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Marine Drugs
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Development and Application of Marine-Derived Anti-cancer Agents
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Development and Application of Marine-Derived Anti-cancer Agents

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

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 15649

Special Issue Editor

Dr. Raimundo Gonçalves de Oliveira Junior

E-Mail Website
Guest Editor
UMR 8038 CiTCoM, Faculté de Santé, UFR Pharmacie, Université Paris Cité, 75006 Paris, France
Interests: marine natural products; anticancer; pigments; microalgae; chemosensitization
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Marine organisms are known to synthesize a diversity of molecules with unique structural skeletons and remarkable applications in the pharmaceutical, food, and cosmetic industries. Marine-derived bioactive compounds include polysaccharides, sterols, proteins, polyunsaturated fatty acids (PUFAs), pigments, etc. These compounds are capable of inhibiting cell growth and migration, inducing cell cycle arrest and apoptosis, and restoring the sensitivity of tumor cells to conventional anticancer drugs. In recent decades, the use of marine compounds in combination with classical cytotoxic agents has emerged as a new approach to circumvent tumor resistance mechanisms.

Despite their undeniable anticancer potential, limiting factors have hindered the clinical use of marine natural products, such as the development of ecofriendly scaled-up extraction and purification processes and the lack of solid preclinical data.

In this Special Issue, we invite you to publish reviews or original articles dealing with, but not limited to, the following topics:

  • Extraction, isolation, and characterization;
  • Metabolomic profile of marine-derived products;
  • Scaled-up extraction and purification methods;
  • Ecofriendly strategies to obtain anticancer compounds;
  • Anticancer activity of extracts, enriched fractions, or isolated compounds;
  • Innovative mechanisms of action;
  • Marine natural products as chemosensitizing agents;
  • Toxicological and pharmacokinetic investigations;
  • Technological development of new marine-based formulations.

Dr. Raimundo Gonçalves de Oliveira Junior
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

  • anticancer molecules
  • marine biotechnology
  • tumor sensitization
  • drug discovery
  • ecofriendly extraction and purification
  • secondary metabolites
  • multidrug resistance

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Further information on MDPI's Special Issue polices can be found here.

Published Papers (5 papers)

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Research

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17 pages, 2605 KiB  
Article
Stellettin B Induces Cell Death in Bladder Cancer Via Activating the Autophagy/DAPK2/Apoptosis Signaling Cascade
by Chun-Han Chang, Bo-Jyun Lin, Chun-Han Chen, Nham-Linh Nguyen, Tsung-Han Hsieh, Jui-Hsin Su and Mei-Chuan Chen
Mar. Drugs 2023, 21(2), 73; https://doi.org/10.3390/md21020073 - 21 Jan 2023
Cited by 9 | Viewed by 2791
Abstract
Bladder cancer (BC) is one of the most prevalent cancers worldwide. However, the recurrence rate and five-year survival rate have not been significantly improved in advanced BC, and new therapeutic strategies are urgently needed. The anticancer activity of stellettin B (SP-2), a triterpene [...] Read more.
Bladder cancer (BC) is one of the most prevalent cancers worldwide. However, the recurrence rate and five-year survival rate have not been significantly improved in advanced BC, and new therapeutic strategies are urgently needed. The anticancer activity of stellettin B (SP-2), a triterpene isolated from the marine sponge Rhabdastrella sp., was evaluated with the MTT assay as well as PI and Annexin V/7-AAD staining. Detailed mechanisms were elucidated through an NGS analysis, protein arrays, and Western blotting. SP-2 suppressed the viability of BC cells without severe toxicity towards normal uroepithelial cells, and it increased apoptosis with the activation of caspase 3/8/9, PARP, and γH2AX. The phosphorylation of FGFR3 and its downstream targets were downregulated by SP-2. Meanwhile, it induced autophagy in BC cells as evidenced by LC3-II formation and p62 downregulation. The inhibition of autophagy using pharmacological inhibitors or through an ATG5-knockout protected RT-112 cells from SP-2-induced cell viability suppression and apoptosis. In addition, the upregulation of DAPK2 mRNA and protein expression also contributed to SP-2-induced cytotoxicity and apoptosis. In RT-112 cells, an FGFR3-TACC3-knockout caused the downregulation of DAPK2, autophagy, and apoptosis. In conclusion, this is the first study demonstrating that SP-2 exhibits potent anti-BC activity by suppressing the FGFR3-TACC3/Akt/mTOR pathway, which further activates a novel autophagy/DAPK2/apoptosis signaling cascade. Full article
(This article belongs to the Special Issue Development and Application of Marine-Derived Anti-cancer Agents)
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20 pages, 6016 KiB  
Article
Therapeutic Potential of Microalgae-Derived Bioactive Metabolites Is Influenced by Different Large-Scale Culture Strategies
by Jezabel Garcia-Parra, Claudio Fuentes-Grünewald and Deyarina Gonzalez
Mar. Drugs 2022, 20(10), 627; https://doi.org/10.3390/md20100627 - 30 Sep 2022
Cited by 4 | Viewed by 3099
Abstract
Microalgae have been identified as one of the most promising sources of novel bioactive compounds for biomedical applications, the food industry, and cosmetics. In the last decade, several biotechnological developments have facilitated the identification of a growing number of compounds as well as [...] Read more.
Microalgae have been identified as one of the most promising sources of novel bioactive compounds for biomedical applications, the food industry, and cosmetics. In the last decade, several biotechnological developments have facilitated the identification of a growing number of compounds as well as the study of optimal microalgae culture conditions for the production of biomass enriched in specific molecules of interest. In this study, two common commercial marine microalgae (Nannochloropsis oculata and Porphyridium purpureum) were cultured in standard and nutrient-stressed conditions and the obtained biomass extracts were assessed for their potential to inhibit cancer cell proliferation and migration as well as their antioxidant activity. Results from viability in 2D and 3D cancer cell models showed an enhancement of the antitumour activity of P. purpureum in the 3D model compared to 2D, together with a greater capacity to reduce the migration capacity of cancer cells with the biomass from nutrient-stressed conditions, whereas the antioxidant activity of N. oculata decreased when exposed to nutrient-stressed conditions. To date, this is one of the few studies that proves that controlled changes in large-scale culturing conditions such as nutrient depletion have a relevant impact in the bioactivity of the biomass on cancer cells. Full article
(This article belongs to the Special Issue Development and Application of Marine-Derived Anti-cancer Agents)
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21 pages, 5132 KiB  
Article
Ilimaquinone (Marine Sponge Metabolite) Induces Apoptosis in HCT-116 Human Colorectal Carcinoma Cells via Mitochondrial-Mediated Apoptosis Pathway
by Malvi Surti, Mitesh Patel, Alya Redhwan, Lamya Ahmed Al-Keridis, Mohd Adnan, Nawaf Alshammari and Mandadi Narsimha Reddy
Mar. Drugs 2022, 20(9), 582; https://doi.org/10.3390/md20090582 - 18 Sep 2022
Cited by 10 | Viewed by 2709
Abstract
Ilimaquinone (IQ), a metabolite found in marine sponges, has been reported to have a number of biological properties, including potential anticancer activity against colon cancer. However, no clear understanding of the precise mechanism involved is known. The aim of this study was to [...] Read more.
Ilimaquinone (IQ), a metabolite found in marine sponges, has been reported to have a number of biological properties, including potential anticancer activity against colon cancer. However, no clear understanding of the precise mechanism involved is known. The aim of this study was to examine the molecular mechanism by which IQ acts on HCT-116 cells. The anticancer activity of IQ was investigated by means of a cell viability assay followed by the determination of induction of apoptosis by means of the use of acridine orange–ethidium bromide (AO/EB) staining, Annexin V/PI double staining, DNA fragmentation assays, and TUNEL assays. The mitochondrial membrane potential (ΔΨm) was detected using the JC-1 staining technique, and the apoptosis-associated proteins were analyzed using real-time qRT-PCR. A molecular docking study of IQ with apoptosis-associated proteins was also conducted in order to assess the interaction between IQ and them. Our results suggest that IQ significantly suppressed the viability of HCT-116 cells in a dose-dependent manner. Fluorescent microscopy, flow cytometry, DNA fragmentation and the TUNEL assay in treated cells demonstrated apoptotic death mode. As an additional confirmation of apoptosis, the increased level of caspase-3 and caspase-9 expression and the downregulation of Bcl-2 and mitochondrial dysfunction were observed in HCT-116 cells after treatment with IQ, which was accompanied by a decrease in mitochondrial membrane potential (ΔΨm). Overall, the results of our studies demonstrate that IQ could trigger mitochondria-mediated apoptosis as demonstrated by a decrease in ΔΨm, activation of caspase-9/-3, damage of DNA and a decrease in the proportion of Bcl-2 through the mitochondrial-mediated apoptosis pathway. Full article
(This article belongs to the Special Issue Development and Application of Marine-Derived Anti-cancer Agents)
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21 pages, 4817 KiB  
Article
Heteronemin and Tetrac Induce Anti-Proliferation by Blocking EGFR-Mediated Signaling in Colorectal Cancer Cells
by Sukanya Unson, Tung-Cheng Chang, Yung-Ning Yang, Shwu-Huey Wang, Chi-Hung Huang, Dana R. Crawford, Haw-Ming Huang, Zi-Lin Li, Hung-Yun Lin, Jacqueline Whang-Peng, Kuan Wang, Paul J. Davis and Wen-Shan Li
Mar. Drugs 2022, 20(8), 482; https://doi.org/10.3390/md20080482 - 27 Jul 2022
Cited by 5 | Viewed by 3031
Abstract
Overexpressed EGFR and mutant K-Ras play vital roles in therapeutic resistance in colorectal cancer patients. To search for an effective therapeutic protocol is an urgent task. A secondary metabolite in the sponge Hippospongia sp., Heteronemin, has been shown to induce anti-proliferation in several [...] Read more.
Overexpressed EGFR and mutant K-Ras play vital roles in therapeutic resistance in colorectal cancer patients. To search for an effective therapeutic protocol is an urgent task. A secondary metabolite in the sponge Hippospongia sp., Heteronemin, has been shown to induce anti-proliferation in several types of cancers. A thyroxine-deaminated analogue, tetrac, binds to integrin αvβ3 to induce anti-proliferation in different cancers. Heteronemin- and in combination with tetrac-induced antiproliferative effects were evaluated. Tetrac enhanced heteronemin-induced anti-proliferation in HT-29 cells (KRAS WT CRC) and HCT-116 cells (KRAS MT CRC). Heteronemin and tetrac arrested cell cycle in different phases. Combined treatment increased the cell accumulation in sub-G1 and S phases. The combined treatment also induced the inactivation of EGFR signaling and downregulated the phosphorylated ERK1/2 protein in both cell lines. Heteronemin and the combination showed the downregulation of the phosphorylated and total PI3K protein in HT-29 cells (KRAS WT CRC). Results by NanoString technology and RT-qPCR revealed that heteronemin and combined treatment suppressed the expression of EGFR and downstream genes in HCT-116 cells (KRAS MT CRC). Heteronemin or combined treatment downregulated genes associated with cancer progression and decreased cell motility. Heteronemin or the combined treatment suppressed PD-L1 expression in both cancer cell lines. However, only tetrac and the combined treatment inhibited PD-L1 protein accumulation in HT-29 cells (KRAS WT CRC) and HCT-116 cells (KRAS MT CRC), respectively. In summary, heteronemin induced anti-proliferation in colorectal cancer cells by blocking the EGFR-dependent signal transduction pathway. The combined treatment further enhanced the anti-proliferative effect via PD-L1 suppression. It can be an alternative strategy to suppress mutant KRAS resistance for anti-EGFR therapy. Full article
(This article belongs to the Special Issue Development and Application of Marine-Derived Anti-cancer Agents)
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Review

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26 pages, 5906 KiB  
Review
Carotenoids from Marine Microalgae as Antimelanoma Agents
by Christiane Adrielly Alves Ferraz, Raphaël Grougnet, Elodie Nicolau, Laurent Picot and Raimundo Gonçalves de Oliveira Junior
Mar. Drugs 2022, 20(10), 618; https://doi.org/10.3390/md20100618 - 29 Sep 2022
Cited by 8 | Viewed by 3213
Abstract
Melanoma cells are highly invasive and metastatic tumor cells and commonly express molecular alterations that contribute to multidrug resistance (e.g., BRAFV600E mutation). Conventional treatment is not effective in a long term, requiring an exhaustive search for new alternatives. Recently, carotenoids from microalgae [...] Read more.
Melanoma cells are highly invasive and metastatic tumor cells and commonly express molecular alterations that contribute to multidrug resistance (e.g., BRAFV600E mutation). Conventional treatment is not effective in a long term, requiring an exhaustive search for new alternatives. Recently, carotenoids from microalgae have been investigated as adjuvant in antimelanoma therapy due to their safety and acceptable clinical tolerability. Many of them are currently used as food supplements. In this review, we have compiled several studies that show microalgal carotenoids inhibit cell proliferation, cell migration and invasion, as well as induced cell cycle arrest and apoptosis in various melanoma cell lines. MAPK and NF-ĸB pathway, MMP and apoptotic factors are frequently affected after exposure to microalgal carotenoids. Fucoxanthin, astaxanthin and zeaxanthin are the main carotenoids investigated, in both in vitro and in vivo experimental models. Preclinical data indicate these compounds exhibit direct antimelanoma effect but are also capable of restoring melanoma cells sensitivity to conventional chemotherapy (e.g., vemurafenib and dacarbazine). Full article
(This article belongs to the Special Issue Development and Application of Marine-Derived Anti-cancer Agents)
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