Special Issue "Marine Natural Products as Anticancer Agents"

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

Deadline for manuscript submissions: 15 July 2021.

Special Issue Editors

Dr. Celso Alves
E-Mail Website
Guest Editor
MARE - Marine and Environmental Sciences Centre, Polytechnic of Leiria, 2520-630, Peniche, Portugal
Interests: marine natural products; biotechnological applications; pharmaceutical applications; signal transduction; anticancer activities; compounds isolation
Prof. Dr. Marc Diederich
E-Mail Website1 Website2
Guest Editor
Department of Pharmacy, College of Pharmacy, Seoul National University, Building 29 Room 223, 1 Gwanak-ro, Gwanak-gu Seoul, 08826, South Korea
Interests: oncology; signal transduction; cell death; inflammation
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Despite the advances concerning cancer biology and its therapeutic strategies achieved in the last decades, cancer remains a huge threat for human health, and one of the deadliest diseases worldwide. One of the main factors contributing to the high cancer mortality is related to therapy failure and consequent cancer relapse; thus it is of the utmost importance to develop innovative therapeutics strategies, including new drugs. In this field, marine natural products have revealed uncommon and rare chemical features, not found in the terrestrial environment, on which the molecular modelling and chemical synthesis of novel anticancer drugs can be inspired. As these compounds were produced in co-evolution with biological systems, they present greater an efficiency and specificity for interacting with biological target sites, exhibiting novel mechanisms of action and the ability to modulate distinct intracellular signaling pathways.

The focus of this Special Issue will be to highlight the potential of marine natural products as anticancer agents, empathizing the diversity of the molecular targets and the mechanistic effects. The application of innovative scientific approaches, including co-cultures and 3D culture models, to avoid the gap between in vitro and in vivo experiments is encouraged. Approaches describing synergistic combination treatments of marine compounds with clinically-used or experimental anticancer agents are welcome.

As compounds with anticancer immune modulatory functions are well-known, publications describing the cancer activity of such marine compounds alone or in combination with checkpoint inhibitors are encouraged to be submitted.

For this Special Issue, we invite academic and industry scientists to submit reviews and original and conceptual research articles highlighting the biological activities of known or novel marine compounds with a potential anticancer activity.

Dr. Celso Alves
Prof. Dr. Marc Diederich
Guest Editors

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 2400 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

  • anticancer
  • anti-tumor
  • immune
  • molecular targets
  • co-cultures
  • 3D culture models
  • marine natural products

Published Papers (8 papers)

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Research

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Open AccessCommunication
Optimization of Two Steps in Scale-Up Synthesis of Nannocystin A
Mar. Drugs 2021, 19(4), 198; https://doi.org/10.3390/md19040198 - 31 Mar 2021
Viewed by 236
Abstract
We have accomplished a 10-step (longest linear) total synthesis of nannocystin A on a four hundred milligram scale. The previously reported Kobayashi vinylogous Mukaiyama aldol reaction to connect C4 and C5 was unreproducible during the scaling up process. A more convenient and cost-efficient [...] Read more.
We have accomplished a 10-step (longest linear) total synthesis of nannocystin A on a four hundred milligram scale. The previously reported Kobayashi vinylogous Mukaiyama aldol reaction to connect C4 and C5 was unreproducible during the scaling up process. A more convenient and cost-efficient Keck asymmetric vinylogous aldol reaction was employed to improve this transformation. Full article
(This article belongs to the Special Issue Marine Natural Products as Anticancer Agents)
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Open AccessArticle
Astaxanthin Reduces Stemness Markers in BT20 and T47D Breast Cancer Stem Cells by Inhibiting Expression of Pontin and Mutant p53
Mar. Drugs 2020, 18(11), 577; https://doi.org/10.3390/md18110577 - 20 Nov 2020
Viewed by 568
Abstract
Astaxanthin (AST) is a product made from marine organisms that has been used as an anti-cancer supplement. It reduces pontin expression and induces apoptosis in SKBR3, a breast cancer cell line. Using Western blotting and qRT-PCR analyses, this study revealed that in the [...] Read more.
Astaxanthin (AST) is a product made from marine organisms that has been used as an anti-cancer supplement. It reduces pontin expression and induces apoptosis in SKBR3, a breast cancer cell line. Using Western blotting and qRT-PCR analyses, this study revealed that in the T47D and BT20 breast cancer cell lines, AST inhibits expression of pontin and mutp53, as well as the Oct4 and Nanog cancer stem cell (CSC) stemness genes. In addition, we explored the mechanism by which AST eradicates breast cancer cells using pontin siRNAs. Pontin knockdown by pontin siRNA reduced proliferation, Oct4 and Nanog expression, colony and spheroid formation, and migration and invasion abilities in breast cancer cells. In addition, reductions in Oct4, Nanog, and mutp53 expression following rottlerin treatment confirmed the role of pontin in these cells. Therefore, pontin may play a central role in the regulation of CSC properties and in cell proliferation following AST treatment. Taken together, these findings demonstrate that AST can repress CSC stemness genes in breast cancer cells, which implies that AST therapy could be used to improve the efficacy of other anti-cancer therapies against breast cancer cells. Full article
(This article belongs to the Special Issue Marine Natural Products as Anticancer Agents)
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Open AccessArticle
Marine-Derived Penicillium purpurogenum Reduces Tumor Size and Ameliorates Inflammation in an Erlich Mice Model
Mar. Drugs 2020, 18(11), 541; https://doi.org/10.3390/md18110541 - 29 Oct 2020
Viewed by 586
Abstract
Background: This study addresses the antitumoral properties of Penicillium purpurogenum isolated from a polluted lagoon in Northeastern Brazil. Methods: Ethyl Acetate Extracellular Extract (EAE) was used. The metabolites were studied using direct infusion mass spectrometry. The solid Ehrlich tumor model was used for [...] Read more.
Background: This study addresses the antitumoral properties of Penicillium purpurogenum isolated from a polluted lagoon in Northeastern Brazil. Methods: Ethyl Acetate Extracellular Extract (EAE) was used. The metabolites were studied using direct infusion mass spectrometry. The solid Ehrlich tumor model was used for antitumor activity. Female Swiss mice were divided into groups (n = 10/group) as follows: The negative control (CTL−), treated with a phosphate buffered solution; the positive control (CTL+), treated with cyclophosphamide (25 mg/kg); extract treatments at doses of 4, 20, and 100 mg/kg; animals without tumors or treatments (Sham); and animals without tumors treated with an intermediate dose (EAE20). All treatments were performed intraperitoneally, daily, for 15 days. Subsequently, the animals were euthanized, and the tumor, lymphoid organs, and serum were used for immunological, histological, and biochemical parameter evaluations. Results: The extract was rich in meroterpenoids. All doses significantly reduced tumor size, and the 20 and 100 mg/kg doses reduced tumor-associated inflammation and tumor necrosis. The extract also reduced the cellular infiltration of lymphoid organs and circulating TNF-α levels. The extract did not induce weight loss or renal and hepatic toxic changes. Conclusions: These results indicate that P. purpurogenum exhibits immunomodulatory and antitumor properties in vivo. Thus, fungal fermentation is a valid biotechnological approach to the production of antitumor agents. Full article
(This article belongs to the Special Issue Marine Natural Products as Anticancer Agents)
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Open AccessArticle
New Biscembranoids Sardigitolides A–D and Known Cembranoid-Related Compounds from Sarcophyton digitatum: Isolation, Structure Elucidation, and Bioactivities
Mar. Drugs 2020, 18(9), 452; https://doi.org/10.3390/md18090452 - 29 Aug 2020
Cited by 2 | Viewed by 866
Abstract
Chemical examination from the cultured soft coral Sarcophyton digitatum resulted in the isolation and structural identification of four new biscembranoidal metabolites, sardigitolides A–D (14), along with three previously isolated biscembranoids, sarcophytolide L (5), glaucumolide A (6 [...] Read more.
Chemical examination from the cultured soft coral Sarcophyton digitatum resulted in the isolation and structural identification of four new biscembranoidal metabolites, sardigitolides A–D (14), along with three previously isolated biscembranoids, sarcophytolide L (5), glaucumolide A (6), glaucumolide B (7), and two known cembranoids (8 and 9). The chemical structures of all isolates were elucidated on the basis of 1D and 2D NMR spectroscopic analyses. Additionally, in order to discover bioactivity of marine natural products, 18 were examined in terms of their inhibitory potential against the upregulation of inflammatory factor production in lipopolysaccharide (LPS)-stimulated murine macrophage J774A.1 cells and their cytotoxicities against a limited panel of cancer cells. The anti-inflammatory results showed that at a concentration of 10 µg/mL, 6 and 8 inhibited the production of IL-1β to 68 ± 1 and 56 ± 1%, respectively, in LPS-stimulated murine macrophages J774A.1. Furthermore, sardigitolide B (2) displayed cytotoxicities toward MCF-7 and MDA-MB-231 cancer cell lines with the IC50 values of 9.6 ± 3.0 and 14.8 ± 4.0 µg/mL, respectively. Full article
(This article belongs to the Special Issue Marine Natural Products as Anticancer Agents)
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Open AccessArticle
Anti-Tumor Effects of Astaxanthin by Inhibition of the Expression of STAT3 in Prostate Cancer
Mar. Drugs 2020, 18(8), 415; https://doi.org/10.3390/md18080415 - 07 Aug 2020
Cited by 1 | Viewed by 926
Abstract
Astaxanthin is a natural product gaining increasing attention due to its safety and anti-cancer properties. In this study, we investigated the mechanisms of the anti-cancer effects of astaxanthin on prostate cancer (PCa) cell lines using aggressive PCa DU145 cells. Also an instantaneous silenced [...] Read more.
Astaxanthin is a natural product gaining increasing attention due to its safety and anti-cancer properties. In this study, we investigated the mechanisms of the anti-cancer effects of astaxanthin on prostate cancer (PCa) cell lines using aggressive PCa DU145 cells. Also an instantaneous silenced cell line (si-STAT3) derived from DU145 and a control cell line (si-NK) were used for the MTT and colony formation assays to determine the role of astaxanthin in proliferation and colony formation abilities. Flow cytometry assays were used to detect the apoptosis of tumor cells. Migration and invasion assays detected the weakening of the respective abilities. Western blot and RT-PCR tests detected the levels of STAT3 protein and mRNA. Astaxanthin resulted in suppression of the proliferation of DU145 cells and the level of STAT3. The treatment of DU145 cells with astaxanthin decreased the cloning ability, increased the apoptosis percentage and weakened the abilities of migration and invasion of the cells. Furthermore, astaxanthin reduced the expression of STAT3 at protein and mRNA levels. The effects were enhanced when astaxanthin and si-STAT3 were combined. The results of animal experiments were consistent with the results in cells. Thus, astaxanthin inhibits the proliferation of DU145 cells by reducing the expression of STAT3. Full article
(This article belongs to the Special Issue Marine Natural Products as Anticancer Agents)
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Open AccessArticle
Exploring the Mechanism of Flaccidoxide-13-Acetate in Suppressing Cell Metastasis of Hepatocellular Carcinoma
Mar. Drugs 2020, 18(6), 314; https://doi.org/10.3390/md18060314 - 15 Jun 2020
Viewed by 760
Abstract
Hepatocellular carcinoma (HCC) is the most common liver or hepatic cancer, accounting for 80% of all cases. The majority of this cancer mortality is due to metastases, rather than orthotopic tumors. Therefore, the inhibition of tumor metastasis is widely recognized as the key [...] Read more.
Hepatocellular carcinoma (HCC) is the most common liver or hepatic cancer, accounting for 80% of all cases. The majority of this cancer mortality is due to metastases, rather than orthotopic tumors. Therefore, the inhibition of tumor metastasis is widely recognized as the key strategy for successful intervention. A cembrane-type diterpene, flaccidoxide-13-acetate, isolated from marine soft coral Sinularia gibberosa, has been reported to have inhibitory effects against RT4 and T24 human bladder cancer invasion and cell migration. In this study, we investigated its suppression effects on tumor growth and metastasis of human HCC, conducting Boyden chamber and Transwell assays using HA22T and HepG2 human HCC cell lines to evaluate invasion and cell migration. We utilized gelatin zymography to determine the enzyme activities of matrix metalloproteinases MMP-2 and MMP-9. We also analyzed the expression levels of MMP-2 and MMP-9. Additionally, assays of tissue inhibitors of metalloproteinase-1/2 (TIMP-1/2), the focal adhesion kinase (FAK)/phosphatidylinositide-3 kinases (PI3K)/Akt/mammalian target of the rapamycin (mTOR) signaling pathway, and the epithelial-mesenchymal transition (EMT) process were performed. We observed that flaccidoxide-13-acetate could potentially inhibit HCC cell migration and invasion. We postulated that, by inhibiting the FAK/PI3K/Akt/mTOR signaling pathway, MMP-2 and MMP-9 expressions were suppressed, resulting in HCC cell metastasis. Flaccidoxide-13-acetate was found to inhibit EMT in HA22T and HepG2 HCC cells. Our study results suggested the potential of flaccidoxide-13-acetate as a chemotherapeutic candidate; however, its clinical application for the management of HCC in humans requires further research. Full article
(This article belongs to the Special Issue Marine Natural Products as Anticancer Agents)
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Open AccessArticle
Cytotoxic Secondary Metabolites Isolated from the Marine Alga-Associated Fungus Penicillium chrysogenum LD-201810
Mar. Drugs 2020, 18(5), 276; https://doi.org/10.3390/md18050276 - 22 May 2020
Viewed by 886
Abstract
A new pentaketide derivative, penilactonol A (1), and two new hydroxyphenylacetic acid derivatives, (2’R)-stachyline B (2) and (2’R)-westerdijkin A (3), together with five known metabolites, bisabolane-type sesquiterpenoids 46 and meroterpenoids 7 [...] Read more.
A new pentaketide derivative, penilactonol A (1), and two new hydroxyphenylacetic acid derivatives, (2’R)-stachyline B (2) and (2’R)-westerdijkin A (3), together with five known metabolites, bisabolane-type sesquiterpenoids 46 and meroterpenoids 7 and 8, were isolated from the solid culture of a marine alga-associated fungus Penicillium chrysogenum LD-201810. Their structures were elucidated based on extensive spectroscopic analyses, including 1D/2D NMR and high resolution electrospray ionization mass spectra (HRESIMS). The absolute configurations of the stereogenic carbons in 1 were determined by the (Mo2(OAc)4)-induced circular dichroism (CD) and comparison of the calculated and experimental electronic circular dichroism (ECD) spectra, while the absolute configuration of the stereogenic carbon in 2 was established using single-crystal X-ray diffraction analysis. Compounds 2 and 3 adapt the 2’R-configuration as compared to known hydroxyphenylacetic acid-derived and O-prenylated natural products. The cytotoxicity of 18 against human carcinoma cell lines (A549, BT-549, HeLa, HepG2, MCF-7, and THP-1) was evaluated. Compound 3 exhibited cytotoxicity to the HepG2 cell line with an IC50 value of 22.0 μM. Furthermore, 5 showed considerable activities against A549 and THP-1 cell lines with IC50 values of 21.2 and 18.2 μM, respectively. Full article
(This article belongs to the Special Issue Marine Natural Products as Anticancer Agents)
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Review

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Open AccessReview
Marine-Derived Secondary Metabolites as Promising Epigenetic Bio-Compounds for Anticancer Therapy
Mar. Drugs 2021, 19(1), 15; https://doi.org/10.3390/md19010015 - 31 Dec 2020
Viewed by 710
Abstract
Sessile organisms such as seaweeds, corals, and sponges continuously adapt to both abiotic and biotic components of the ecosystem. This extremely complex and dynamic process often results in different forms of competition to ensure the maintenance of an ecological niche suitable for survival. [...] Read more.
Sessile organisms such as seaweeds, corals, and sponges continuously adapt to both abiotic and biotic components of the ecosystem. This extremely complex and dynamic process often results in different forms of competition to ensure the maintenance of an ecological niche suitable for survival. A high percentage of marine species have evolved to synthesize biologically active molecules, termed secondary metabolites, as a defense mechanism against the external environment. These natural products and their derivatives may play modulatory roles in the epigenome and in disease-associated epigenetic machinery. Epigenetic modifications also represent a form of adaptation to the environment and confer a competitive advantage to marine species by mediating the production of complex chemical molecules with potential clinical implications. Bioactive compounds are able to interfere with epigenetic targets by regulating key transcriptional factors involved in the hallmarks of cancer through orchestrated molecular mechanisms, which also establish signaling interactions of the tumor microenvironment crucial to cancer phenotypes. In this review, we discuss the current understanding of secondary metabolites derived from marine organisms and their synthetic derivatives as epigenetic modulators, highlighting advantages and limitations, as well as potential strategies to improve cancer treatment. Full article
(This article belongs to the Special Issue Marine Natural Products as Anticancer Agents)
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