Special Issue "Antiproliferative Marine Natural Products Inducing Non-apoptotic Cell Death or Chemosentisizing Cancer Cells"

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

Deadline for manuscript submissions: 20 August 2020.

Special Issue Editor

Dr. Laurent Picot
Website
Guest Editor
Universite de La Rochelle, UMRi CNRS 7266 LIENSs, La Rochelle, France
Interests: anticancer compounds; heterocycles; melanoma; microalgae; natural products; pharmacology; pigments; tumor phototherapy

Special Issue Information

Dear Colleagues,

Despite major advances in the treatment of tumors, the cancer research community is still actively searching for new natural products with antiproliferative activity, which are able to overcome intrinsic or acquired chemotherapy resistance.

While for many years cytotoxic agents have been developed to target apoptotic cell death as a main method of treating cancer, with effective results in numerous tumor models, it is now widely recognized that evasion of apoptotic cell death is one of the characteristics of chemoresistant cancer cells. This suggests that identification of molecules targeting cell death pathways that are different from caspase-dependent intrinsic apoptosis (e.g., anoikis, autophagic cell death, cornification, entosis, mitotic catastrophe, necroptosis, netosis, parthanatos, pyroptosis, and ferroptosis) could offer novel cancer treatment options. There is also a growing interest for non-toxic and cytostatic natural products that are able to chemosensitize tumor cells to conventional cytotoxic drugs, thus limiting their toxic side effects and delaying the appearance of acquired chemoresistance.

Marine organisms represent a prolific potential source of antiproliferative natural products; the first marine drugs identified were potent cytotoxic and antiproliferative molecules. Since these pioneering works, thousands of molecules providing original chemical scaffolds and mechanisms of action have been discovered, and there is clear potential for a rapid expansion in marine drug developments in the next few decades. It is worth mentioning that among the marine molecules that have been approved as drugs, or have reached clinical trials, most of them are anticancer drugs disrupting molecular targets regulating DNA replication, cell cycle, cytoskeletal dynamics, or cytoplasmic membrane integrity. Furthermore, certain marine drugs exhibit original mechanisms of actions, targeting specific organelles or cellular processes. However, despite this promise, many limitations are yet to be overcome. These include the need to develop economically sustainable biotechnological or chemical production of bioactive compounds often limited by molecular complexity, the necessity to screen and investigate the pharmacological activity of identified compounds using diversified and relevant assays, and the need to study the ecophysiology of source species and the valorization of metagenomic data for non-cultivable organisms. 

In this Special Issue, we will explore all aspects of antiproliferative marine natural products inducing cell deaths that are different from caspase-dependent intrinsic apoptosis or chemosentisizing cancer cells to anticancer compounds, including chemical diversity within marine taxa, chemical ecology research aimed at understanding the natural function of these bioactive compounds, innovations in extraction, and the purification and structural elucidation of complex antiproliferative metabolites, as well as biotechnology developments dedicated to their sustainable production. We are also interested in highlighting innovative research that will enhance our understanding of the cellular and molecular pharmacology of these antiproliferative molecules, or discussing novel mechanisms of action and innovative therapeutic applications. Additionally, we will also emphasize research aimed at improving or accelerating the screening, chemical synthesis, and clinical development of these marine drugs exhibiting original modes of action.

As Guest Editor, I invite you to contribute to the Special Issue on “Antiproliferative Marine Natural products inducing non-apoptotic cell death or chemosentisizing cancer cells”. Original research reports and reviews will be published online in Marine Drugs.

Dr. Laurent Picot
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 papers will be 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 2000 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

  • biotechnology and metagenomics
  • cancer
  • chemical ecology
  • chemosensitization
  • mechanism of action
  • multidrug resistance
  • non-apoptotic cell death
  • organic synthesis and structural elucidation

Published Papers (3 papers)

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Research

Open AccessArticle
Fucosterol Suppresses the Progression of Human Ovarian Cancer by Inducing Mitochondrial Dysfunction and Endoplasmic Reticulum Stress
Mar. Drugs 2020, 18(5), 261; https://doi.org/10.3390/md18050261 - 16 May 2020
Abstract
Ovarian cancer is difficult to diagnose early and has high rates of relapse and mortality. Therefore, the treatment of ovarian cancer needs to be improved. Recently, several studies have been conducted in an attempt to develop anticancer drugs from naturally derived ingredients. Compared [...] Read more.
Ovarian cancer is difficult to diagnose early and has high rates of relapse and mortality. Therefore, the treatment of ovarian cancer needs to be improved. Recently, several studies have been conducted in an attempt to develop anticancer drugs from naturally derived ingredients. Compared to traditional chemotherapy, natural compounds can overcome drug resistance with lower side effects. Fucosterol, a phytosterol present in brown algae, reportedly possesses many bioactive effects, including anticancer properties. However, the anticancer effects of fucosterol in ovarian cancer remain unexplored. Therefore, we investigated the effects of fucosterol on progression in human ovarian cancer cells. Fucosterol inhibited cell proliferation and cell-cycle progression in ovarian cancer cells. Additionally, fucosterol regulated the proliferation-related signaling pathways, the production of reactive oxygen species, mitochondrial function, endoplasmic reticulum stress, angiogenesis, and calcium homeostasis. Moreover, it decreased tumor formation in a zebrafish xenograft model. These results indicate that fucosterol could be used as a potential therapeutic agent in ovarian cancer. Full article
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Open AccessArticle
K092A and K092B, Two Peptides Isolated from the Dogfish (Scyliorhinus canicula L.), with Potential Antineoplastic Activity Against Human Prostate and Breast Cancer Cells
Mar. Drugs 2019, 17(12), 672; https://doi.org/10.3390/md17120672 - 28 Nov 2019
Abstract
Cancer therapy is currently a major challenge within the research community, especially in reducing the side effects of treatments and to develop new specific strategies against cancers that still have a poor prognosis. In this context, alternative strategies using biotechnologies, such as marine [...] Read more.
Cancer therapy is currently a major challenge within the research community, especially in reducing the side effects of treatments and to develop new specific strategies against cancers that still have a poor prognosis. In this context, alternative strategies using biotechnologies, such as marine peptides, have been developed based on their promise of effectivity associated with a low toxicity for healthy cells. The purpose of the present paper is to investigate the active mechanism of two peptides that were isolated from the epigonal tissue of the lesser spotted dogfish Scyliorhinus canicula L., identified NFDTDEQALEDVFSKYG (K092A) and EAPPEAAEEDEW (K092B) on the in vitro growth inhibition of ZR-75-1 mammary carcinoma cells and MDA-Pca-2b prostate cancer cells. The effects of the peptides on cell proliferation and cell death mechanisms were studied by the flow cytometry and immunofluorescence microscopy approaches. The results have shown the onset of both K092A- and K092B-induced early cytoskeleton changes, and then cell cycle perturbations followed by non-apoptotic cell death. Moreover, impedance perturbation and plasma membrane perforation in ZR-75-1 K092A-treated cell cultures and autophagy inhibition in MDA-Pca-2b K092B-treated cells have been observed. In conclusion, these two bioactive peptides from dogfish exhibit antineoplastic activity on the human prostate and breast cancer cells in vitro. Full article
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Open AccessArticle
A Novel Mutant of rLj-RGD3 (rLj-112) Suppressed the Proliferation and Metastasis of B16 Cells through the EGFR Signaling Pathway
Mar. Drugs 2019, 17(2), 75; https://doi.org/10.3390/md17020075 - 23 Jan 2019
Abstract
Lj-RGD3, which contains three Arg–Gly–Asp (RGD) motifs, was first identified from the buccal glands of Lampetra japonica and has been shown to suppress the tumor progression in the previous studies. Apart from the three RGD motifs, Lj-RGD3 is also characterized by its high [...] Read more.
Lj-RGD3, which contains three Arg–Gly–Asp (RGD) motifs, was first identified from the buccal glands of Lampetra japonica and has been shown to suppress the tumor progression in the previous studies. Apart from the three RGD motifs, Lj-RGD3 is also characterized by its high content of histidine in its amino acid sequence. In order to clarify whether the histidine-rich characterization of Lj-RGD3 is also associated with its anti-tumor activity, mutants were designed in which the three RGD motifs (Lj-112), or all histidines (Lj-27) or both (Lj-26) were deleted. Furthermore, a mutant (Lj-42) in which all histidines and three RGD motifs were respectively substituted with alanines and three Ala–Gly–Asp (AGD) motifs, as well as a mutant (Lj-41) in which all histidines were substituted with alanines was synthesized to avoid alterations in structure which might further cause changes in the peptides’ functions. After recombination and purification, recombinant Lj-112 (rLj-112), recombinant Lj-27 (rLj-27), recombinant Lj-41 (rLj-41), and recombinant Lj-RGD3 (rLj-RGD3) exhibited anti-proliferative activity in B16 cells, respectively; while recombinant Lj-26 (rLj-26) and recombinant Lj-42 (rLj-42) did not affect the proliferation of B16 cells significantly. In addition, the anti-proliferative activity of rLj-112 in B16 cells was due to apoptosis. Typical apoptosis features were observed, including chromatin condensation, fragmented DNA, and increased levels of cleaved caspase 3/caspase 7/nuclear enzyme poly (ADP-ribose) polymerase (PARP) in B16 cells. Similar to rLj-RGD3, rLj-112 was also capable of suppressing the migration and invasion of B16 cells by disturbing the F-actin arrangement. After labeling with FITC, rLj-112 was found localized in the cytoplasm of B16 cells, which induced the internalization of epidermal growth factor receptor (EGFR), suggesting that rLj-112 might block the EGFR mediated signaling pathway. Actually, the phosphorylation level of EGFR and its downstream signal molecules including Akt, PI3K, p38, and ERK1/2 was reduced in the rLj-112 treated B16 cells. In vivo, rLj-112 also inhibited the growth, weight, and volume of the tumors in B16 xenografted C57BL/6 mice without reducing their body weight, indicating that rLj-112 might be safe and might be used as an effective anti-tumor drug in the near future. Full article
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