in cancer treatment. Full article
(This article belongs to the Special Issue Marine Compounds as Modulators of Autophagy and Lysosomal Activity)
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