Marine Drugs

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Open AccessArticle

High-Level Expression, Purification and Large-Scale Production of l-Methionine γ-Lyase from Idiomarina as a Novel Anti-Leukemic Drug

by Kui-Ying Huang, Hai-Yan Hu, Yan-Lai Tang, Feng-Geng Xia, Xue-Qun Luo and Jian-Zhong Liu

Mar. Drugs 2015, 13(8), 5492-5507; https://doi.org/10.3390/md13085492 - 21 Aug 2015

Cited by 13 | Viewed by 6592

Abstract

l-Methionine γ-lyase (MGL), a pyridoxal 5′-phosphate-dependent enzyme, possesses anti-tumor activity. However, the low activity of MGL blocks the anti-tumor effect. This study describes an efficient production process for the recombinant MGL (rMGL) from Idiomarina constructed using the overexpression plasmid in Escherichia coli BL21 [...] Read more.

l-Methionine γ-lyase (MGL), a pyridoxal 5′-phosphate-dependent enzyme, possesses anti-tumor activity. However, the low activity of MGL blocks the anti-tumor effect. This study describes an efficient production process for the recombinant MGL (rMGL) from Idiomarina constructed using the overexpression plasmid in Escherichia coli BL21 (DE3), purification, and large-scale production. The enzyme produced by the transformants accounted for 53% of the total proteins and accumulated at 1.95 mg/mL using a 500 L fermentor. The enzyme was purified to approximately 99% purity using a high-pressure mechanical homogenizer and nickel (Ni) Sepharose 6 Fast Flow (FF) chromatography. Then, the enzyme was polished by gel filtration, the endotoxins were removed using diethyl-aminoethanol (DEAE) Sepharose FF, and the final product was lyophilized with a vacuum freeze dryer at −35 °C. The specific activity of rMGL in the lyophilized powder was up to 108 U/mg. Compared to the control, the enzyme significantly inhibited cellular proliferation in a concentration-dependent manner as tested using the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay and induced cellular apoptosis as analyzed by Annexin V-fluorescein isothiocyanate (FITC) with fluorescence-activated cell sorting (FACS) in leukemia cells. This paper demonstrated the cloning, overexpression, and large-scale production protocols for rMGL, which enabled rMGL to be used as a novel anti-leukemic drug. Full article

(This article belongs to the Special Issue New Approaches for Activating Silent Biogenetic Gene Clusters in Marine Microorganisms)

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383 KiB

Open AccessReview

Potential Bioactive Compounds from Seaweed for Diabetes Management

by Yusrizam Sharifuddin, Yao-Xian Chin, Phaik-Eem Lim and Siew-Moi Phang

Mar. Drugs 2015, 13(8), 5447-5491; https://doi.org/10.3390/md13085447 - 21 Aug 2015

Cited by 145 | Viewed by 14131

Abstract

Diabetes mellitus is a group of metabolic disorders of the endocrine system characterised by hyperglycaemia. Type II diabetes mellitus (T2DM) constitutes the majority of diabetes cases around the world and are due to unhealthy diet, sedentary lifestyle, as well as rise of obesity [...] Read more.

Diabetes mellitus is a group of metabolic disorders of the endocrine system characterised by hyperglycaemia. Type II diabetes mellitus (T2DM) constitutes the majority of diabetes cases around the world and are due to unhealthy diet, sedentary lifestyle, as well as rise of obesity in the population, which warrants the search for new preventive and treatment strategies. Improved comprehension of T2DM pathophysiology provided various new agents and approaches against T2DM including via nutritional and lifestyle interventions. Seaweeds are rich in dietary fibres, unsaturated fatty acids, and polyphenolic compounds. Many of these seaweed compositions have been reported to be beneficial to human health including in managing diabetes. In this review, we discussed the diversity of seaweed composition and bioactive compounds which are potentially useful in preventing or managing T2DM by targeting various pharmacologically relevant routes including inhibition of enzymes such as α-glucosidase, α-amylase, lipase, aldose reductase, protein tyrosine phosphatase 1B (PTP1B) and dipeptidyl-peptidase-4 (DPP-4). Other mechanisms of action identified, such as anti-inflammatory, induction of hepatic antioxidant enzymes’ activities, stimulation of glucose transport and incretin hormones release, as well as β-cell cytoprotection, were also discussed by taking into consideration numerous in vitro, in vivo, and human studies involving seaweed and seaweed-derived agents. Full article

699 KiB

Open AccessArticle

Hunt for Palytoxins in a Wide Variety of Marine Organisms Harvested in 2010 on the French Mediterranean Coast

by Ronel Biré, Sophie Trotereau, Rodolphe Lemée, Davide Oregioni, Christine Delpont, Sophie Krys and Thierry Guérin

Mar. Drugs 2015, 13(8), 5425-5446; https://doi.org/10.3390/md13085425 - 21 Aug 2015

Cited by 38 | Viewed by 6452

Abstract

During the summer of 2010, 31 species including fish, echinoderms, gastropods, crustaceans, cephalopods and sponges were sampled in the Bay of Villefranche on the French Mediterranean coast and screened for the presence of PLTX-group toxins using the haemolytic assay. Liquid chromatography tandem mass [...] Read more.

During the summer of 2010, 31 species including fish, echinoderms, gastropods, crustaceans, cephalopods and sponges were sampled in the Bay of Villefranche on the French Mediterranean coast and screened for the presence of PLTX-group toxins using the haemolytic assay. Liquid chromatography tandem mass spectrometry (LC-MS/MS) was used for confirmatory purposes and to determine the toxin profile. The mean toxin concentration in the whole flesh of all sampled marine organisms, determined using the lower- (LB) and upper-bound (UB) approach was 4.3 and 5.1 µg·kg⁻¹, respectively, with less than 1% of the results exceeding the European Food Safety Authority (EFSA) threshold of 30 µg·kg⁻¹and the highest values being reported for sea urchins (107.6 and 108.0 µg·kg⁻¹). Toxins accumulated almost exclusively in the digestive tube of the tested species, with the exception of octopus, in which there were detectable toxin amounts in the remaining tissues (RT). The mean toxin concentration in the RT of the sampled organisms (fishes, echinoderms and cephalopods) was 0.7 and 1.7 µg·kg⁻¹ (LB and UB, respectively), with a maximum value of 19.9 µg·kg⁻¹ for octopus RT. The herbivorous and omnivorous organisms were the most contaminated species, indicating that diet influences the contamination process, and the LC-MS/MS revealed that ovatoxin-a was the only toxin detected. Full article

(This article belongs to the Special Issue Marine Neurotoxins)

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Open AccessArticle

The Anti-Inflammatory Effect of Algae-Derived Lipid Extracts on Lipopolysaccharide (LPS)-Stimulated Human THP-1 Macrophages

by Ruairi C. Robertson, Freddy Guihéneuf, Bojlul Bahar, Matthias Schmid, Dagmar B. Stengel, Gerald F. Fitzgerald, R. Paul Ross and Catherine Stanton

Mar. Drugs 2015, 13(8), 5402-5424; https://doi.org/10.3390/md13085402 - 20 Aug 2015

Cited by 135 | Viewed by 14706

Abstract

Algae contain a number of anti-inflammatory bioactive compounds such as omega-3 polyunsaturated fatty acids (n-3 PUFA) and chlorophyll a, hence as dietary ingredients, their extracts may be effective in chronic inflammation-linked metabolic diseases such as cardiovascular disease. In this study, [...] Read more.

Algae contain a number of anti-inflammatory bioactive compounds such as omega-3 polyunsaturated fatty acids (n-3 PUFA) and chlorophyll a, hence as dietary ingredients, their extracts may be effective in chronic inflammation-linked metabolic diseases such as cardiovascular disease. In this study, anti-inflammatory potential of lipid extracts from three red seaweeds (Porphyra dioica, Palmaria palmata and Chondrus crispus) and one microalga (Pavlova lutheri) were assessed in lipopolysaccharide (LPS)-stimulated human THP-1 macrophages. Extracts contained 34%–42% total fatty acids as n-3 PUFA and 5%–7% crude extract as pigments, including chlorophyll a, β-carotene and fucoxanthin. Pretreatment of the THP-1 cells with lipid extract from P. palmata inhibited production of the pro-inflammatory cytokines interleukin (IL)-6 (p < 0.05) and IL-8 (p < 0.05) while that of P. lutheri inhibited IL-6 (p < 0.01) production. Quantitative gene expression analysis of a panel of 92 genes linked to inflammatory signaling pathway revealed down-regulation of the expression of 14 pro-inflammatory genes (TLR1, TLR2, TLR4, TLR8, TRAF5, TRAF6, TNFSF18, IL6R, IL23, CCR1, CCR4, CCL17, STAT3, MAP3K1) by the lipid extracts. The lipid extracts effectively inhibited the LPS-induced pro-inflammatory signaling pathways mediated via toll-like receptors, chemokines and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling molecules. These results suggest that lipid extracts from P. lutheri, P. palmata, P. dioica and C. crispus can inhibit LPS-induced inflammatory pathways in human macrophages. Therefore, algal lipid extracts should be further explored as anti-inflammatory ingredients for chronic inflammation-linked metabolic diseases. Full article

(This article belongs to the Special Issue Marine Lipids)

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Open AccessArticle

Antioxidant, Anti-Nephrolithe Activities and in Vitro Digestibility Studies of Three Different Cyanobacterial Pigment Extracts

by Chetan Paliwal, Tonmoy Ghosh, Khushbu Bhayani, Rahulkumar Maurya and Sandhya Mishra

Mar. Drugs 2015, 13(8), 5384-5401; https://doi.org/10.3390/md13085384 - 20 Aug 2015

Cited by 40 | Viewed by 7651

Abstract

Phycobiliprotein-containing water and carotenoid-containing methanolic extracts of three different cyanobacteria, Pseudanabaena sp., Spirulina sp. and Lyngbya sp., were studied for their DPPH scavenging, iso-bolographic studies, and anti-nephrolithe activities. The best EC₅₀ values for DPPH scavenging were in Lyngbya water (LW, 18.78 ± [...] Read more.

Phycobiliprotein-containing water and carotenoid-containing methanolic extracts of three different cyanobacteria, Pseudanabaena sp., Spirulina sp. and Lyngbya sp., were studied for their DPPH scavenging, iso-bolographic studies, and anti-nephrolithe activities. The best EC₅₀ values for DPPH scavenging were in Lyngbya water (LW, 18.78 ± 1.57 mg·mg⁻¹ DPPH) and Lyngbya methanol (LM, 59.56 ± 37.38 mg·mg⁻¹ DPPH) extracts. Iso-bolographic analysis revealed most of the combinations of extracts were antagonistic to each other, although LM—Spirulina methanol (SM) 1:1 had the highest synergistic rate of 86.65%. In vitro digestion studies showed that DPPH scavenging activity was considerably decreased in all extracts except for Pseudanabaena methanol (PM) and LM after the simulated digestion. All of the extracts were effective in reducing the calcium oxalate crystal size by nearly 60%–65% compared to negative control, while PM and Spirulina water (SW) extracts could inhibit both nucleation and aggregation of calcium oxalate by nearly 60%–80%. Full article

(This article belongs to the Special Issue Marine Functional Food)

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306 KiB

Open AccessReview

Proteins and Carbohydrates from Red Seaweeds: Evidence for Beneficial Effects on Gut Function and Microbiota

by Raúl E. Cian, Silvina R. Drago, Fermín Sánchez De Medina and Olga Martínez-Augustin

Mar. Drugs 2015, 13(8), 5358-5383; https://doi.org/10.3390/md13085358 - 20 Aug 2015

Cited by 166 | Viewed by 12635

Abstract

Based on their composition, marine algae, and namely red seaweeds, are good potential functional foods. Intestinal mucosal barrier function refers to the capacity of the intestine to provide adequate containment of luminal microorganisms and molecules. Here, we will first outline the component of [...] Read more.

Based on their composition, marine algae, and namely red seaweeds, are good potential functional foods. Intestinal mucosal barrier function refers to the capacity of the intestine to provide adequate containment of luminal microorganisms and molecules. Here, we will first outline the component of seaweeds and will summarize the effects of these on the regulation of mucosal barrier function. Special attention will be paid to unique components of red seaweeds: proteins and derived peptides (e.g., phycobiliproteins, glycoproteins that contain “cellulose binding domains”, phycolectins and the related mycosporine-like amino acids) together with polysaccharides (e.g., floridean starch and sulfated galactans, such as carrageenans, agarans and “dl-hybrid”) and minerals. These compounds have been shown to exert prebiotic effects, to regulate intestinal epithelial cell, macrophage and lymphocyte proliferation and differentiation and to modulate the immune response. Molecular mechanisms of action of peptides and polysaccharides are starting to be elucidated, and evidence indicating the involvement of epidermal growth factor receptor (EGFR), insulin-like growth factor receptor (IGFR), Toll-like receptors (TLR) and signal transduction pathways mediated by protein kinase B (PKB or AKT), nuclear factor-κB (NF-κB) and mitogen activated protein kinases (MAPK) will also be summarized. The need for further research is clear, but in vivo experiments point to an overall antiinflammatory effect of these algae, indicating that they can reinforce membrane barrier function. Full article

(This article belongs to the Special Issue Marine Functional Food)

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Open AccessArticle

Effect of an Introduced Phytoene Synthase Gene Expression on Carotenoid Biosynthesis in the Marine Diatom Phaeodactylum tricornutum

by Takashi Kadono, Nozomu Kira, Kengo Suzuki, Osamu Iwata, Takeshi Ohama, Shigeru Okada, Tomohiro Nishimura, Mai Akakabe, Masashi Tsuda and Masao Adachi

Mar. Drugs 2015, 13(8), 5334-5357; https://doi.org/10.3390/md13085334 - 20 Aug 2015

Cited by 62 | Viewed by 9869

Abstract

Carotenoids exert beneficial effects on human health through their excellent antioxidant activity. To increase carotenoid productivity in the marine Pennales Phaeodactylum tricornutum, we genetically engineered the phytoene synthase gene (psy) to improve expression because RNA-sequencing analysis has suggested that the [...] Read more.

Carotenoids exert beneficial effects on human health through their excellent antioxidant activity. To increase carotenoid productivity in the marine Pennales Phaeodactylum tricornutum, we genetically engineered the phytoene synthase gene (psy) to improve expression because RNA-sequencing analysis has suggested that the expression level of psy is lower than other enzyme-encoding genes that are involved in the carotenoid biosynthetic pathway. We isolated psy from P. tricornutum, and this gene was fused with the enhanced green fluorescent protein gene to detect psy expression. After transformation using the microparticle bombardment technique, we obtained several P. tricornutum transformants and confirmed psy expression in their plastids. We investigated the amounts of PSY mRNA and carotenoids, such as fucoxanthin and β-carotene, at different growth phases. The introduction of psy increased the fucoxanthin content of a transformants by approximately 1.45-fold relative to the levels in the wild-type diatom. However, some transformants failed to show a significant increase in the carotenoid content relative to that of the wild-type diatom. We also found that the amount of PSY mRNA at log phase might contribute to the increase in carotenoids in the transformants at stationary phase. Full article

(This article belongs to the Special Issue Metabolites in Diatoms)

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Open AccessReview

Silaffins in Silica Biomineralization and Biomimetic Silica Precipitation

by Carolin C. Lechner and Christian F. W. Becker

Mar. Drugs 2015, 13(8), 5297-5333; https://doi.org/10.3390/md13085297 - 19 Aug 2015

Cited by 102 | Viewed by 12387

Abstract

Biomineralization processes leading to complex solid structures of inorganic material in biological systems are constantly gaining attention in biotechnology and biomedical research. An outstanding example for biomineral morphogenesis is the formation of highly elaborate, nano-patterned silica shells by diatoms. Among the organic macromolecules [...] Read more.

Biomineralization processes leading to complex solid structures of inorganic material in biological systems are constantly gaining attention in biotechnology and biomedical research. An outstanding example for biomineral morphogenesis is the formation of highly elaborate, nano-patterned silica shells by diatoms. Among the organic macromolecules that have been closely linked to the tightly controlled precipitation of silica in diatoms, silaffins play an extraordinary role. These peptides typically occur as complex posttranslationally modified variants and are directly involved in the silica deposition process in diatoms. However, even in vitro silaffin-based peptides alone, with and without posttranslational modifications, can efficiently mediate biomimetic silica precipitation leading to silica material with different properties as well as with encapsulated cargo molecules of a large size range. In this review, the biomineralization process of silica in diatoms is summarized with a specific focus on silaffins and their in vitro silica precipitation properties. Applications in the area of bio- and nanotechnology as well as in diagnostics and therapy are discussed. Full article

(This article belongs to the Special Issue Metabolites in Diatoms)

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Open AccessArticle

The Mucus of Actinia equina (Anthozoa, Cnidaria): An Unexplored Resource for Potential Applicative Purposes

by Loredana Stabili, Roberto Schirosi, Maria Giovanna Parisi, Stefano Piraino and Matteo Cammarata

Mar. Drugs 2015, 13(8), 5276-5296; https://doi.org/10.3390/md13085276 - 19 Aug 2015

Cited by 58 | Viewed by 9564

Abstract

The mucus produced by many marine organisms is a complex mixture of proteins and polysaccharides forming a weak watery gel. It is essential for vital processes including locomotion, navigation, structural support, heterotrophic feeding and defence against a multitude of environmental stresses, predators, parasites, [...] Read more.

The mucus produced by many marine organisms is a complex mixture of proteins and polysaccharides forming a weak watery gel. It is essential for vital processes including locomotion, navigation, structural support, heterotrophic feeding and defence against a multitude of environmental stresses, predators, parasites, and pathogens. In the present study we focused on mucus produced by a benthic cnidarian, the sea anemone Actinia equina (Linnaeus, 1758) for preventing burial by excess sedimentation and for protection. We investigated some of the physico-chemical properties of this matrix such as viscosity, osmolarity, electrical conductivity, protein, carbohydrate, and total lipid contents. Some biological activities such as hemolytic, cytotoxic, and antibacterial lysozyme-like activities were also studied. The A. equina mucus is mainly composed by water (96.2% ± 0.3%), whereas its dry weight is made of 24.2% ± 1.3% proteins and 7.8% ± 0.2% carbohydrates, with the smallest and largest components referable to lipids (0.9%) and inorganic matter (67.1%). The A. equina mucus matrix exhibited hemolytic activity on rabbit erythrocytes, cytotoxic activity against the tumor cell line K562 (human erythromyeloblastoid leukemia) and antibacterial lysozyme-like activity. The findings from this study improve the available information on the mucus composition in invertebrates and have implications for future investigations related to exploitation of A. equina and other sea anemones’ mucus as a source of bioactive compounds of high pharmaceutical and biotechnological interest. Full article

(This article belongs to the Collection Marine Polysaccharides)

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Open AccessReview

Are the Traditional Medical Uses of Muricidae Molluscs Substantiated by Their Pharmacological Properties and Bioactive Compounds?

by Kirsten Benkendorff, David Rudd, Bijayalakshmi Devi Nongmaithem, Lei Liu, Fiona Young, Vicki Edwards, Cathy Avila and Catherine A. Abbott

Mar. Drugs 2015, 13(8), 5237-5275; https://doi.org/10.3390/md13085237 - 18 Aug 2015

Cited by 63 | Viewed by 11760

Abstract

Marine molluscs from the family Muricidae hold great potential for development as a source of therapeutically useful compounds. Traditionally known for the production of the ancient dye Tyrian purple, these molluscs also form the basis of some rare traditional medicines that have been [...] Read more.

Marine molluscs from the family Muricidae hold great potential for development as a source of therapeutically useful compounds. Traditionally known for the production of the ancient dye Tyrian purple, these molluscs also form the basis of some rare traditional medicines that have been used for thousands of years. Whilst these traditional and alternative medicines have not been chemically analysed or tested for efficacy in controlled clinical trials, a significant amount of independent research has documented the biological activity of extracts and compounds from these snails. In particular, Muricidae produce a suite of brominated indoles with anti-inflammatory, anti-cancer and steroidogenic activity, as well as choline esters with muscle-relaxing and pain relieving properties. These compounds could explain some of the traditional uses in wound healing, stomach pain and menstrual problems. However, the principle source of bioactive compounds is from the hypobranchial gland, whilst the shell and operculum are the main source used in most traditional remedies. Thus further research is required to understand this discrepancy and to optimise a quality controlled natural medicine from Muricidae. Full article

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Open AccessArticle

Rare Chromones from a Fungal Mutant of the Marine-Derived Penicillium purpurogenum G59

by Ming-Wen Xia, Cheng-Bin Cui, Chang-Wei Li, Chang-Jing Wu, Ji-Xing Peng and De-Hai Li

Mar. Drugs 2015, 13(8), 5219-5236; https://doi.org/10.3390/md13085219 - 18 Aug 2015

Cited by 33 | Viewed by 5492

Abstract

Three new and rare chromones, named epiremisporine B (2), epiremisporine B1 (3) and isoconiochaetone C (4), along with three known remisporine B (1), coniochaetone A (5) and methyl 8-hydroxy-6-methyl-9-oxo-9H-xanthene-1-carboxylate (6 [...] Read more.

Three new and rare chromones, named epiremisporine B (2), epiremisporine B1 (3) and isoconiochaetone C (4), along with three known remisporine B (1), coniochaetone A (5) and methyl 8-hydroxy-6-methyl-9-oxo-9H-xanthene-1-carboxylate (6) were isolated from a mutant from the diethyl sulfate (DES) mutagenesis of a marine-derived Penicillium purpurogenum G59. The structures of 2–4 including the absolute configurations were determined by spectroscopic methods, especially by NMR analysis and electronic circular dichroism (ECD) experiments in conjunction with calculations. The absolute configuration of the known remisporine B (1) was determined for the first time. Compounds 2 and 3 have a rare feature that has only been reported in one example so far. The compounds 1–6 were evaluated for their cytotoxicity against several human cancer cell lines. The present work explored the great potential of our previous DES mutagenesis strategy for activating silent fungal pathways, which has accelerated the discovery of new bioactive compounds. Full article

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Open AccessArticle

Study on the Antifibrotic Effects of Recombinant Shark Hepatical Stimulator Analogue (r-sHSA) in Vitro and in Vivo

by Ying Wang, Xiaoyuan Zhang, Yang Yang, Xiaohong Yang and Boping Ye

Mar. Drugs 2015, 13(8), 5201-5218; https://doi.org/10.3390/md13085201 - 18 Aug 2015

Cited by 1 | Viewed by 5157

Abstract

Hepatic fibrosis is an effusive wound healing process, characterized by an excessive deposition of extracellular matrix (ECM), as the consequence of chronic liver injury of any etiology. Current therapeutic repertoire for hepatic fibrosis is limited to withdrawal of the noxious agent, which is [...] Read more.

Hepatic fibrosis is an effusive wound healing process, characterized by an excessive deposition of extracellular matrix (ECM), as the consequence of chronic liver injury of any etiology. Current therapeutic repertoire for hepatic fibrosis is limited to withdrawal of the noxious agent, which is not always feasible. Hence, in this article, the antifibrotic effects and possible mechanisms of r-sHSA, a recombinant protein with hepatoprotection potential, were investigated. Using NIH/3T3 (mouse embro-fibroblast cell line), skin fibroblasts (human skin fibroblasts, SFBs) and HSC-T6 (rat hepatic stellate cell line), the in vitro effect of r-sHSA was evaluated by measuring the expression levels of alpha-1 Type I collagen (Col1A1) and α-smooth muscle actin (α-SMA). It turned out those fibrosis indicators were typically inhibited by r-sHSA, suggesting its capacity in HSCs inactivation. The antifibrotic activity of r-sHSA was further investigated in vivo on CCl₄-induced hepatic fibrosis, in view of significant improvement of the biochemical and histological indicators. More specifically, CCl₄-intoxication induced a significant increase in serological biomarkers, e.g., transaminase (AST, ALT), and alkaline phosphatase (ALP), as well as disturbed hepatic antioxidative status; most of the parameters were spontaneously ameliorated to a large extent by withdrawal of CCl₄, although the fibrotic lesion was observed histologically. In contrast, r-sHSA treatment markedly eliminated fibrous deposits and restored architecture of the liver in a dose dependent manner, concomitantly with the phenomena of inflammation relief and HSCs deactivation. To sum up, these findings suggest a therapeutic potential for r-sHSA in hepatic fibrosis, though further studies are required. Full article

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Open AccessArticle

Hormaomycins B and C: New Antibiotic Cyclic Depsipeptides from a Marine Mudflat-Derived Streptomyces sp.

by Munhyung Bae, Beomkoo Chung, Ki-Bong Oh, Jongheon Shin and Dong-Chan Oh

Mar. Drugs 2015, 13(8), 5187-5200; https://doi.org/10.3390/md13085187 - 14 Aug 2015

Cited by 46 | Viewed by 7545

Abstract

Alterations in microbial culture conditions may trigger the production of diverse bioactive secondary metabolites. While applying various culture conditions and monitoring secondary metabolite profiles using LC/MS, hormaomycins B and C (1 and 2) were discovered from a marine mudflat-derived actinomycete, Streptomyces [...] Read more.

Alterations in microbial culture conditions may trigger the production of diverse bioactive secondary metabolites. While applying various culture conditions and monitoring secondary metabolite profiles using LC/MS, hormaomycins B and C (1 and 2) were discovered from a marine mudflat-derived actinomycete, Streptomyces sp., collected in Mohang, Korea. The planar structures of the hormaomycins, which bear structurally-unique units, such as 4-(Z)-propenylproline, 3-(2-nitrocyclopropyl)alanine, 5-chloro-1-hydroxypyrrol-2-carboxylic acid and b-methylphenylalanine, were established as the first natural analogues belonging to the hormaomycin peptide class. The absolute configurations of 1 and 2 were deduced by comparing their CD spectra with that of hormaomycin. These hormaomycins exhibited significant inhibitory effects against various pathogenic Gram-positive and Gram-negative bacteria. Full article

(This article belongs to the Special Issue Marine Secondary Metabolites)

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Open AccessReview

Chitosan: An Update on Potential Biomedical and Pharmaceutical Applications

by Randy Chi Fai Cheung, Tzi Bun Ng, Jack Ho Wong and Wai Yee Chan

Mar. Drugs 2015, 13(8), 5156-5186; https://doi.org/10.3390/md13085156 - 14 Aug 2015

Cited by 1000 | Viewed by 33056

Abstract

Chitosan is a natural polycationic linear polysaccharide derived from chitin. The low solubility of chitosan in neutral and alkaline solution limits its application. Nevertheless, chemical modification into composites or hydrogels brings to it new functional properties for different applications. Chitosans are recognized as [...] Read more.

Chitosan is a natural polycationic linear polysaccharide derived from chitin. The low solubility of chitosan in neutral and alkaline solution limits its application. Nevertheless, chemical modification into composites or hydrogels brings to it new functional properties for different applications. Chitosans are recognized as versatile biomaterials because of their non-toxicity, low allergenicity, biocompatibility and biodegradability. This review presents the recent research, trends and prospects in chitosan. Some special pharmaceutical and biomedical applications are also highlighted. Full article

(This article belongs to the Collection Marine Polysaccharides)

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Open AccessReview

Carotenoids from Marine Microalgae: A Valuable Natural Source for the Prevention of Chronic Diseases

by Maria Filomena de Jesus Raposo, Alcina Maria Miranda Bernardo De Morais and Rui Manuel Santos Costa De Morais

Mar. Drugs 2015, 13(8), 5128-5155; https://doi.org/10.3390/md13085128 - 14 Aug 2015

Cited by 165 | Viewed by 11699

Abstract

Epidemiological studies have shown a relation between antioxidants and the prevention of several chronic diseases. Microalgae are a potential novel source of bioactive molecules, including a wide range of different carotenoids that can be used as nutraceuticals, food supplements and novel food products. [...] Read more.

Epidemiological studies have shown a relation between antioxidants and the prevention of several chronic diseases. Microalgae are a potential novel source of bioactive molecules, including a wide range of different carotenoids that can be used as nutraceuticals, food supplements and novel food products. The objective of this review is (i) to update the research that has been carried out on the most known carotenoids produced by marine microalgae, including reporting on their high potentialities to produce other less known important compounds; (ii) to compile the work that has been done in order to establish some relationship between carotenoids and oxidative protection and treatment; (iii) to summarize the association of oxidative stress and the various reactive species including free radicals with several human diseases; and (iv) to provide evidence of the potential of carotenoids from marine microalgae to be used as therapeutics to treat or prevent these oxidative stress-related diseases. Full article

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Open AccessArticle

Comparison of Cell Disruption Methods for Improving Lipid Extraction from Thraustochytrid Strains

by Avinesh R. Byreddy, Adarsha Gupta, Colin J. Barrow and Munish Puri

Mar. Drugs 2015, 13(8), 5111-5127; https://doi.org/10.3390/md13085111 - 11 Aug 2015

Cited by 144 | Viewed by 12047

Abstract

Lipid extraction is an integral part of biodiesel production, as it facilitates the release of fatty acids from algal cells. To utilise thraustochytrids as a potential source for lipid production. We evaluated the extraction efficiency of various solvents and solvent combinations for lipid [...] Read more.

Lipid extraction is an integral part of biodiesel production, as it facilitates the release of fatty acids from algal cells. To utilise thraustochytrids as a potential source for lipid production. We evaluated the extraction efficiency of various solvents and solvent combinations for lipid extraction from Schizochytrium sp. S31 and Thraustochytrium sp. AMCQS5-5. The maximum lipid extraction yield was 22% using a chloroform:methanol ratio of 2:1. We compared various cell disruption methods to improve lipid extraction yields, including grinding with liquid nitrogen, bead vortexing, osmotic shock, water bath, sonication and shake mill. The highest lipid extraction yields were obtained using osmotic shock and 48.7% from Schizochytrium sp. S31 and 29.1% from Thraustochytrium sp. AMCQS5-5. Saturated and monounsaturated fatty acid contents were more than 60% in Schizochytrium sp. S31 which suggests their suitability for biodiesel production. Full article

(This article belongs to the Special Issue Marine Lipids)

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Open AccessArticle

Structure-Activity Relationships of the Bioactive Thiazinoquinone Marine Natural Products Thiaplidiaquinones A and B

by Jacquie L. Harper, Iman M. Khalil, Lisa Shaw, Marie-Lise Bourguet-Kondracki, Joëlle Dubois, Alexis Valentin, David Barker and Brent R. Copp

Mar. Drugs 2015, 13(8), 5102-5110; https://doi.org/10.3390/md13085102 - 10 Aug 2015

Cited by 15 | Viewed by 6299

Abstract

In an effort to more accurately define the mechanism of cell death and to establish structure-activity relationship requirements for the marine meroterpenoid alkaloids thiaplidiaquinones A and B, we have evaluated not only the natural products but also dioxothiazine regioisomers and two precursor quinones [...] Read more.

In an effort to more accurately define the mechanism of cell death and to establish structure-activity relationship requirements for the marine meroterpenoid alkaloids thiaplidiaquinones A and B, we have evaluated not only the natural products but also dioxothiazine regioisomers and two precursor quinones in a range of bioassays. While the natural products were found to be weak inducers of ROS in Jurkat cells, the dioxothiazine regioisomer of thiaplidiaquinone A and a synthetic precursor to thiaplidiaquinone B were found to be moderately potent inducers. Intriguingly, and in contrast to previous reports, the mechanism of Jurkat cell death (necrosis vs. apoptosis) was found to be dependent upon the positioning of one of the geranyl sidechains in the compounds with thiaplidiaquinone A and its dioxothiazine regioisomer causing death dominantly by necrosis, while thiaplidiaquinone B and its dioxothiazine isomer caused cell death via apoptosis. The dioxothiazine regioisomer of thiaplidiaquinone A exhibited more potent in vitro antiproliferative activity against human tumor cells, with NCI sub-panel selectivity towards melanoma cell lines. The non-natural dioxothiazine regioisomers were also more active in antiplasmodial and anti-farnesyltransferase assays than their natural product counterparts. The results highlight the important role that natural product total synthesis can play in not only helping understand the structural basis of biological activity of natural products, but also the discovery of new bioactive scaffolds. Full article

(This article belongs to the Special Issue Marine Bioactive Natural Product Studies—A Southern Hemisphere Perspective)

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Porifera Lectins: Diversity, Physiological Roles and Biotechnological Potential

by Johan Gardères, Marie-Lise Bourguet-Kondracki, Bojan Hamer, Renato Batel, Heinz C. Schröder and Werner E. G. Müller

Mar. Drugs 2015, 13(8), 5059-5101; https://doi.org/10.3390/md13085059 - 7 Aug 2015

Cited by 33 | Viewed by 9143

Abstract

An overview on the diversity of 39 lectins from the phylum Porifera is presented, including 38 lectins, which were identified from the class of demosponges, and one lectin from the class of hexactinellida. Their purification from crude extracts was mainly performed by using [...] Read more.

An overview on the diversity of 39 lectins from the phylum Porifera is presented, including 38 lectins, which were identified from the class of demosponges, and one lectin from the class of hexactinellida. Their purification from crude extracts was mainly performed by using affinity chromatography and gel filtration techniques. Other protocols were also developed in order to collect and study sponge lectins, including screening of sponge genomes and expression in heterologous bacterial systems. The characterization of the lectins was performed by Edman degradation or mass spectrometry. Regarding their physiological roles, sponge lectins showed to be involved in morphogenesis and cell interaction, biomineralization and spiculogenesis, as well as host defense mechanisms and potentially in the association between the sponge and its microorganisms. In addition, these lectins exhibited a broad range of bioactivities, including modulation of inflammatory response, antimicrobial and cytotoxic activities, as well as anticancer and neuromodulatory activity. In view of their potential pharmacological applications, sponge lectins constitute promising molecules of biotechnological interest. Full article

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Open AccessReview

Eribulin in Cancer Treatment

by Umang Swami, Umang Shah and Sanjay Goel

Mar. Drugs 2015, 13(8), 5016-5058; https://doi.org/10.3390/md13085016 - 7 Aug 2015

Cited by 57 | Viewed by 11648

Abstract

Halichondrin B is a complex, natural, polyether macrolide derived from marine sponges. Eribulin is a structurally-simplified, synthetic, macrocyclic ketone analogue of Halichondrin B. Eribulin was approved by United States Food and Drug Administration in 2010 as a third-line therapy for metastatic breast cancer [...] Read more.

Halichondrin B is a complex, natural, polyether macrolide derived from marine sponges. Eribulin is a structurally-simplified, synthetic, macrocyclic ketone analogue of Halichondrin B. Eribulin was approved by United States Food and Drug Administration in 2010 as a third-line therapy for metastatic breast cancer patients who have previously been treated with an anthracycline and a taxane. It has a unique microtubule dynamics inhibitory action. Phase III studies have either been completed or are currently ongoing in breast cancer, soft tissue sarcoma, and non-small cell lung cancer. Phase I and II studies in multiple cancers and various combinations are currently ongoing. This article reviews the available information on eribulin with respect to its clinical pharmacology, pharmacokinetics, pharmacodynamics, mechanism of action, metabolism, preclinical studies, and with special focus on clinical trials. Full article

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Open AccessArticle

Metabolomic Analysis of Blood Plasma after Oral Administration of N-acetyl-d-Glucosamine in Dogs

by Tomohiro Osaki, Seiji Kurozumi, Kimihiko Sato, Taro Terashi, Kazuo Azuma, Yusuke Murahata, Takeshi Tsuka, Norihiko Ito, Tomohiro Imagawa, Saburo Minami and Yoshiharu Okamoto

Mar. Drugs 2015, 13(8), 5007-5015; https://doi.org/10.3390/md13085007 - 7 Aug 2015

Cited by 2 | Viewed by 6035

Abstract

N-acetyl-d-glucosamine (GlcNAc) is a monosaccharide that polymerizes linearly through (1,4)-β-linkages. GlcNAc is the monomeric unit of the polymer chitin. GlcNAc is a basic component of hyaluronic acid and keratin sulfate found on the cell surface. The aim of this study was to [...] Read more.

N-acetyl-d-glucosamine (GlcNAc) is a monosaccharide that polymerizes linearly through (1,4)-β-linkages. GlcNAc is the monomeric unit of the polymer chitin. GlcNAc is a basic component of hyaluronic acid and keratin sulfate found on the cell surface. The aim of this study was to examine amino acid metabolism after oral GlcNAc administration in dogs. Results showed that plasma levels of ectoine were significantly higher after oral administration of GlcNAc than prior to administration (p < 0.001). To our knowledge, there have been no reports of increased ectoine concentrations in the plasma. The mechanism by which GlcNAc administration leads to increased ectoine plasma concentration remains unclear; future studies are required to clarify this mechanism. Full article

(This article belongs to the Special Issue Marine Functional Food)

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Open AccessArticle

Lipopolysaccharides from Commensal and Opportunistic Bacteria: Characterization and Response of the Immune System of the Host Sponge Suberites domuncula

by Johan Gardères, Gilles Bedoux, Vasiliki Koutsouveli, Sterenn Crequer, Florie Desriac and Gaël Le Pennec

Mar. Drugs 2015, 13(8), 4985-5006; https://doi.org/10.3390/md13084985 - 7 Aug 2015

Cited by 18 | Viewed by 6431

Abstract

Marine sponges harbor a rich bacterioflora with which they maintain close relationships. However, the way these animals make the distinction between bacteria which are consumed to meet their metabolic needs and opportunistic and commensal bacteria which are hosted is not elucidated. Among the [...] Read more.

Marine sponges harbor a rich bacterioflora with which they maintain close relationships. However, the way these animals make the distinction between bacteria which are consumed to meet their metabolic needs and opportunistic and commensal bacteria which are hosted is not elucidated. Among the elements participating in this discrimination, bacterial cell wall components such as lipopolysaccharides (LPS) could play a role. In the present study, we investigated the LPS chemical structure of two bacteria associated with the sponge Suberites domuncula: a commensal Endozoicomonas sp. and an opportunistic Pseudoalteromonas sp. Electrophoretic patterns indicated different LPS structures for these bacteria. The immunomodulatory lipid A was isolated after mild acetic acid hydrolysis. The electrospray ionization ion-trap mass spectra revealed monophosphorylated molecules corresponding to tetra- and pentaacylated structures with common structural features between the two strains. Despite peculiar structural characteristics, none of these two LPS influenced the expression of the macrophage-expressed gene S. domuncula unlike the Escherichia coli ones. Further research will have to include a larger number of genes to understand how this animal can distinguish between LPS with resembling structures and discriminate between bacteria associated with it. Full article

(This article belongs to the Special Issue Marine Lipopolysaccharides)

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Signal Transducers and Activators of Transcription (STAT) Regulatory Networks in Marine Organisms: From Physiological Observations towards Marine Drug Discovery

by Jin-Young Lee, Barbora Orlikova and Marc Diederich

Mar. Drugs 2015, 13(8), 4967-4984; https://doi.org/10.3390/md13084967 - 7 Aug 2015

Cited by 18 | Viewed by 9367

Abstract

Part of our ocean’s richness comes from its extensive history of supporting life, resulting in a highly diverse ecological system. To date, over 250,000 species of marine organisms have been identified, but it is speculated that the actual number of marine species exceeds [...] Read more.

Part of our ocean’s richness comes from its extensive history of supporting life, resulting in a highly diverse ecological system. To date, over 250,000 species of marine organisms have been identified, but it is speculated that the actual number of marine species exceeds one million, including several hundreds of millions of species of marine microorganisms. Past studies suggest that approximately 70% of all deep-sea microorganisms, gorgonians, and sea sponges produce secondary metabolites with anti-cancer activities. Recently, novel FDA-approved drugs derived from marine sponges have been shown to reduce metastatic breast cancer, malignant lymphoma, and Hodgkin’s disease. Despite the fact that many marine natural products have been shown to possess a good inhibition potential against most of the cancer-related cell signaling pathways, only a few marine natural products have been shown to target JAK/STAT signaling. In the present paper, we describe the JAK/STAT signaling pathways found in marine organisms, before elaborating on the recent advances in the field of STAT inhibition by marine natural products and the potential application in anti-cancer drug discovery. Full article

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Open AccessArticle

Epipolythiodiketopiperazines from the Marine Derived Fungus Dichotomomyces cejpii with NF-κB Inhibitory Potential

by Henrik Harms, Barbora Orlikova, Seungwon Ji, Damun Nesaei-Mosaferan, Gabriele M. König and Marc Diederich

Mar. Drugs 2015, 13(8), 4949-4966; https://doi.org/10.3390/md13084949 - 6 Aug 2015

Cited by 21 | Viewed by 7110

Abstract

The Ascomycota Dichotomomyces cejpii was isolated from the marine sponge Callyspongia cf. C. flammea. A new gliotoxin derivative, 6-acetylmonodethiogliotoxin (1) was obtained from fungal extracts. Compounds 2 and 3, methylthio-gliotoxin derivatives were formerly only known as semi-synthetic compounds and are [...] Read more.

The Ascomycota Dichotomomyces cejpii was isolated from the marine sponge Callyspongia cf. C. flammea. A new gliotoxin derivative, 6-acetylmonodethiogliotoxin (1) was obtained from fungal extracts. Compounds 2 and 3, methylthio-gliotoxin derivatives were formerly only known as semi-synthetic compounds and are here described as natural products. Additionally the polyketide heveadride (4) was isolated. Compounds 1, 2 and 4 dose-dependently down-regulated TNFα-induced NF-κB activity in human chronic myeloid leukemia cells with IC_50s of 38.5 ± 1.2 µM, 65.7 ± 2.0 µM and 82.7 ± 11.3 µM, respectively. The molecular mechanism was studied with the most potent compound 1 and results indicate downstream inhibitory effects targeting binding of NF-κB to DNA. Compound 1 thus demonstrates potential of epimonothiodiketopiperazine-derived compounds for the development of NF-κB inhibitors. Full article

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Open AccessArticle

The Marine-Derived Fungus Clonostachys rosea, Source of a Rare Conjugated 4-Me-6E,8E-hexadecadienoic Acid Reducing Viability of MCF-7 Breast Cancer Cells and Gene Expression of Lipogenic Enzymes

by Ana Camila Dos Santos Dias, Nicolas Ruiz, Aurélie Couzinet-Mossion, Samuel Bertrand, Muriel Duflos, Yves-François Pouchus, Gilles Barnathan, Hassan Nazih and Gaetane Wielgosz-Collin

Mar. Drugs 2015, 13(8), 4934-4948; https://doi.org/10.3390/md13084934 - 6 Aug 2015

Cited by 21 | Viewed by 6254

Abstract

A marine-derived strain of Clonostachys rosea isolated from sediments of the river Loire estuary (France) was investigated for its high lipid production. The fungal strain was grown on six different culture media to explore lipid production changes. An original branched conjugated fatty acid, [...] Read more.

A marine-derived strain of Clonostachys rosea isolated from sediments of the river Loire estuary (France) was investigated for its high lipid production. The fungal strain was grown on six different culture media to explore lipid production changes. An original branched conjugated fatty acid, mainly present in triglycerides and mostly produced when grown on DCA (23% of total fatty acid composition). It was identified as 4-Me-6E,8E-hexadecadienoic on the basis of spectroscopic analyses. This fatty acid reduced viability of MCF-7 breast cancer cells in a dose dependent manner (up to 63%) at physiological free fatty acid human plasma concentration (100 μM). Reduction of gene expression of two lipogenic enzymes, the acetyl CoA carboxylase (ACC) and the fatty acid synthase (FAS) was evaluated to explore the mechanisms of action of 4-Me-6E,8E-16:2 acid. At 50 μM, 50% and 35% of mRNA gene expression inhibition were observed for ACC and FAS, respectively. Full article

(This article belongs to the Special Issue Marine Lipids)

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Chemistry of Renieramycins. Part 14: Total Synthesis of Renieramycin I and Practical Synthesis of Cribrostatin 4 (Renieramycin H)

by Masashi Yokoya, Keiichiro Kobayashi, Mitsuhiro Sato and Naoki Saito

Mar. Drugs 2015, 13(8), 4915-4933; https://doi.org/10.3390/md13084915 - 6 Aug 2015

Cited by 13 | Viewed by 7382

Abstract

The first total synthesis of (±)-renieramycin I, which was isolated from the Indian bright blue sponge Haliclona cribricutis, is described. The key step is the selenium oxide oxidation of pentacyclic bis-p-quinone derivative (3) stereo- and regioselectively. We also [...] Read more.

The first total synthesis of (±)-renieramycin I, which was isolated from the Indian bright blue sponge Haliclona cribricutis, is described. The key step is the selenium oxide oxidation of pentacyclic bis-p-quinone derivative (3) stereo- and regioselectively. We also report a large-scale synthesis of cribrostatin 4 (renieramycin H) via the C3-C4 double bond formation in an early stage based on the Avendaño’s protocol, from readily available 1-acetyl-3-(3-methyl-2,4,5-trimethylphenyl)methyl-piperazine-2,5-dione (8) in 18 steps (8.3% overall yield). The synthesis provides unambiguous evidence supporting the original structure of renieramycin I. Full article

(This article belongs to the Special Issue Marine Secondary Metabolites)

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Open AccessReview

Marine Indole Alkaloids

by Natalie Netz and Till Opatz

Mar. Drugs 2015, 13(8), 4814-4914; https://doi.org/10.3390/md13084814 - 6 Aug 2015

Cited by 181 | Viewed by 18996

Abstract

Marine indole alkaloids comprise a large and steadily growing group of secondary metabolites. Their diverse biological activities make many compounds of this class attractive starting points for pharmaceutical development. Several marine-derived indoles were found to possess cytotoxic, antineoplastic, antibacterial and antimicrobial activities, in [...] Read more.

Marine indole alkaloids comprise a large and steadily growing group of secondary metabolites. Their diverse biological activities make many compounds of this class attractive starting points for pharmaceutical development. Several marine-derived indoles were found to possess cytotoxic, antineoplastic, antibacterial and antimicrobial activities, in addition to the action on human enzymes and receptors. The newly isolated indole alkaloids of marine origin since the last comprehensive review in 2003 are reported, and biological aspects will be discussed. Full article

(This article belongs to the Special Issue Marine Secondary Metabolites)

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Fucoxanthinol, Metabolite of Fucoxanthin, Improves Obesity-Induced Inflammation in Adipocyte Cells

by Hayato Maeda, Shogo Kanno, Mei Kodate, Masashi Hosokawa and Kazuo Miyashita

Mar. Drugs 2015, 13(8), 4799-4813; https://doi.org/10.3390/md13084799 - 4 Aug 2015

Cited by 69 | Viewed by 9029

Abstract

Fucoxanthin (Fx) is a marine carotenoid found in edible brown seaweeds. We previously reported that dietary Fx metabolite into fucoxanthinol (FxOH), attenuates the weight gain of white adipose tissue of diabetic/obese KK-A^y mice. In this study, to evaluate anti-diabetic effects of [...] Read more.

Fucoxanthin (Fx) is a marine carotenoid found in edible brown seaweeds. We previously reported that dietary Fx metabolite into fucoxanthinol (FxOH), attenuates the weight gain of white adipose tissue of diabetic/obese KK-A^y mice. In this study, to evaluate anti-diabetic effects of Fx, we investigated improving the effect of insulin resistance on the diabetic model of KK-A^y mice. Furthermore, preventing the effect of FxOH on low-grade chronic inflammation related to oxidative stress was evaluated on 3T3-L1 adipocyte cells and a RAW264.7 macrophage cell co-culture system. A diet containing 0.1% Fx was fed to diabetic model KK-A^y mice for three weeks, then glucose tolerance was observed. Fx diet significantly improved glucose tolerance compared with the control diet group. In in vitro studies, FxOH showed suppressed tumor necrosis factor-α (TNF-α), and monocyte chemotactic protein-1 (MCP-1) mRNA expression and protein levels in a co-culture of adipocyte and macrophage cells. These findings suggest that Fx ameliorates glucose tolerance in the diabetic model mice. Furthermore, FxOH, a metabolite of Fx, suppresses low-grade chronic inflammation in adipocyte cells. Full article

(This article belongs to the Special Issue Marine Carotenoids and Oxidative Stress)

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Fucoxanthin and Its Metabolite Fucoxanthinol in Cancer Prevention and Treatment

by Luc J. Martin

Mar. Drugs 2015, 13(8), 4784-4798; https://doi.org/10.3390/md13084784 - 31 Jul 2015

Cited by 102 | Viewed by 10838

Abstract

Fucoxanthin is a carotenoid present in the chloroplasts of brown seaweeds. When ingested, it is metabolized mainly to fucoxanthinol by digestive enzymes of the gastrointestinal tract. These compounds have been shown to have many beneficial health effects, including anti-mutagenic, anti-diabetic, anti-obesity, anti-inflammatory and [...] Read more.

Fucoxanthin is a carotenoid present in the chloroplasts of brown seaweeds. When ingested, it is metabolized mainly to fucoxanthinol by digestive enzymes of the gastrointestinal tract. These compounds have been shown to have many beneficial health effects, including anti-mutagenic, anti-diabetic, anti-obesity, anti-inflammatory and anti-neoplastic actions. In every cancer tested, modulatory actions of fucoxanthinol on viability, cell-cycle arrest, apoptosis and members of the NF-κB pathway were more pronounced than that of fucoxanthin. Anti-proliferative and cancer preventing influences of fucoxanthin and fucoxanthinol are mediated through different signalling pathways, including the caspases, Bcl-2 proteins, MAPK, PI3K/Akt, JAK/STAT, AP-1, GADD45, and several other molecules that are involved in cell cycle arrest, apoptosis, anti-angiogenesis or inhibition of metastasis. In this review, we address the mechanisms of action of fucoxanthin and fucoxanthinol according to different types of cancers. Current findings suggest that these compounds could be effective for treatment and/or prevention of cancer development and aggressiveness. Full article

(This article belongs to the Special Issue Marine Carotenoids and Oxidative Stress)

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Open AccessReview

The Sound of Silence: Activating Silent Biosynthetic Gene Clusters in Marine Microorganisms

by F. Jerry Reen, Stefano Romano, Alan D. W. Dobson and Fergal O'Gara

Mar. Drugs 2015, 13(8), 4754-4783; https://doi.org/10.3390/md13084754 - 31 Jul 2015

Cited by 130 | Viewed by 14577

Abstract

Unlocking the rich harvest of marine microbial ecosystems has the potential to both safeguard the existence of our species for the future, while also presenting significant lifestyle benefits for commercial gain. However, while significant advances have been made in the field of marine [...] Read more.

Unlocking the rich harvest of marine microbial ecosystems has the potential to both safeguard the existence of our species for the future, while also presenting significant lifestyle benefits for commercial gain. However, while significant advances have been made in the field of marine biodiscovery, leading to the introduction of new classes of therapeutics for clinical medicine, cosmetics and industrial products, much of what this natural ecosystem has to offer is locked in, and essentially hidden from our screening methods. Releasing this silent potential represents a significant technological challenge, the key to which is a comprehensive understanding of what controls these systems. Heterologous expression systems have been successful in awakening a number of these cryptic marine biosynthetic gene clusters (BGCs). However, this approach is limited by the typically large size of the encoding sequences. More recently, focus has shifted to the regulatory proteins associated with each BGC, many of which are signal responsive raising the possibility of exogenous activation. Abundant among these are the LysR-type family of transcriptional regulators, which are known to control production of microbial aromatic systems. Although the environmental signals that activate these regulatory systems remain unknown, it offers the exciting possibility of evoking mimic molecules and synthetic expression systems to drive production of potentially novel natural products in microorganisms. Success in this field has the potential to provide a quantum leap forward in medical and industrial bio-product development. To achieve these new endpoints, it is clear that the integrated efforts of bioinformaticians and natural product chemists will be required as we strive to uncover new and potentially unique structures from silent or cryptic marine gene clusters. Full article

(This article belongs to the Special Issue New Approaches for Activating Silent Biogenetic Gene Clusters in Marine Microorganisms)

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Antitumor Effects and Related Mechanisms of Penicitrinine A, a Novel Alkaloid with a Unique Spiro Skeleton from the Marine Fungus Penicillium citrinum

by Qin-Ying Liu, Tong Zhou, Yang-Yang Zhao, Li Chen, Mei-Wei Gong, Qi-Wen Xia, Min-Gang Ying, Qiu-Hong Zheng and Qi-Qing Zhang

Mar. Drugs 2015, 13(8), 4733-4753; https://doi.org/10.3390/md13084733 - 31 Jul 2015

Cited by 52 | Viewed by 7025

Abstract

Penicitrinine A, a novel alkaloid with a unique spiro skeleton, was isolated from a marine-derived fungus Penicillium citrinum. In this study, the isolation, structure and biosynthetic pathway elucidation of the new compound were described. This new compound showed anti-proliferative activity on multiple [...] Read more.

Penicitrinine A, a novel alkaloid with a unique spiro skeleton, was isolated from a marine-derived fungus Penicillium citrinum. In this study, the isolation, structure and biosynthetic pathway elucidation of the new compound were described. This new compound showed anti-proliferative activity on multiple tumor types. Among them, the human malignant melanoma cell A-375 was confirmed to be the most sensitive. Morphologic evaluation, apoptosis rate analysis, Western blot and real-time quantitative PCR (RT-qPCR) results showed penicitrinine A could significantly induce A-375 cell apoptosis by decreasing the expression of Bcl-2 and increasing the expression of Bax. Moreover, we investigated the anti-metastatic effects of penicitrinine A in A-375 cells by wound healing assay, trans-well assay, Western blot and RT-qPCR. The results showed penicitrinine A significantly suppressed metastatic activity of A-375 cells by regulating the expression of MMP-9 and its specific inhibitor TIMP-1. These findings suggested that penicitrinine A might serve as a potential antitumor agent, which could inhibit the proliferation and metastasis of tumor cells. Full article

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Mar. Drugs, Volume 13, Issue 8 (August 2015) – 38 articles , Pages 4576-5507

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