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Marine Drugs
Volume 12
Issue 1
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Mar. Drugs, Volume 12, Issue 1 (January 2014) – 30 articles , Pages 1-567

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Article
Apoptogenic Metabolites in Fractions of the Benthic Diatom Cocconeis scutellum parva
by Valerio Zupo, Friedrich Jüttner, Chingoileima Maibam, Emanuela Butera and Judith F. Blom
Mar. Drugs 2014, 12(1), 547-567; https://doi.org/10.3390/md12010547 - 22 Jan 2014
Cited by 19 | Viewed by 7849
Abstract
Benthic diatoms of the genus Cocconeis contain a specific apoptogenic activity. It triggers a fast destruction of the androgenic gland in the early post-larval life of the marine shrimp Hippolyte inermis, leading to the generation of small females. Previous in vitro investigations [...] Read more.
Benthic diatoms of the genus Cocconeis contain a specific apoptogenic activity. It triggers a fast destruction of the androgenic gland in the early post-larval life of the marine shrimp Hippolyte inermis, leading to the generation of small females. Previous in vitro investigations demonstrated that crude extracts of these diatoms specifically activate a dose-dependent apoptotic process in human cancer cells (BT20 breast carcinoma) but not in human normal lymphocytes. Here, a bioassay-guided fractionation has been performed to detect the apoptogenic compound(s). Various HPLC separation systems were needed to isolate the active fractions, since the apoptogenic metabolite is highly active, present in low amounts and is masked by abundant but non-active cellular compounds. The activity is due to at least two compounds characterized by different polarities, a hydrophilic and a lipophilic fraction. We purified the lipophilic fraction, which led to the characterization of an active sub-fraction containing a highly lipophilic compound, whose molecular structure has not yet been identified, but is under investigation. The results point to the possible medical uses of the active compound. Once the molecular structure has been identified, the study and modulation of apoptotic processes in various types of cells will be possible. Full article
(This article belongs to the Special Issue Metabolites in Diatoms)
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Review
Marine Natural Products with P-Glycoprotein Inhibitor Properties
by Dioxelis Lopez and Sergio Martinez-Luis
Mar. Drugs 2014, 12(1), 525-546; https://doi.org/10.3390/md12010525 - 22 Jan 2014
Cited by 67 | Viewed by 10626
Abstract
P-glycoprotein (P-gp) is a protein belonging to the ATP-binding cassette (ABC) transporters superfamily that has clinical relevance due to its role in drug metabolism and multi-drug resistance (MDR) in several human pathogens and diseases. P-gp is a major cause of drug resistance in [...] Read more.
P-glycoprotein (P-gp) is a protein belonging to the ATP-binding cassette (ABC) transporters superfamily that has clinical relevance due to its role in drug metabolism and multi-drug resistance (MDR) in several human pathogens and diseases. P-gp is a major cause of drug resistance in cancer, parasitic diseases, epilepsy and other disorders. This review article aims to summarize the research findings on the marine natural products with P-glycoprotein inhibitor properties. Natural compounds that modulate P-gp offer great possibilities for semi-synthetic modification to create new drugs and are valuable research tools to understand the function of complex ABC transporters. Full article
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Article
Analysis of the Toxicity and Histopathology Induced by the Oral Administration of Pseudanabaena galeata and Geitlerinema splendidum (Cyanobacteria) Extracts to Mice
by Marisa Rangel, Joyce C. G. Martins, Angélica Nunes Garcia, Geanne A. A. Conserva, Adriana Costa-Neves, Célia Leite Sant'Anna and Luciana Retz De Carvalho
Mar. Drugs 2014, 12(1), 508-524; https://doi.org/10.3390/md12010508 - 22 Jan 2014
Cited by 21 | Viewed by 10547
Abstract
Cyanobacteria are common members of the freshwater microbiota in lakes and drinking water reservoirs, and are responsible for several cases of human intoxications in Brazil. Pseudanabaena galeata and Geitlerinema splendidum are examples of the toxic species that are very frequently found in reservoirs [...] Read more.
Cyanobacteria are common members of the freshwater microbiota in lakes and drinking water reservoirs, and are responsible for several cases of human intoxications in Brazil. Pseudanabaena galeata and Geitlerinema splendidum are examples of the toxic species that are very frequently found in reservoirs in Sao Paulo, which is the most densely populated area in Brazil. In the search for toxic strains collected from water reservoirs and maintained in the Cyanobacterial Culture Collection (CCIBt) of the Institute of Botany of Brazil, the acetic acid extracts (AE) of P. galeata CCIBt 3082 and G. splendidum CCIBt 3223 were analyzed by planar chromatography, which indicated the absence of cyanotoxins. Animal tests were then carried out, and both extracts were found to induce toxic effects in mice when administered intraperitoneally. The present study aimed to investigate whether the oral ingestion of the above mentioned cyanobacteria extracts would also induce toxic effects in mice. Necropsy and histopathological studies were conducted using tissue samples from the animals, which were euthanized one week after the administration of the extracts. The AE of P. galeata did not cause death but did induce transient symptoms, including eyebrow ptosis, straub tail, and pain. The euthanized animals presented hemorrhage in the liver, whereas the histological analysis showed disorganization of the hepatic parenchyma, necrosis, hyperemia, and proximity of the centrilobular vein in the liver. In addition, alterations in the convoluted tubules of the kidneys were observed, and the lungs were unaffected. The AE of G. splendidum caused only one death, and induced transient symptoms, such as dyspnea, paralysis, and pain, in the other mice. The necropsy of the euthanized mice showed hemorrhage in the lungs and liver. The lungs presented hemorrhagic focuses, alveolar collapse, and granulomatous foci. The liver presented hemorrhagic and enlarged sinusoids, hyperemia, proximity of the centrilobular vein, and disorganization of the hepatic parenchyma. Some areas also exhibited an inflammatory infiltrate and calcified tissue inside blood vessels. Necrosis and rupture of the convoluted tubule cells were observed in the kidneys. Further analysis of the both extracts indicated the lack of hemolytic activity, and the presence of two unknown anti-AChE substances in the AE of G. splendidum. Thus, P. galeata and G. splendidum are producers of novel toxins that affect mammals when administered orally. Full article
(This article belongs to the Special Issue Selected Papers from the 14th International Symposium on Marine Natural Products)
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Article
Hyaluromycin, a New Hyaluronidase Inhibitor of Polyketide Origin from Marine Streptomyces sp.
by Enjuro Harunari, Chiaki Imada, Yasuhiro Igarashi, Takao Fukuda, Takeshi Terahara and Takeshi Kobayashi
Mar. Drugs 2014, 12(1), 491-507; https://doi.org/10.3390/md12010491 - 21 Jan 2014
Cited by 36 | Viewed by 13459
Abstract
Hyaluromycin (1), a new member of the rubromycin family of antibiotics, was isolated from the culture extract of a marine-derived Streptomyces sp. as a HAase inhibitor on the basis of HAase activity screening. The structure of 1 was elucidated through the [...] Read more.
Hyaluromycin (1), a new member of the rubromycin family of antibiotics, was isolated from the culture extract of a marine-derived Streptomyces sp. as a HAase inhibitor on the basis of HAase activity screening. The structure of 1 was elucidated through the interpretation of NMR data for the compound and its 3″-O-methyl derivative in combination with an incorporation experiment with [1,2-13C2]acetate. The compound’s absolute configuration was determined by the comparison of its circular dichroism (CD) spectrum with those of other rubromycins. Hyaluromycin (1) consists of a γ-rubromycin core structure possessing a 2-amino-3-hydroxycyclopent-2-enone (C5N) unit as an amide substituent of the carboxyl function; both structural units have been reported only from actinomycetes. Hyaluromycin (1) displayed approximately 25-fold more potent hyaluronidase inhibitory activity against hyaluronidase than did glycyrrhizin, a known inhibitor of plant origin. Full article
(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)
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Communication
Alkaloids from the Mangrove-Derived Actinomycete Jishengella endophytica 161111
by Pei Wang, Fandong Kong, Jingjing Wei, Yi Wang, Wei Wang, Kui Hong and Weiming Zhu
Mar. Drugs 2014, 12(1), 477-490; https://doi.org/10.3390/md12010477 - 21 Jan 2014
Cited by 75 | Viewed by 9281
Abstract
A new alkaloid, 2-(furan-2-yl)-6-(2S,3S,4-trihydroxybutyl)pyrazine (1), along with 12 known compounds, 2-(furan-2-yl)-5-(2S,3S,4-trihydroxybutyl)pyrazine (2), (S)-4-isobutyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde (3), (S)-4-isopropyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde (4 [...] Read more.
A new alkaloid, 2-(furan-2-yl)-6-(2S,3S,4-trihydroxybutyl)pyrazine (1), along with 12 known compounds, 2-(furan-2-yl)-5-(2S,3S,4-trihydroxybutyl)pyrazine (2), (S)-4-isobutyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde (3), (S)-4-isopropyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde (4), (4S)-4-(2-methylbutyl)-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde (5), (S)-4-benzyl-3-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbaldehyde (6), flazin (7), perlolyrine (8), 1-hydroxy-β-carboline (9), lumichrome (10), 1H-indole-3-carboxaldehyde (11), 2-hydroxy-1-(1H-indol-3-yl)ethanone (12), and 5-(methoxymethyl)-1H-pyrrole-2-carbaldehyde (13), were isolated and identified from the fermentation broth of an endophytic actinomycetes, Jishengella endophytica 161111. The new structure 1 and the absolute configurations of 2–6 were determined by spectroscopic methods, J-based configuration analysis (JBCA) method, lactone sector rule, and electronic circular dichroism (ECD) calculations. Compounds 8–11 were active against the influenza A virus subtype H1N1 with IC50 and selectivity index (SI) values of 38.3(±1.2)/25.0(±3.6)/ 39.7(±5.6)/45.9(±2.1) μg/mL and 3.0/16.1/3.1/11.4, respectively. The IC50 and SI values of positive control, ribavirin, were 23.1(±1.7) μg/mL and 32.2, respectively. The results showed that compound 9 could be a promising new hit for anti-H1N1 drugs. The absolute configurations of 2–5, 13C nuclear magnetic resonance (NMR) data and the specific rotations of 3–6 were also reported here for the first time. Full article
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Article
Identification and Biochemical Characterization of Halisulfate 3 and Suvanine as Novel Inhibitors of Hepatitis C Virus NS3 Helicase from a Marine Sponge
by Atsushi Furuta, Kazi Abdus Salam, Idam Hermawan, Nobuyoshi Akimitsu, Junichi Tanaka, Hidenori Tani, Atsuya Yamashita, Kohji Moriishi, Masamichi Nakakoshi, Masayoshi Tsubuki, Poh Wee Peng, Youichi Suzuki, Naoki Yamamoto, Yuji Sekiguchi, Satoshi Tsuneda and Naohiro Noda
Mar. Drugs 2014, 12(1), 462-476; https://doi.org/10.3390/md12010462 - 21 Jan 2014
Cited by 13 | Viewed by 9050
Abstract
Hepatitis C virus (HCV) is an important etiological agent that is responsible for the development of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. HCV nonstructural protein 3 (NS3) helicase is a possible target for novel drug development due to its essential role in [...] Read more.
Hepatitis C virus (HCV) is an important etiological agent that is responsible for the development of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. HCV nonstructural protein 3 (NS3) helicase is a possible target for novel drug development due to its essential role in viral replication. In this study, we identified halisulfate 3 (hal3) and suvanine as novel NS3 helicase inhibitors, with IC50 values of 4 and 3 µM, respectively, from a marine sponge by screening extracts of marine organisms. Both hal3 and suvanine inhibited the ATPase, RNA binding, and serine protease activities of NS3 helicase with IC50 values of 8, 8, and 14 µM, and 7, 3, and 34 µM, respectively. However, the dengue virus (DENV) NS3 helicase, which shares a catalytic core (consisting mainly of ATPase and RNA binding sites) with HCV NS3 helicase, was not inhibited by hal3 and suvanine, even at concentrations of 100 µM. Therefore, we conclude that hal3 and suvanine specifically inhibit HCV NS3 helicase via an interaction with an allosteric site in NS3 rather than binding to the catalytic core. This led to the inhibition of all NS3 activities, presumably by inducing conformational changes. Full article
(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)
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Review
Dinophysis Toxins: Causative Organisms, Distribution and Fate in Shellfish
by Beatriz Reguera, Pilar Riobó, Francisco Rodríguez, Patricio A. Díaz, Gemita Pizarro, Beatriz Paz, José M. Franco and Juan Blanco
Mar. Drugs 2014, 12(1), 394-461; https://doi.org/10.3390/md12010394 - 20 Jan 2014
Cited by 307 | Viewed by 19662
Abstract
Several Dinophysis species produce diarrhoetic toxins (okadaic acid and dinophysistoxins) and pectenotoxins, and cause gastointestinal illness, Diarrhetic Shellfish Poisoning (DSP), even at low cell densities (<103 cells·L−1). They are the main threat, in terms of days of harvesting bans, to [...] Read more.
Several Dinophysis species produce diarrhoetic toxins (okadaic acid and dinophysistoxins) and pectenotoxins, and cause gastointestinal illness, Diarrhetic Shellfish Poisoning (DSP), even at low cell densities (<103 cells·L−1). They are the main threat, in terms of days of harvesting bans, to aquaculture in Northern Japan, Chile, and Europe. Toxicity and toxin profiles are very variable, more between strains than species. The distribution of DSP events mirrors that of shellfish production areas that have implemented toxin regulations, otherwise misinterpreted as bacterial or viral contamination. Field observations and laboratory experiments have shown that most of the toxins produced by Dinophysis are released into the medium, raising questions about the ecological role of extracelular toxins and their potential uptake by shellfish. Shellfish contamination results from a complex balance between food selection, adsorption, species-specific enzymatic transformations, and allometric processes. Highest risk areas are those combining Dinophysis strains with high cell content of okadaates, aquaculture with predominance of mytilids (good accumulators of toxins), and consumers who frequently include mussels in their diet. Regions including pectenotoxins in their regulated phycotoxins will suffer from much longer harvesting bans and from disloyal competition with production areas where these toxins have been deregulated. Full article
(This article belongs to the Special Issue Marine Shellfish Toxins)
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Article
Discovery of Novel Diterpenoids from Sinularia arborea
by Kuan-Hua Chen, Chang-Feng Dai, Tsong-Long Hwang, Chun-Yu Chen, Jan-Jung Li, Jih-Jung Chen, Yang-Chang Wu, Jyh-Horng Sheu, Wei-Hsien Wang and Ping-Jyun Sung
Mar. Drugs 2014, 12(1), 385-393; https://doi.org/10.3390/md12010385 - 17 Jan 2014
Cited by 11 | Viewed by 6077
Abstract
Two novel diterpenoids, sinularbols A (1) and B (2), which were found to possess a new carbon skeleton were isolated from the soft coral Sinularia arborea. The structures of compounds 1 and 2 were elucidated by spectroscopic methods [...] Read more.
Two novel diterpenoids, sinularbols A (1) and B (2), which were found to possess a new carbon skeleton were isolated from the soft coral Sinularia arborea. The structures of compounds 1 and 2 were elucidated by spectroscopic methods and 2 displayed a moderately inhibitory effect on the generation of superoxide anion by human neutrophils. Full article
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Article
Oxylipin Diversity in the Diatom Family Leptocylindraceae Reveals DHA Derivatives in Marine Diatoms
by Deepak Nanjappa, Giuliana D'Ippolito, Carmela Gallo, Adriana Zingone and Angelo Fontana
Mar. Drugs 2014, 12(1), 368-384; https://doi.org/10.3390/md12010368 - 17 Jan 2014
Cited by 36 | Viewed by 8180
Abstract
Marine planktonic organisms, such as diatoms, are prospective sources of novel bioactive metabolites. Oxygenated derivatives of fatty acids, generally referred to as oxylipins, in diatoms comprise a highly diverse and complex family of secondary metabolites. These molecules have recently been implicated in several [...] Read more.
Marine planktonic organisms, such as diatoms, are prospective sources of novel bioactive metabolites. Oxygenated derivatives of fatty acids, generally referred to as oxylipins, in diatoms comprise a highly diverse and complex family of secondary metabolites. These molecules have recently been implicated in several biological processes including intra- and inter-cellular signaling as well as in defense against biotic stressors and grazers. Here, we analyze the production and diversity of C20 and C22 non-volatile oxylipins in five species of the family Leptocylindraceae, which constitute a basal clade in the diatom phylogeny. We report the presence of species-specific lipoxygenase activity and oxylipin patterns, providing the first demonstration of enzymatic production of docosahexaenoic acid derivatives in marine diatoms. The differences observed in lipoxygenase pathways among the species investigated broadly reflected the relationships observed with phylogenetic markers, thus providing functional support to the taxonomic diversity of the individual species. Full article
(This article belongs to the Special Issue Metabolites in Diatoms)
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Article
Haloperoxidase Mediated Quorum Quenching by Nitzschia cf pellucida: Study of the Metabolization of N-Acyl Homoserine Lactones by a Benthic Diatom
by Michail Syrpas, Ewout Ruysbergh, Lander Blommaert, Bart Vanelslander, Koen Sabbe, Wim Vyverman, Norbert De Kimpe and Sven Mangelinckx
Mar. Drugs 2014, 12(1), 352-367; https://doi.org/10.3390/md12010352 - 17 Jan 2014
Cited by 30 | Viewed by 9804
Abstract
Diatoms are known to produce a variety of halogenated compounds, which were recently shown to have a role in allelopathic interactions between competing species. The production of these compounds is linked to haloperoxidase activity. This research, has shown that this system may also [...] Read more.
Diatoms are known to produce a variety of halogenated compounds, which were recently shown to have a role in allelopathic interactions between competing species. The production of these compounds is linked to haloperoxidase activity. This research, has shown that this system may also be involved in diatom-bacteria interactions via the H2O2 dependent inactivation of a type of quorum sensing (QS) molecule, i.e., N-β-ketoacylated homoserine lactones (AHLs), by a natural haloperoxidase system from the benthic diatom Nitzschia cf pellucida. The AHL degradation pathway towards corresponding halogenated derivatives was elucidated via HPLC-MS analysis and the synthesis of a broad series of novel halogenated AHL analogues as reference compounds. Furthermore, their biological activity as quorum sensing modulators was directly compared and evaluated against a series of naturally occurring β-keto-AHLs. It has been demonstrated that the loss of the QS activity results from the final cleavage of the halogenated N-acyl chain of the signal molecules. Full article
(This article belongs to the Special Issue Metabolites in Diatoms)
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Review
Thiopeptide Antibiotics: Retrospective and Recent Advances
by Xavier Just-Baringo, Fernando Albericio and Mercedes Álvarez
Mar. Drugs 2014, 12(1), 317-351; https://doi.org/10.3390/md12010317 - 17 Jan 2014
Cited by 145 | Viewed by 18896
Abstract
Thiopeptides, or thiazolyl peptides, are a relatively new family of antibiotics that already counts with more than one hundred different entities. Although they are mainly isolated from soil bacteria, during the last decade, new members have been isolated from marine samples. Far from [...] Read more.
Thiopeptides, or thiazolyl peptides, are a relatively new family of antibiotics that already counts with more than one hundred different entities. Although they are mainly isolated from soil bacteria, during the last decade, new members have been isolated from marine samples. Far from being limited to their innate antibacterial activity, thiopeptides have been found to possess a wide range of biological properties, including anticancer, antiplasmodial, immunosuppressive, etc. In spite of their ribosomal origin, these highly posttranslationally processed peptides have posed a fascinating synthetic challenge, prompting the development of various methodologies and strategies. Regardless of their limited solubility, intensive investigations are bringing thiopeptide derivatives closer to the clinic, where they are likely to show their veritable therapeutic potential. Full article
(This article belongs to the Special Issue Selected Papers from the 14th International Symposium on Marine Natural Products)
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Article
Chitosan-Alginate Biocomposite Containing Fucoidan for Bone Tissue Engineering
by Jayachandran Venkatesan, Ira Bhatnagar and Se-Kwon Kim
Mar. Drugs 2014, 12(1), 300-316; https://doi.org/10.3390/md12010300 - 16 Jan 2014
Cited by 244 | Viewed by 15183
Abstract
Over the last few years, significant research has been conducted in the construction of artificial bone scaffolds. In the present study, different types of polymer scaffolds, such as chitosan-alginate (Chi-Alg) and chitosan-alginate with fucoidan (Chi-Alg-fucoidan), were developed by a freeze-drying method, and each [...] Read more.
Over the last few years, significant research has been conducted in the construction of artificial bone scaffolds. In the present study, different types of polymer scaffolds, such as chitosan-alginate (Chi-Alg) and chitosan-alginate with fucoidan (Chi-Alg-fucoidan), were developed by a freeze-drying method, and each was characterized as a bone graft substitute. The porosity, water uptake and retention ability of the prepared scaffolds showed similar efficacy. The pore size of the Chi-Alg and Chi-Alg-fucoidan scaffolds were measured from scanning electron microscopy and found to be 62–490 and 56–437 µm, respectively. In vitro studies using the MG-63 cell line revealed profound cytocompatibility, increased cell proliferation and enhanced alkaline phosphatase secretion in the Chi-Alg-fucoidan scaffold compared to the Chi-Alg scaffold. Further, protein adsorption and mineralization were about two times greater in the Chi-Alg-fucoidan scaffold than the Chi-Alg scaffold. Hence, we suggest that Chi-Alg-fucoidan will be a promising biomaterial for bone tissue regeneration. Full article
(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)
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Article
The Marine Fungal Metabolite, AD0157, Inhibits Angiogenesis by Targeting the Akt Signaling Pathway
by Melissa García-Caballero, Librada Cañedo, Antonio Fernández-Medarde, Miguel Ángel Medina and Ana R. Quesada
Mar. Drugs 2014, 12(1), 279-299; https://doi.org/10.3390/md12010279 - 16 Jan 2014
Cited by 29 | Viewed by 9241
Abstract
In the course of a screening program for the inhibitors of angiogenesis from marine sources, AD0157, a pyrrolidinedione fungal metabolite, was selected for its angiosupressive properties. AD0157 inhibited the growth of endothelial and tumor cells in culture in the micromolar range. Our results [...] Read more.
In the course of a screening program for the inhibitors of angiogenesis from marine sources, AD0157, a pyrrolidinedione fungal metabolite, was selected for its angiosupressive properties. AD0157 inhibited the growth of endothelial and tumor cells in culture in the micromolar range. Our results show that subtoxic doses of this compound inhibit certain functions of endothelial cells, namely, differentiation, migration and proteolytic capability. Inhibition of the mentioned essential steps of in vitro angiogenesis is in agreement with the observed antiangiogenic activity, substantiated by using two in vivo angiogenesis models, the chorioallantoic membrane and the zebrafish embryo neovascularization assays, and by the ex vivo mouse aortic ring assay. Our data indicate that AD0157 induces apoptosis in endothelial cells through chromatin condensation, DNA fragmentation, increases in the subG1 peak and caspase activation. The data shown here altogether indicate for the first time that AD0157 displays antiangiogenic effects, both in vitro and in vivo, that are exerted partly by targeting the Akt signaling pathway in activated endothelial cells. The fact that these effects are carried out at lower concentrations than those required for other inhibitors of angiogenesis makes AD0157 a new promising drug candidate for further evaluation in the treatment of cancer and other angiogenesis-related pathologies. Full article
(This article belongs to the Collection Marine Compounds and Cancer)
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Review
Marine-Sourced Anti-Cancer and Cancer Pain Control Agents in Clinical and Late Preclinical Development
by David J. Newman and Gordon M. Cragg
Mar. Drugs 2014, 12(1), 255-278; https://doi.org/10.3390/md12010255 - 14 Jan 2014
Cited by 216 | Viewed by 18489
Abstract
The marine habitat has produced a significant number of very potent marine-derived agents that have the potential to inhibit the growth of human tumor cells in vitro and, in a number of cases, in both in vivo murine models and in humans. Although [...] Read more.
The marine habitat has produced a significant number of very potent marine-derived agents that have the potential to inhibit the growth of human tumor cells in vitro and, in a number of cases, in both in vivo murine models and in humans. Although many agents have entered clinical trials in cancer, to date, only Cytarabine, Yondelis® (ET743), Eribulin (a synthetic derivative based on the structure of halichondrin B), and the dolastatin 10 derivative, monomethylauristatin E (MMAE or vedotin) as a warhead, have been approved for use in humans (Adcetris®). In this review, we show the compounds derived from marine sources that are currently in clinical trials against cancer. We have included brief discussions of the approved agents, where they are in trials to extend their initial approved activity (a common practice once an agent is approved), and have also included an extensive discussion of the use of auristatin derivatives as warheads, plus an area that has rarely been covered, the use of marine-derived agents to ameliorate the pain from cancers in humans, and to act as an adjuvant in immunological therapies. Full article
(This article belongs to the Collection Marine Compounds and Cancer)
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Review
Holothurian Fucosylated Chondroitin Sulfate
by Vitor H. Pomin
Mar. Drugs 2014, 12(1), 232-254; https://doi.org/10.3390/md12010232 - 9 Jan 2014
Cited by 167 | Viewed by 14610
Abstract
Fucosylated chondroitin sulfate (FucCS) is a structurally distinct glycosaminoglycan found in sea cucumber species. It has the same backbone composition of alternating 4-linked glucuronic acid and 3-linked N-acetyl galactosamine residues within disaccharide repeating units as regularly found in mammalian chondroitin sulfates. However, [...] Read more.
Fucosylated chondroitin sulfate (FucCS) is a structurally distinct glycosaminoglycan found in sea cucumber species. It has the same backbone composition of alternating 4-linked glucuronic acid and 3-linked N-acetyl galactosamine residues within disaccharide repeating units as regularly found in mammalian chondroitin sulfates. However, FucCS has also sulfated fucosyl branching units 3-O-linked to the acid residues. The sulfation patterns of these branches vary accordingly with holothurian species and account for different biological actions and responses. FucCSs may exhibit anticoagulant, antithrombotic, anti-inflammatory, anticancer, antiviral, and pro-angiogenic activities, besides its beneficial effects in hemodialysis, cellular growth modulation, fibrosis and hyperglycemia. Through an historical overview, this document covers most of the science regarding the holothurian FucCS. Both structural and medical properties of this unique GAG, investigated during the last 25 years, are systematically discussed herein. Full article
(This article belongs to the Collection Bioactive Compounds from Marine Invertebrates)
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Article
First Report of a Peroxiredoxin Homologue in Jellyfish: Molecular Cloning, Expression and Functional Characterization of CcPrx4 from Cyanea capillata
by Zengliang Ruan, Guoyan Liu, Beilei Wang, Yonghong Zhou, Jia Lu, Qianqian Wang, Jie Zhao and Liming Zhang
Mar. Drugs 2014, 12(1), 214-231; https://doi.org/10.3390/md12010214 - 9 Jan 2014
Cited by 16 | Viewed by 7964
Abstract
We first identified and characterized a novel peroxiredoxin (Prx), designated as CcPrx4, from the cDNA library of the tentacle of the jellyfish Cyanea capillata. The full-length cDNA sequence of CcPrx4 consisted of 884 nucleotides with an open reading frame encoding a mature [...] Read more.
We first identified and characterized a novel peroxiredoxin (Prx), designated as CcPrx4, from the cDNA library of the tentacle of the jellyfish Cyanea capillata. The full-length cDNA sequence of CcPrx4 consisted of 884 nucleotides with an open reading frame encoding a mature protein of 247 amino acids. It showed a significant homology to peroxiredoxin 4 (Prx4) with the highly conserved F-motif (93FTFVCPTEI101), hydrophobic region (217VCPAGW222), 140GGLG143 and 239YF240, indicating that it should be a new member of the Prx4 family. The deduced CcPrx4 protein had a calculated molecular mass of 27.2 kDa and an estimated isoelectric point of 6.3. Quantitative real-time PCR analysis showed that CcPrx4 mRNA could be detected in all the jellyfish tissues analyzed. CcPrx4 protein was cloned into the expression vector, pET-24a, and expressed in Escherichia coli Rosetta (DE3) pLysS. Recombinant CcPrx4 protein was purified by HisTrap High Performance chelating column chromatography and analyzed for its biological function. The results showed that the purified recombinant CcPrx4 protein manifested the ability to reduce hydrogen peroxide and protect supercoiled DNA from oxidative damage, suggesting that CcPrx4 protein may play an important role in protecting jellyfish from oxidative damage. Full article
(This article belongs to the Collection Bioactive Compounds from Marine Invertebrates)
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Article
Inhibitory Effect of Dihydroaustrasulfone Alcohol on the Migration of Human Non-Small Cell Lung Carcinoma A549 Cells and the Antitumor Effect on a Lewis Lung Carcinoma-Bearing Tumor Model in C57BL/6J Mice
by Shuo-Chueh Chen, Yi-Chung Chien, Chun-Hsu Pan, Jyh-Horng Sheu, Chih-Yi Chen and Chieh-Hsi Wu
Mar. Drugs 2014, 12(1), 196-213; https://doi.org/10.3390/md12010196 - 9 Jan 2014
Cited by 21 | Viewed by 8921
Abstract
There are many major causes of cancer death, including metastasis of cancer. Dihydroaustrasulfone alcohol, which is isolated from marine coral, has shown antioxidant activity, but has not been reported to have an anti-cancer effect. We first discovered that dihydroaustrasulfone alcohol provided a concentration-dependent [...] Read more.
There are many major causes of cancer death, including metastasis of cancer. Dihydroaustrasulfone alcohol, which is isolated from marine coral, has shown antioxidant activity, but has not been reported to have an anti-cancer effect. We first discovered that dihydroaustrasulfone alcohol provided a concentration-dependent inhibitory effect on the migration and motility of human non-small cell lung carcinoma (NSCLC) A549 cells by trans-well and wound healing assays. The results of a zymography assay and Western blot showed that dihydroaustrasulfone alcohol suppressed the activities and protein expression of matrix metalloproteinase (MMP)-2 and MMP-9. Further investigation revealed that dihydroaustrasulfone alcohol suppressed the phosphorylation of ERK1/2, p38, and JNK1/2. Dihydroaustrasulfone alcohol also suppressed the expression of PI3K and the phosphorylation of Akt. Furthermore, dihydroaustrasulfone alcohol markedly inhibited tumor growth in Lewis lung cancer (LLC)-bearing mice. We concluded that dihydroaustrasulfone alcohol is a new pure compound with anti-migration and anti-tumor growth activity in lung cancer and might be applied to clinical treatment in the future. Full article
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407 KiB  
Book Review
Chinese Marine Materia Medica. By Huashi Guan and Shuguang Wang. Shanghai Scientific and Technical Publishers, China Ocean Press, and Chemical Industry Press: Shanghai, Beijing, China, 2009; Hardback, 7064 pp; ¥ 2920; ISBN 978-7-5323-9958-1/R•2707; ISBN 978-7-5323-9973-4/R•2708; ISBN 978-7-1220-6012-9
by Peter Proksch
Mar. Drugs 2014, 12(1), 193-195; https://doi.org/10.3390/md12010193 - 7 Jan 2014
Cited by 4 | Viewed by 6574
Abstract
China is one of the first countries to use marine materia medica for treating diseases. Ancient books on Chinese herbology, such as Shennong Bencaojing (Shennong’s Classic of Materia Medica), Xinxiu Bencao (Newly Revised Materia Medica) and Bencao Gangmu ( [...] Read more.
China is one of the first countries to use marine materia medica for treating diseases. Ancient books on Chinese herbology, such as Shennong Bencaojing (Shennong’s Classic of Materia Medica), Xinxiu Bencao (Newly Revised Materia Medica) and Bencao Gangmu (Compendium of Materia Medica), have detailed more than 110 marine herbs and thousands of marine herbal formulas (including those for Chinese food therapy). A great deal of information on marine herbs and their applications in medicine, collected over thousands of years, has provided an important foundation for modern research in the area of marine drugs. Thanks to these records and references, the research and development of modern Chinese marine drugs continue to evolve and mature. Since the middle of the 20th century, special attention has been paid to traditional Chinese medicine, resulting in a significant increase in the number of newly discovered marine herbs. Comprehensive surveys in the past have also created a wealth of data on the pharmacology, chemistry, biology and ecology of marine medicinal bioresources. After thousands of years of research, historical references to traditional marine herbs are scattered throughout ancient books, local chronicles, medical books, or monographs on medicinal herbs. Unfortunately, there is no systematic way to collate or scientifically verify these references. Furthermore, during the last century, scientists around the world have accumulated large quantities of information on marine natural products, but these are also scattered throughout academic books and journals. Full article
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1386 KiB  
Article
Stereochemistry of Complex Marine Natural Products by Quantum Mechanical Calculations of NMR Chemical Shifts: Solvent and Conformational Effects on Okadaic Acid
by Humberto J. Domínguez, Guillermo D. Crespín, Adrián J. Santiago-Benítez, José A. Gavín, Manuel Norte, José J. Fernández and Antonio Hernández Daranas
Mar. Drugs 2014, 12(1), 176-192; https://doi.org/10.3390/md12010176 - 7 Jan 2014
Cited by 22 | Viewed by 8699
Abstract
Marine organisms are an increasingly important source of novel metabolites, some of which have already inspired or become new drugs. In addition, many of these molecules show a high degree of novelty from a structural and/or pharmacological point of view. Structure determination is [...] Read more.
Marine organisms are an increasingly important source of novel metabolites, some of which have already inspired or become new drugs. In addition, many of these molecules show a high degree of novelty from a structural and/or pharmacological point of view. Structure determination is generally achieved by the use of a variety of spectroscopic methods, among which NMR (nuclear magnetic resonance) plays a major role and determination of the stereochemical relationships within every new molecule is generally the most challenging part in structural determination. In this communication, we have chosen okadaic acid as a model compound to perform a computational chemistry study to predict 1H and 13C NMR chemical shifts. The effect of two different solvents and conformation on the ability of DFT (density functional theory) calculations to predict the correct stereoisomer has been studied. Full article
(This article belongs to the Special Issue Selected Papers from the 14th International Symposium on Marine Natural Products)
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877 KiB  
Communication
Induced Marine Fungus Chondrostereum sp. as a Means of Producing New Sesquiterpenoids Chondrosterins I and J by Using Glycerol as the Carbon Source
by Hou-Jin Li, Wen-Han Jiang, Wan-Ling Liang, Jia-Xin Huang, Yu-Fei Mo, Yan-Qing Ding, Chi-Keung Lam, Xiao-Jun Qian, Xiao-Feng Zhu and Wen-Jian Lan
Mar. Drugs 2014, 12(1), 167-175; https://doi.org/10.3390/md12010167 - 7 Jan 2014
Cited by 33 | Viewed by 6988
Abstract
Chondrostereum sp., a marine fungus isolated from a soft coral Sarcophyton tortuosum, can yield hirsutane framework sesquiterpenoids. However, the metabolites profiles vary dramatically with the composition change of the culture media. This fungus was cultured in a liquid medium containing glycerol as [...] Read more.
Chondrostereum sp., a marine fungus isolated from a soft coral Sarcophyton tortuosum, can yield hirsutane framework sesquiterpenoids. However, the metabolites profiles vary dramatically with the composition change of the culture media. This fungus was cultured in a liquid medium containing glycerol as the carbon source, and two new metabolites, chondrosterins I and J (1 and 2), were obtained. Their structures were elucidated primarily based on MS, NMR and X-ray single-crystal diffraction data. By comparison with the known hirsutane sesquiterpenoids, chondrosterins I and J have unique structural features, including a methyl was migrated from C-2 to C-6, and the methyl at C-3 was carboxylated. Compound 2 exhibited potent cytotoxic activities against the cancer cell lines CNE-1 and CNE-2 with the IC50 values of 1.32 and 0.56 μM. Full article
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Review
Biochemical and Genetic Engineering of Diatoms for Polyunsaturated Fatty Acid Biosynthesis
by Hong-Ye Li, Yang Lu, Jian-Wei Zheng, Wei-Dong Yang and Jie-Sheng Liu
Mar. Drugs 2014, 12(1), 153-166; https://doi.org/10.3390/md12010153 - 7 Jan 2014
Cited by 62 | Viewed by 10685
Abstract
The role of diatoms as a source of bioactive compounds has been recently explored. Diatom cells store a high amount of fatty acids, especially certain polyunsaturated fatty acids (PUFAs). However, many aspects of diatom metabolism and the production of PUFAs remain unclear. This [...] Read more.
The role of diatoms as a source of bioactive compounds has been recently explored. Diatom cells store a high amount of fatty acids, especially certain polyunsaturated fatty acids (PUFAs). However, many aspects of diatom metabolism and the production of PUFAs remain unclear. This review describes a number of technical strategies, such as modulation of environmental factors (temperature, light, chemical composition of culture medium) and culture methods, to influence the content of PUFAs in diatoms. Genetic engineering, a newly emerging field, also plays an important role in controlling the synthesis of fatty acids in marine microalgae. Several key points in the biosynthetic pathway of PUFAs in diatoms as well as recent progresses are also a critical part and are summarized here. Full article
(This article belongs to the Special Issue Metabolites in Diatoms)
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Review
Astaxanthin: Sources, Extraction, Stability, Biological Activities and Its Commercial Applications—A Review
by Ranga Rao Ambati, Siew-Moi Phang, Sarada Ravi and Ravishankar Gokare Aswathanarayana
Mar. Drugs 2014, 12(1), 128-152; https://doi.org/10.3390/md12010128 - 7 Jan 2014
Cited by 1495 | Viewed by 77421
Abstract
There is currently much interest in biological active compounds derived from natural resources, especially compounds that can efficiently act on molecular targets, which are involved in various diseases. Astaxanthin (3,3′-dihydroxy-β, β′-carotene-4,4′-dione) is a xanthophyll carotenoid, contained in Haematococcus pluvialis, Chlorella zofingiensis, [...] Read more.
There is currently much interest in biological active compounds derived from natural resources, especially compounds that can efficiently act on molecular targets, which are involved in various diseases. Astaxanthin (3,3′-dihydroxy-β, β′-carotene-4,4′-dione) is a xanthophyll carotenoid, contained in Haematococcus pluvialis, Chlorella zofingiensis, Chlorococcum, and Phaffia rhodozyma. It accumulates up to 3.8% on the dry weight basis in H. pluvialis. Our recent published data on astaxanthin extraction, analysis, stability studies, and its biological activities results were added to this review paper. Based on our results and current literature, astaxanthin showed potential biological activity in in vitro and in vivo models. These studies emphasize the influence of astaxanthin and its beneficial effects on the metabolism in animals and humans. Bioavailability of astaxanthin in animals was enhanced after feeding Haematococcus biomass as a source of astaxanthin. Astaxanthin, used as a nutritional supplement, antioxidant and anticancer agent, prevents diabetes, cardiovascular diseases, and neurodegenerative disorders, and also stimulates immunization. Astaxanthin products are used for commercial applications in the dosage forms as tablets, capsules, syrups, oils, soft gels, creams, biomass and granulated powders. Astaxanthin patent applications are available in food, feed and nutraceutical applications. The current review provides up-to-date information on astaxanthin sources, extraction, analysis, stability, biological activities, health benefits and special attention paid to its commercial applications. Full article
(This article belongs to the Special Issue New Approaches for Activating Silent Biogenetic Gene Clusters in Marine Microorganisms)
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738 KiB  
Article
Anti-Chikungunya Viral Activities of Aplysiatoxin-Related Compounds from the Marine Cyanobacterium Trichodesmium erythraeum
by Deepak Kumar Gupta, Parveen Kaur, See Ting Leong, Lik Tong Tan, Michèle R. Prinsep and Justin Jang Hann Chu
Mar. Drugs 2014, 12(1), 115-127; https://doi.org/10.3390/md12010115 - 3 Jan 2014
Cited by 69 | Viewed by 10619
Abstract
Tropical filamentous marine cyanobacteria have emerged as a viable source of novel bioactive natural products for drug discovery and development. In the present study, aplysiatoxin (1), debromoaplysiatoxin (2) and anhydrodebromoaplysiatoxin (3), as well as two new analogues, [...] Read more.
Tropical filamentous marine cyanobacteria have emerged as a viable source of novel bioactive natural products for drug discovery and development. In the present study, aplysiatoxin (1), debromoaplysiatoxin (2) and anhydrodebromoaplysiatoxin (3), as well as two new analogues, 3-methoxyaplysiatoxin (4) and 3-methoxydebromoaplysiatoxin (5), are reported for the first time from the marine cyanobacterium Trichodesmium erythraeum. The identification of the bloom-forming cyanobacterial strain was confirmed based on phylogenetic analysis of its 16S rRNA sequences. Structural determination of the new analogues was achieved by extensive NMR spectroscopic analysis and comparison with NMR spectral data of known compounds. In addition, the antiviral activities of these marine toxins were assessed using Chikungunya virus (CHIKV)-infected cells. Post-treatment experiments using the debrominated analogues, namely compounds 2, 3 and 5, displayed dose-dependent inhibition of CHIKV when tested at concentrations ranging from 0.1 µM to 10.0 µM. Furthermore, debromoaplysiatoxin (2) and 3-methoxydebromoaplysiatoxin (5) exhibited significant anti-CHIKV activities with EC50 values of 1.3 μM and 2.7 μM, respectively, and selectivity indices of 10.9 and 9.2, respectively. Full article
(This article belongs to the Special Issue Compounds from Cyanobacteria)
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Article
Exploring Bioactive Properties of Marine Cyanobacteria Isolated from the Portuguese Coast: High Potential as a Source of Anticancer Compounds
by Margarida Costa, Mónica Garcia, João Costa-Rodrigues, Maria Sofia Costa, Maria João Ribeiro, Maria Helena Fernandes, Piedade Barros, Aldo Barreiro, Vitor Vasconcelos and Rosário Martins
Mar. Drugs 2014, 12(1), 98-114; https://doi.org/10.3390/md12010098 - 31 Dec 2013
Cited by 64 | Viewed by 14218
Abstract
The oceans remain a major source of natural compounds with potential in pharmacology. In particular, during the last few decades, marine cyanobacteria have been in focus as producers of interesting bioactive compounds, especially for the treatment of cancer. In this study, the anticancer [...] Read more.
The oceans remain a major source of natural compounds with potential in pharmacology. In particular, during the last few decades, marine cyanobacteria have been in focus as producers of interesting bioactive compounds, especially for the treatment of cancer. In this study, the anticancer potential of extracts from twenty eight marine cyanobacteria strains, belonging to the underexplored picoplanktonic genera, Cyanobium, Synechocystis and Synechococcus, and the filamentous genera, Nodosilinea, Leptolyngbya, Pseudanabaena and Romeria, were assessed in eight human tumor cell lines. First, a crude extract was obtained by dichloromethane:methanol extraction, and from it, three fractions were separated in a Si column chromatography. The crude extract and fractions were tested in eight human cancer cell lines for cell viability/toxicity, accessed with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and lactic dehydrogenase release (LDH) assays. Eight point nine percent of the strains revealed strong cytotoxicity; 17.8% showed moderate cytotoxicity, and 14.3% assays showed low toxicity. The results obtained revealed that the studied genera of marine cyanobacteria are a promising source of novel compounds with potential anticancer activity and highlight the interest in also exploring the smaller filamentous and picoplanktonic genera of cyanobacteria. Full article
(This article belongs to the Special Issue Selected Papers from the 14th International Symposium on Marine Natural Products)
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978 KiB  
Article
Invasive Lionfish (Pterois volitans): A Potential Human Health Threat for Ciguatera Fish Poisoning in Tropical Waters
by Alison Robertson, Ana C. Garcia, Harold A. Flores Quintana, Tyler B. Smith, Bernard F. Castillo II, Kynoch Reale-Munroe, Joseph A. Gulli, David A. Olsen, Jennifer I. Hooe-Rollman, Edward L. E. Jester, Brian J. Klimek and Steven M. Plakas
Mar. Drugs 2014, 12(1), 88-97; https://doi.org/10.3390/md12010088 - 27 Dec 2013
Cited by 43 | Viewed by 17860
Abstract
Invasive Indo-Pacific lionfish (Pterois volitans) have rapidly expanded in the Western Atlantic over the past decade and have had a significant negative impact on reef fish biodiversity, habitat, and community structure, with lionfish out-competing native predators for resources. In an effort [...] Read more.
Invasive Indo-Pacific lionfish (Pterois volitans) have rapidly expanded in the Western Atlantic over the past decade and have had a significant negative impact on reef fish biodiversity, habitat, and community structure, with lionfish out-competing native predators for resources. In an effort to reduce this population explosion, lionfish have been promoted for human consumption in the greater Caribbean region. This study examined whether the geographical expansion of the lionfish into a known ciguatera-endemic region can pose a human health threat for ciguatera fish poisoning (CFP). More than 180 lionfish were collected from waters surrounding the US Virgin Islands throughout 2010 and 2011. Ciguatoxin testing included an in vitro neuroblastoma cytotoxicity assay for composite toxicity assessment of sodium-channel toxins combined with confirmatory liquid chromatography tandem mass spectrometry. A 12% prevalence rate of ciguatoxic lionfish exceeding the FDA guidance level of 0.1 µg/kg C-CTX-1 equivalents was identified in fish from the U.S. Virgin Islands, highlighting a potential consumption risk in this region. This study presents the first evidence that the invasive lionfish, pose a direct human health risk for CFP and highlights the need for awareness and research on this food safety hazard in known endemic areas. Full article
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1933 KiB  
Article
Gliotoxin Isolated from Marine Fungus Aspergillus sp. Induces Apoptosis of Human Cervical Cancer and Chondrosarcoma Cells
by Van-Tinh Nguyen, Jung Suck Lee, Zhong-Ji Qian, Yong-Xin Li, Kil-Nam Kim, Soo-Jin Heo, You-Jin Jeon, Won Sun Park, Il-Whan Choi, Jae-Young Je and Won-Kyo Jung
Mar. Drugs 2014, 12(1), 69-87; https://doi.org/10.3390/md12010069 - 24 Dec 2013
Cited by 70 | Viewed by 12462
Abstract
Gliotoxin, a secondary metabolite produced by marine fungus Aspergillus sp., possesses various biological activities including anticancer activity. However, the mechanism underlying gliotoxin-induced cytotoxicity on human cervical cancer (Hela) and human chondrosarcoma (SW1353) cells remains unclear. In this study, we focused on the effect [...] Read more.
Gliotoxin, a secondary metabolite produced by marine fungus Aspergillus sp., possesses various biological activities including anticancer activity. However, the mechanism underlying gliotoxin-induced cytotoxicity on human cervical cancer (Hela) and human chondrosarcoma (SW1353) cells remains unclear. In this study, we focused on the effect of gliotoxin induction on apoptosis, the activating expressions of caspase family enzymes in the cells. Apoptotic cell levels were measured through DAPI and Annexin V/Propidium Iodide (PI) double staining analysis. The apoptotic protein expression of Bcl-2 and caspase family was detected by Western blot in Hela and SW1353 cells. Our results showed that gliotoxin treatment inhibited cell proliferation and induced significant morphological changes. Gliotoxin induced apoptosis was further confirmed by DNA fragmentation, chromatin condensation and disrupted mitochondrial membrane potential. Gliotoxin-induced activation of caspase-3, caspase-8 and caspase-9, down-regulation of Bcl-2, up-regulation of Bax and cytochromec (cyt c) release showed evidence for the gliotoxin activity on apoptosis. These findings suggest that gliotoxin isolated from marine fungus Aspergillus sp. induced apoptosis in Hela and SW1353 cells via the mitochondrial pathway followed by downstream events leading to apoptotic mode of cell death. Full article
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Article
Palmitic Acid and Ergosta-7,22-dien-3-ol Contribute to the Apoptotic Effect and Cell Cycle Arrest of an Extract from Marthasterias glacialis L. in Neuroblastoma Cells
by David M. Pereira, Georgina Correia-da-Silva, Patrícia Valentão, Natércia Teixeira and Paula B. Andrade
Mar. Drugs 2014, 12(1), 54-68; https://doi.org/10.3390/md12010054 - 24 Dec 2013
Cited by 49 | Viewed by 8749
Abstract
We describe the effect of a chemically characterized lipophilic extract obtained from Marthasterias glacialis L. against human breast cancer (MCF-7) and human neuroblastoma (SH-SY5Y) cell lines. Evaluation of DNA synthesis revealed that both cell lines were markedly affected in a concentration-dependent way, the [...] Read more.
We describe the effect of a chemically characterized lipophilic extract obtained from Marthasterias glacialis L. against human breast cancer (MCF-7) and human neuroblastoma (SH-SY5Y) cell lines. Evaluation of DNA synthesis revealed that both cell lines were markedly affected in a concentration-dependent way, the SH-SY5Y cell line being more susceptible. Cell cycle arrest was observed, an effect induced by the sterol, ergosta-7,22-dien-3-ol, present in the extract. Morphological evaluation of treated cells showed the advent of lipid droplets and chromatin condensation compatible with apoptosis, which was confirmed by the evaluation of caspase-3 and -9 activities. Palmitic acid was the main compound responsible for this apoptotic effect by a ceramide-independent mechanism that involved endoplasmic reticulum (ER)-stress with upregulation of CCAAT/-enhancer-binding protein homologous protein (CHOP). Full article
(This article belongs to the Collection Marine Compounds and Cancer)
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950 KiB  
Article
Solomonsterol A, a Marine Pregnane-X-Receptor Agonist, Attenuates Inflammation and Immune Dysfunction in a Mouse Model of Arthritis
by Andrea Mencarelli, Claudio D'Amore, Barbara Renga, Sabrina Cipriani, Adriana Carino, Valentina Sepe, Elisa Perissutti, Maria Valeria D'Auria, Angela Zampella, Eleonora Distrutti and Stefano Fiorucci
Mar. Drugs 2014, 12(1), 36-53; https://doi.org/10.3390/md12010036 - 24 Dec 2013
Cited by 28 | Viewed by 7705
Abstract
In the present study we provide evidence that solomonsterol A, a selective pregnane X receptor (PXR) agonist isolated from the marine sponge Theonella swinhoei, exerts anti-inflammatory activity and attenuates systemic inflammation and immune dysfunction in a mouse model of rheumatoid arthritis. Solomonsterol [...] Read more.
In the present study we provide evidence that solomonsterol A, a selective pregnane X receptor (PXR) agonist isolated from the marine sponge Theonella swinhoei, exerts anti-inflammatory activity and attenuates systemic inflammation and immune dysfunction in a mouse model of rheumatoid arthritis. Solomonsterol A was effective in protecting against the development of arthritis induced by injecting transgenic mice harboring a humanized PXR, with anti-collagen antibodies (CAIA) with beneficial effects on joint histopathology and local inflammatory response reducing the expression of inflammatory markers (TNFα, IFNγ and IL-17 and chemokines MIP1α and RANTES) in draining lymph nodes. Solomonsterol A rescued mice from systemic inflammation were assessed by measuring arthritis score, CRP and cytokines in the blood. In summary, the present study provides a molecular basis for the regulation of systemic local and systemic immunity by PXR agonists. Full article
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Article
6-Bromoisatin Found in Muricid Mollusc Extracts Inhibits Colon Cancer Cell Proliferation and Induces Apoptosis, Preventing Early Stage Tumor Formation in a Colorectal Cancer Rodent Model
by Babak Esmaeelian, Catherine A. Abbott, Richard K. Le Leu and Kirsten Benkendorff
Mar. Drugs 2014, 12(1), 17-35; https://doi.org/10.3390/md12010017 - 24 Dec 2013
Cited by 43 | Viewed by 10210
Abstract
Muricid molluscs are a natural source of brominated isatin with anticancer activity. The aim of this study was to examine the safety and efficacy of synthetic 6-bromoisatin for reducing the risk of early stage colorectal tumor formation. The purity of 6-bromoisatin was confirmed [...] Read more.
Muricid molluscs are a natural source of brominated isatin with anticancer activity. The aim of this study was to examine the safety and efficacy of synthetic 6-bromoisatin for reducing the risk of early stage colorectal tumor formation. The purity of 6-bromoisatin was confirmed by 1H NMR spectroscopy, then tested for in vitro and in vivo anticancer activity. A mouse model for colorectal cancer was utilized whereby colonic apoptosis and cell proliferation was measured 6 h after azoxymethane treatment by hematoxylin and immunohistochemical staining. Liver enzymes and other biochemistry parameters were measured in plasma and haematological assessment of the blood was conducted to assess potential toxic side-effects. 6-Bromoisatin inhibited proliferation of HT29 cells at IC50 223 μM (0.05 mg/mL) and induced apoptosis without increasing caspase 3/7 activity. In vivo 6-bromoisatin (0.05 mg/g) was found to significantly enhance the apoptotic index (p ≤ 0.001) and reduced cell proliferation (p ≤ 0.01) in the distal colon. There were no significant effects on mouse body weight, liver enzymes, biochemical factors or blood cells. However, 6-bromoisatin caused a decrease in the plasma level of potassium, suggesting a diuretic effect. In conclusion this study supports 6-bromoisatin in Muricidae extracts as a promising lead for prevention of colorectal cancer. Full article
(This article belongs to the Collection Marine Compounds and Cancer)
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792 KiB  
Article
Investigating Diet as the Source of Tetrodotoxin in Pleurobranchaea maculata
by Serena Khor, Susanna A. Wood, Lauren Salvitti, David I. Taylor, Janet Adamson, Paul McNabb and Stephen Craig Cary
Mar. Drugs 2014, 12(1), 1-16; https://doi.org/10.3390/md12010001 - 24 Dec 2013
Cited by 27 | Viewed by 8234
Abstract
The origin of tetrodotoxin (TTX) is highly debated; researchers have postulated either an endogenous or exogenous source with the host accumulating TTX symbiotically or via food chain transmission. The aim of this study was to determine whether the grey side-gilled sea slug ( [...] Read more.
The origin of tetrodotoxin (TTX) is highly debated; researchers have postulated either an endogenous or exogenous source with the host accumulating TTX symbiotically or via food chain transmission. The aim of this study was to determine whether the grey side-gilled sea slug (Pleurobranchaea maculata) could obtain TTX from a dietary source, and to attempt to identify this source through environmental surveys. Eighteen non-toxic P. maculata were maintained in aquariums and twelve were fed a TTX-containing diet. Three P. maculata were harvested after 1 h, 24 h, 17 days and 39 days and TTX concentrations in their stomach, gonad, mantle and remaining tissue/fluids determined using liquid chromatography-mass spectrometry. Tetrodotoxin was detected in all organs/tissue after 1 h with an average uptake of 32%. This decreased throughout the experiment (21%, 15% and 9%, respectively). Benthic surveys at sites with dense populations of toxic P. maculata detected very low or no TTX in other organisms. This study demonstrates that P. maculata can accumulate TTX through their diet. However, based on the absence of an identifiable TTX source in the environment, in concert with the extremely high TTX concentrations and short life spans of P. maculata, it is unlikely to be the sole TTX source for this species. Full article
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