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Marine Drugs
Volume 12
Issue 9
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Mar. Drugs, Volume 12, Issue 9 (September 2014) – 21 articles , Pages 4713-5088

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921 KiB  
Article
Aplysin Sensitizes Cancer Cells to TRAIL by Suppressing P38 MAPK/Survivin Pathway
by Jia Liu, Leina Ma, Ning Wu, Ge Liu, Lanhong Zheng and Xiukun Lin
Mar. Drugs 2014, 12(9), 5072-5088; https://doi.org/10.3390/md12095072 - 25 Sep 2014
Cited by 28 | Viewed by 7309
Abstract
TNF-related apoptosis-inducing ligand (TRAIL) is a tumor-selective apoptosis inducer and has been shown to be promising for treating various types of cancers. However, the application of TRAIL is greatly impeded by the resistance of cancer cells to its action. Studies show that overexpression [...] Read more.
TNF-related apoptosis-inducing ligand (TRAIL) is a tumor-selective apoptosis inducer and has been shown to be promising for treating various types of cancers. However, the application of TRAIL is greatly impeded by the resistance of cancer cells to its action. Studies show that overexpression of some critical pro-survival proteins, such as survivin, is responsible for TRAIL resistance. In this study, we found that Aplysin, a brominated compound from marine organisms, was able to restore the sensitivity of cancer cells to TRAIL both in vitro and in vivo. Aplysin was found to enhance the tumor-suppressing capacity of TRAIL on several TRAIL-resistant cancer cell lines. TRAIL-induced apoptosis was also potentiated in A549 and MCF7 cells treated with Aplysin. Survivin downregulation was identified as a mechanism by which Aplysin-mediated TRAIL sensitization of cancer cells. Furthermore, the activation of p38 MAPK was revealed in Aplysin-treated cancer cells, and its inhibitor SB203580 was able to abrogate the promoting effect of Aplysin on the response of cancer cells to TRAIL action, as evidenced by restored survivin expression, elevated cell survival and reduced apoptotic rates. In conclusion, we provided evidence that Aplysin acts as a sensitizer for TRAIL and its effect on p38 MAPK/survivin pathway may partially account for this activity. Considering its low cytotoxicity to normal cells, Aplysin may be a promising agent for cancer treatment in combination with TRAIL. Full article
(This article belongs to the Special Issue Mechanism of Action Analysis for Marine Compounds)
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Article
Chronic Toxicity Study of Neosaxitoxin in Rats
by Ramiro J. Zepeda, Manila Candiracci, Nicolas Lobos, Sebastian Lux and Hugo F. Miranda
Mar. Drugs 2014, 12(9), 5055-5071; https://doi.org/10.3390/md12095055 - 25 Sep 2014
Cited by 9 | Viewed by 7775
Abstract
Neosaxitoxin (NeoSTX) is a specific reversible blocker of voltage gated sodium channels on excitable cells. In the last decade, it has been tested in a number of interesting clinical trials, however there is still little information available on mammalian toxicity. Rats were treated [...] Read more.
Neosaxitoxin (NeoSTX) is a specific reversible blocker of voltage gated sodium channels on excitable cells. In the last decade, it has been tested in a number of interesting clinical trials, however there is still little information available on mammalian toxicity. Rats were treated for 12 weeks with doses of 1, 3 or 6 μg/kg of subcutaneous NeoSTX. At weeks 12 and 17, animals were sacrificed and blood samples collected for hematological and biochemical analysis. Organs were harvested for weight determination and histopathological assessments. The lowest acute toxicity via the intraperitoneal (ip) route was (30.35 μg/kg) and there was no significant difference between intramuscular and subcutaneous routes (11.4 and 12.41 μg/kg). The NeoSTX adiministration did not produce lethality at week 12 and after five weeks of suspension. NeoSTX 6 μg/kg ip produced reductions (p < 0.05) in body weight and food intake, and increased blood level of total and direct bilirubin, GGT and SGOT at week 12; all of these were reversed in the recovery period. NeoSTX 1 and 3 μg/kg ip did not show significant changes with the control group. Histopathological presentations were normal in all groups. This study revealed that NeoSTX is safe in vivo, giving a reliable security margin for its use like a local anesthetic. Full article
(This article belongs to the Special Issue Alkaloid Analogs)
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Article
A Feedback Mechanism to Control Apoptosis Occurs in the Digestive Gland of the Oyster Crassostrea gigas Exposed to the Paralytic Shellfish Toxins Producer Alexandrium catenella
by Jean-Luc Rolland, Walid Medhioub, Agnes Vergnes, Celina Abi-khalil, Véronique Savar, Eric Abadie, Estelle Masseret, Zouher Amzil and Mohamed Laabir
Mar. Drugs 2014, 12(9), 5035-5054; https://doi.org/10.3390/md12095035 - 25 Sep 2014
Cited by 13 | Viewed by 7237
Abstract
To better understand the effect of Paralytic Shellfish Toxins (PSTs) accumulation in the digestive gland of the Pacific oyster, Crassostrea gigas, we experimentally exposed individual oysters for 48 h to a PSTs producer, the dinoflagellate Alexandrium catenella. In comparison to the [...] Read more.
To better understand the effect of Paralytic Shellfish Toxins (PSTs) accumulation in the digestive gland of the Pacific oyster, Crassostrea gigas, we experimentally exposed individual oysters for 48 h to a PSTs producer, the dinoflagellate Alexandrium catenella. In comparison to the effect of the non-toxic Alexandrium tamarense, on the eight apoptotic related genes tested, Bax and BI.1 were significantly upregulated in oysters exposed 48 h to A. catenella. Among the five detoxification related genes tested, the expression of cytochrome P450 (CYP1A) was shown to be correlated with toxin concentration in the digestive gland of oysters exposed to the toxic dinoflagellate. Beside this, we observed a significant increase in ROS production, a decrease in caspase-3/7 activity and normal percentage of apoptotic cells in this tissue. Taken together, these results suggest a feedback mechanism, which may occur in the digestive gland where BI.1 could play a key role in preventing the induction of apoptosis by PSTs. Moreover, the expression of CYP1A, Bax and BI.1 were found to be significantly correlated to the occurrence of natural toxic events, suggesting that the expression of these genes together could be used as biomarker to assess the biological responses of oysters to stress caused by PSTs. Full article
(This article belongs to the Special Issue Marine Shellfish Toxins)
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Article
Didemnaketals F and G, New Bioactive Spiroketals from a Red Sea Ascidian Didemnum Species
by Lamiaa A. Shaala, Diaa T.A. Youssef, Sabrin R.M. Ibrahim, Gamal A. Mohamed, Jihan M. Badr, April L. Risinger and Susan L. Mooberry
Mar. Drugs 2014, 12(9), 5021-5034; https://doi.org/10.3390/md12095021 - 25 Sep 2014
Cited by 15 | Viewed by 6676
Abstract
In continuation of our ongoing efforts to identify bioactive compounds from Red Sea marine organisms, a new collection of the ascidian Didemnum species was investigated. Chromatographic fractionation and HPLC purification of the CH2Cl2 fraction of an organic extract of the [...] Read more.
In continuation of our ongoing efforts to identify bioactive compounds from Red Sea marine organisms, a new collection of the ascidian Didemnum species was investigated. Chromatographic fractionation and HPLC purification of the CH2Cl2 fraction of an organic extract of the ascidian resulted in the identification of two new spiroketals, didemnaketals F (1) and G (2). The structure determination of the compounds was completed by extensive study of 1D (1H, 13C, and DEPT) and 2D (COSY, HSQC, and HMBC) NMR experiments in addition to high-resolution mass spectral data. Didemnaketal F (1) and G (2) differ from the previously reported compounds of this class by the lack the terminal methyl ester at C-1 and the methyl functionality at C-2. Instead, 1 and 2 possess a methyl ketone moiety instead of the terminal ester. Furthermore, didemnaketal F possesses a disubstituted double bond between C-2 and C-3, while the double bond was replaced by a secondary alcohol at C-3 in didemnaketal G. In addition, they possess the unique spiroketal/hemiketal functionality which was previously reported in didemnaketal E. Didemnaketals F (1) and G (2) displayed moderate activity against HeLa cells with of IC50s of 49.9 and 14.0 µM, respectively. In addition, didemnaketal F (1) displayed potent antimicrobial activity against E. coli and C. albicans. These findings provide further insight into the biosynthetic capabilities of this ascidian and the chemical diversity as well as the biological activity of this class of compounds. Full article
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Review
Overview on Biological Activities and Molecular Characteristics of Sulfated Polysaccharides from Marine Green Algae in Recent Years
by Lingchong Wang, Xiangyu Wang, Hao Wu and Rui Liu
Mar. Drugs 2014, 12(9), 4984-5020; https://doi.org/10.3390/md12094984 - 25 Sep 2014
Cited by 197 | Viewed by 20337
Abstract
Among the three main divisions of marine macroalgae (Chlorophyta, Phaeophyta and Rhodophyta), marine green algae are valuable sources of structurally diverse bioactive compounds and remain largely unexploited in nutraceutical and pharmaceutical areas. Recently, a great deal of interest has been developed to isolate [...] Read more.
Among the three main divisions of marine macroalgae (Chlorophyta, Phaeophyta and Rhodophyta), marine green algae are valuable sources of structurally diverse bioactive compounds and remain largely unexploited in nutraceutical and pharmaceutical areas. Recently, a great deal of interest has been developed to isolate novel sulfated polysaccharides (SPs) from marine green algae because of their numerous health beneficial effects. Green seaweeds are known to synthesize large quantities of SPs and are well established sources of these particularly interesting molecules such as ulvans from Ulva and Enteromorpha, sulfated rhamnans from Monostroma, sulfated arabinogalactans from Codium, sulfated galacotans from Caulerpa, and some special sulfated mannans from different species. These SPs exhibit many beneficial biological activities such as anticoagulant, antiviral, antioxidative, antitumor, immunomodulating, antihyperlipidemic and antihepatotoxic activities. Therefore, marine algae derived SPs have great potential for further development as healthy food and medical products. The present review focuses on SPs derived from marine green algae and presents an overview of the recent progress of determinations of their structural types and biological activities, especially their potential health benefits. Full article
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Article
Additional Evidence of the Trypanocidal Action of (−)-Elatol on Amastigote Forms through the Involvement of Reactive Oxygen Species
by Vânia Cristina Desoti, Danielle Lazarin-Bidóia, Daniela Bueno Sudatti, Renato Crespo Pereira, Tania Ueda-Nakamura, Celso Vataru Nakamura and Sueli De Oliveira Silva
Mar. Drugs 2014, 12(9), 4973-4983; https://doi.org/10.3390/md12094973 - 25 Sep 2014
Cited by 9 | Viewed by 5917
Abstract
Chagas’ disease, a vector-transmitted infectious disease, is caused by the protozoa parasite Trypanosoma cruzi. Drugs that are currently available for the treatment of this disease are unsatisfactory, making the search for new chemotherapeutic agents a priority. We recently described the trypanocidal action [...] Read more.
Chagas’ disease, a vector-transmitted infectious disease, is caused by the protozoa parasite Trypanosoma cruzi. Drugs that are currently available for the treatment of this disease are unsatisfactory, making the search for new chemotherapeutic agents a priority. We recently described the trypanocidal action of (−)-elatol, extracted from the macroalga Laurencia dendroidea. However, nothing has been described about the mechanism of action of this compound on amastigotes that are involved in the chronic phase of Chagas’ disease. The goal of the present study was to evaluate the effect of (−)-elatol on the formation of superoxide anions (O2•−), DNA fragmentation, and autophagy in amastigotes of T. cruzi to elucidate the possible mechanism of the trypanocidal action of (−)-elatol. Treatment of the amastigotes with (−)-elatol increased the formation of O2•− at all concentrations of (−)-elatol assayed compared with untreated parasites. Increased fluorescence was observed in parasites treated with (−)-elatol, indicating DNA fragmentation and the formation of autophagic compartments. The results suggest that the trypanocidal action of (−)-elatol might involve the induction of the autophagic and apoptotic death pathways triggered by an imbalance of the parasite’s redox metabolism. Full article
(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)
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Review
Bioactive Compounds from Macroalgae in the New Millennium: Implications for Neurodegenerative Diseases
by Mariana Barbosa, Patrícia Valentão and Paula B. Andrade
Mar. Drugs 2014, 12(9), 4934-4972; https://doi.org/10.3390/md12094934 - 25 Sep 2014
Cited by 125 | Viewed by 15353
Abstract
Marine environment has proven to be a rich source of structurally diverse and complex compounds exhibiting numerous interesting biological effects. Macroalgae are currently being explored as novel and sustainable sources of bioactive compounds for both pharmaceutical and nutraceutical applications. Given the increasing prevalence [...] Read more.
Marine environment has proven to be a rich source of structurally diverse and complex compounds exhibiting numerous interesting biological effects. Macroalgae are currently being explored as novel and sustainable sources of bioactive compounds for both pharmaceutical and nutraceutical applications. Given the increasing prevalence of different forms of dementia, researchers have been focusing their attention on the discovery and development of new compounds from macroalgae for potential application in neuroprotection. Neuroprotection involves multiple and complex mechanisms, which are deeply related. Therefore, compounds exerting neuroprotective effects through different pathways could present viable approaches in the management of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s. In fact, several studies had already provided promising insights into the neuroprotective effects of a series of compounds isolated from different macroalgae species. This review will focus on compounds from macroalgae that exhibit neuroprotective effects and their potential application to treat and/or prevent neurodegenerative diseases. Full article
(This article belongs to the Special Issue Marine Secondary Metabolites)
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Article
Production, Characterization and Biocompatibility of Marine Collagen Matrices from an Alternative and Sustainable Source: The Sea Urchin Paracentrotus lividus
by Cristiano Di Benedetto, Alice Barbaglio, Tiziana Martinello, Valentina Alongi, Dario Fassini, Emanuele Cullorà, Marco Patruno, Francesco Bonasoro, Mario Adolfo Barbosa, Maria Daniela Candia Carnevali and Michela Sugni
Mar. Drugs 2014, 12(9), 4912-4933; https://doi.org/10.3390/md12094912 - 24 Sep 2014
Cited by 68 | Viewed by 10683
Abstract
Collagen has become a key-molecule in cell culture studies and in the tissue engineering field. Industrially, the principal sources of collagen are calf skin and bones which, however, could be associated to risks of serious disease transmission. In fact, collagen derived from alternative [...] Read more.
Collagen has become a key-molecule in cell culture studies and in the tissue engineering field. Industrially, the principal sources of collagen are calf skin and bones which, however, could be associated to risks of serious disease transmission. In fact, collagen derived from alternative and riskless sources is required, and marine organisms are among the safest and recently exploited ones. Sea urchins possess a circular area of soft tissue surrounding the mouth, the peristomial membrane (PM), mainly composed by mammalian-like collagen. The PM of the edible sea urchin Paracentrotus lividus therefore represents a potential unexploited collagen source, easily obtainable as a food industry waste product. Our results demonstrate that it is possible to extract native collagen fibrils from the PM and produce suitable substrates for in vitro system. The obtained matrices appear as a homogeneous fibrillar network (mean fibril diameter 30–400 nm and mesh < 2 μm) and display remarkable mechanical properties in term of stiffness (146 ± 48 MPa) and viscosity (60.98 ± 52.07 GPa·s). In vitro tests with horse pbMSC show a good biocompatibility in terms of overall cell growth. The obtained results indicate that the sea urchin P. lividus can be a valuable low-cost collagen source for mechanically resistant biomedical devices. Full article
(This article belongs to the Special Issue Marine Biomaterials)
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Review
Anticancer Effects of Different Seaweeds on Human Colon and Breast Cancers
by Ghislain Moussavou, Dong Hoon Kwak, Brice Wilfried Obiang-Obonou, Cyr Abel Ogandaga Maranguy, Sylvatrie-Danne Dinzouna-Boutamba, Dae Hoon Lee, Ordelia Gwenaelle Manvoudou Pissibanganga, Kisung Ko, Jae In Seo and Young Kug Choo
Mar. Drugs 2014, 12(9), 4898-4911; https://doi.org/10.3390/md12094898 - 24 Sep 2014
Cited by 104 | Viewed by 27164
Abstract
Seafoods and seaweeds represent some of the most important reservoirs of new therapeutic compounds for humans. Seaweed has been shown to have several biological activities, including anticancer activity. This review focuses on colorectal and breast cancers, which are major causes of cancer-related mortality [...] Read more.
Seafoods and seaweeds represent some of the most important reservoirs of new therapeutic compounds for humans. Seaweed has been shown to have several biological activities, including anticancer activity. This review focuses on colorectal and breast cancers, which are major causes of cancer-related mortality in men and women. It also describes various compounds extracted from a range of seaweeds that have been shown to eradicate or slow the progression of cancer. Fucoidan extracted from the brown algae Fucus spp. has shown activity against both colorectal and breast cancers. Furthermore, we review the mechanisms through which these compounds can induce apoptosis in vitro and in vivo. By considering the ability of compounds present in seaweeds to act against colorectal and breast cancers, this review highlights the potential use of seaweeds as anticancer agents. Full article
(This article belongs to the Collection Marine Compounds and Cancer)
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Article
Preliminary Characterization, Antioxidant Properties and Production of Chrysolaminarin from Marine Diatom Odontella aurita
by Song Xia, Baoyan Gao, Aifen Li, Jihai Xiong, Ziqiang Ao and Chengwu Zhang
Mar. Drugs 2014, 12(9), 4883-4897; https://doi.org/10.3390/md12094883 - 23 Sep 2014
Cited by 96 | Viewed by 9858
Abstract
A new chrysolaminarin, named CL2, with a molecular mass of 7.75 kDa, was purified from the marine diatom, Odontella aurita, using DEAE-52 cellulose anion-exchange chromatography and Sephadex G-200 gel-filtration chromatography. The monosaccharide and structural analysis revealed that CL2 was a glucan mainly [...] Read more.
A new chrysolaminarin, named CL2, with a molecular mass of 7.75 kDa, was purified from the marine diatom, Odontella aurita, using DEAE-52 cellulose anion-exchange chromatography and Sephadex G-200 gel-filtration chromatography. The monosaccharide and structural analysis revealed that CL2 was a glucan mainly composed of glucose, which was linked by the β-d-(1→3) (main chain) and β-d-(1→6) (side chain) glycosidic bond, demonstrated by infrared spectroscopy (IR) and nuclear magnetic resonance (NMR). The antioxidant activity tests revealed that the CL2 presented stronger hydroxyl radical scavenging activity with increasing concentrations, but less was effective on reducing power analysis and scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. The influences of nitrogen concentration and light intensity on chrysolaminarin production of O. aurita were further investigated in a glass column photobioreactor, and a record high chrysolaminarin productivity of 306 mg L−1 day−1 was achieved. In conclusion, the chrysolaminarin CL2 from O. aurita may be explored as a natural antioxidant agent for application in aquaculture, food and pharmaceutical areas. Full article
(This article belongs to the Collection Marine Polysaccharides)
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Article
A New Cytotoxicity Assay for Brevetoxins Using Fluorescence Microscopy
by Jennifer R. McCall, Elizabeth A. Elliott and Andrea J. Bourdelais
Mar. Drugs 2014, 12(9), 4868-4882; https://doi.org/10.3390/md12094868 - 23 Sep 2014
Cited by 14 | Viewed by 7773
Abstract
Brevetoxins are a family of ladder-framed polyether toxins produced during blooms of the marine dinoflagellate, Karenia brevis. Consumption of shellfish or finfish exposed to brevetoxins can lead to the development of neurotoxic shellfish poisoning. The toxic effects of brevetoxins are believed to [...] Read more.
Brevetoxins are a family of ladder-framed polyether toxins produced during blooms of the marine dinoflagellate, Karenia brevis. Consumption of shellfish or finfish exposed to brevetoxins can lead to the development of neurotoxic shellfish poisoning. The toxic effects of brevetoxins are believed to be due to the activation of voltage-sensitive sodium channels in cell membranes. The traditional cytotoxicity assay for detection of brevetoxins uses the Neuro-2A cell line, which must first be treated with the neurotoxins, ouabain and veratridine, in order to become sensitive to brevetoxins. In this study, we demonstrate several drawbacks of the Neuro-2A assay, which include variability for the EC50 values for brevetoxin and non-linear triphasic dose response curves. Ouabain/ veratridine-treated Neuro-2A cells do not show a typical sigmoidal dose response curve in response to brevetoxin, but rather, have a polynomial shaped curve, which makes calculating EC50 values highly variable. We describe a new fluorescence live cell imaging model, which allows for accurate calculation of cytotoxicity via nuclear staining and additional measurement of other viability parameters depending on which aspect of the cell is stained. In addition, the SJCRH30 cell line shows promise as an alternative to Neuro-2A cells for testing brevetoxins without the need for ouabain and veratridine. Full article
(This article belongs to the Special Issue Marine Dinoflagellates)
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Article
Purification of a Low Molecular Weight Fucoidan for SPECT Molecular Imaging of Myocardial Infarction
by Pierre Saboural, Frédéric Chaubet, Francois Rouzet, Faisal Al-Shoukr, Rana Ben Azzouna, Nadia Bouchemal, Luc Picton, Liliane Louedec, Murielle Maire, Lydia Rolland, Guy Potier, Dominique Le Guludec, Didier Letourneur and Cédric Chauvierre
Mar. Drugs 2014, 12(9), 4851-4867; https://doi.org/10.3390/md12094851 - 23 Sep 2014
Cited by 56 | Viewed by 8198
Abstract
Fucoidans constitute a large family of sulfated polysaccharides with several biochemical properties. A commercial fucoidan from brown algae, containing low molecular weight polysaccharidic species constituted of l-fucose, uronic acids and sulfate groups, was simply treated here with calcium acetate solution. This treatment led [...] Read more.
Fucoidans constitute a large family of sulfated polysaccharides with several biochemical properties. A commercial fucoidan from brown algae, containing low molecular weight polysaccharidic species constituted of l-fucose, uronic acids and sulfate groups, was simply treated here with calcium acetate solution. This treatment led to a purified fraction with a yield of 45%. The physicochemical characterizations of the purified fucoidan using colorimetric assay, MALLS, dRI, FT-IR, NMR, exhibited molecular weight distributions and chemical profiles similar for both fucoidans whereas the sulfate and l-fucose contents increased by 16% and 71%, respectively. The biodistribution study in rat of both compounds labeled with 99mTc evidenced a predominant renal elimination of the purified fucoidan, but the crude fucoidan was mainly retained in liver and spleen. In rat myocardial ischemia-reperfusion, we then demonstrated the better efficiency of the purified fucoidan. This purified sulfated polysaccharide appears promising for the development of molecular imaging in acute coronary syndrome. Full article
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Article
An Improved High Yield Total Synthesis and Cytotoxicity Study of the Marine Alkaloid Neoamphimedine: An ATP-Competitive Inhibitor of Topoisomerase IIα and Potent Anticancer Agent
by Linfeng Li, Adedoyin D. Abraham, Qiong Zhou, Hadi Ali, Jeremy V. O'Brien, Brayden D. Hamill, John J. Arcaroli, Wells A. Messersmith and Daniel V. LaBarbera
Mar. Drugs 2014, 12(9), 4833-4850; https://doi.org/10.3390/md12094833 - 19 Sep 2014
Cited by 11 | Viewed by 7546
Abstract
Recently, we characterized neoamphimedine (neo) as an ATP-competitive inhibitor of the ATPase domain of human Topoisomerase IIα. Thus far, neo is the only pyridoacridine with this mechanism of action. One limiting factor in the development of neo as a therapeutic agent has been [...] Read more.
Recently, we characterized neoamphimedine (neo) as an ATP-competitive inhibitor of the ATPase domain of human Topoisomerase IIα. Thus far, neo is the only pyridoacridine with this mechanism of action. One limiting factor in the development of neo as a therapeutic agent has been access to sufficient amounts of material for biological testing. Although there are two reported syntheses of neo, both require 12 steps with low overall yields (≤6%). In this article, we report an improved total synthesis of neo achieved in 10 steps with a 25% overall yield. In addition, we report an expanded cytotoxicity study using a panel of human cancer cell lines, including: breast, colorectal, lung, and leukemia. Neo displays potent cytotoxicity (nM IC50 values) in all, with significant potency against colorectal cancer (lowest IC50 = 6 nM). We show that neo is cytotoxic not cytostatic, and that neo exerts cytotoxicity by inducing G2-M cell cycle arrest and apoptosis. Full article
(This article belongs to the Special Issue Bioactivity-Focused Syntheses of Marine Natural Products and Congeners)
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Review
Synthetic Biology and Metabolic Engineering for Marine Carotenoids: New Opportunities and Future Prospects
by Chonglong Wang, Jung-Hun Kim and Seon-Won Kim
Mar. Drugs 2014, 12(9), 4810-4832; https://doi.org/10.3390/md12094810 - 17 Sep 2014
Cited by 35 | Viewed by 14129
Abstract
Carotenoids are a class of diverse pigments with important biological roles such as light capture and antioxidative activities. Many novel carotenoids have been isolated from marine organisms to date and have shown various utilizations as nutraceuticals and pharmaceuticals. In this review, we summarize [...] Read more.
Carotenoids are a class of diverse pigments with important biological roles such as light capture and antioxidative activities. Many novel carotenoids have been isolated from marine organisms to date and have shown various utilizations as nutraceuticals and pharmaceuticals. In this review, we summarize the pathways and enzymes of carotenoid synthesis and discuss various modifications of marine carotenoids. The advances in metabolic engineering and synthetic biology for carotenoid production are also reviewed, in hopes that this review will promote the exploration of marine carotenoid for their utilizations. Full article
(This article belongs to the Special Issue Marine Carotenoids (Special Issue))
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Article
Production of Avaroferrin and Putrebactin by Heterologous Expression of a Deep-Sea Metagenomic DNA
by Masaki J. Fujita and Ryuichi Sakai
Mar. Drugs 2014, 12(9), 4799-4809; https://doi.org/10.3390/md12094799 - 12 Sep 2014
Cited by 18 | Viewed by 7851
Abstract
The siderophore avaroferrin (1), an inhibitor of Vibrio swarming that was recently identified in Shewanella algae B516, was produced by heterologous expression of the biosynthetic gene cluster cloned from a deep-sea sediment metagenomic DNA, together with two analogues, bisucaberin (2 [...] Read more.
The siderophore avaroferrin (1), an inhibitor of Vibrio swarming that was recently identified in Shewanella algae B516, was produced by heterologous expression of the biosynthetic gene cluster cloned from a deep-sea sediment metagenomic DNA, together with two analogues, bisucaberin (2) and putrebactin (3). Avaroferrin (1) is a macrocyclic heterodimer of N-hydroxy-N-succinyl cadaverine (4) and N-hydroxy-N-succinyl-putrescine (5), whereas analogues 2 and 3 are homodimers of 4 and 5, respectively. Heterologous expression of two other related genes from culturable marine bacteria resulted in production of compounds 1–3, but in quite different proportions compared with production through expression of the metagenomic DNA. Full article
(This article belongs to the Special Issue Advances and New Perspectives in Marine Biotechnology)
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Article
11-epi-Sinulariolide Acetate Reduces Cell Migration and Invasion of Human Hepatocellular Carcinoma by Reducing the Activation of ERK1/2, p38MAPK and FAK/PI3K/AKT/mTOR Signaling Pathways
by Jen-Jie Lin, Jui-Hsin Su, Chi-Chu Tsai, Yi-Jen Chen, Ming-Hui Liao and Yu-Jen Wu
Mar. Drugs 2014, 12(9), 4783-4798; https://doi.org/10.3390/md12094783 - 12 Sep 2014
Cited by 53 | Viewed by 9575
Abstract
Cancer metastasis is one of the major causes of death in cancer. An active compound, 11-epi-sinulariolide acetate (11-epi-SA), isolated from the cultured soft coral Sinularia flexibilis has been examined for potential anti-cell migration and invasion effects on hepatocellular carcinoma [...] Read more.
Cancer metastasis is one of the major causes of death in cancer. An active compound, 11-epi-sinulariolide acetate (11-epi-SA), isolated from the cultured soft coral Sinularia flexibilis has been examined for potential anti-cell migration and invasion effects on hepatocellular carcinoma cells (HCC). However, the molecular mechanism of anti-migration and invasion by 11-epi-SA on HCC, along with their corresponding effects, remain poorly understood. In this study, we investigated anti-migration and invasion effects and the underlying mechanism of 11-epi-SA in HA22T cells, and discovered by trans-well migration and invasion assays that 11-epi-SA provided a concentration-dependent inhibitory effect on the migration of human HCC HA22T cells. After treatment with 11-epi-SA for 24 h, there were suppressed protein levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and urokinase-type plasminogen activator (uPA) in HA22T cells. Meanwhile, the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) and metalloproteinase-2 (TIMP-2) were increased in a concentration-dependent manner. Further investigation revealed that 11-epi-SA suppressed the phosphorylation of ERK1/2 and p38MAPK. The 11-epi-SA also suppressed the expression of the phosphorylation of FAK/PI3K/AKT/mTOR pathways. Full article
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Review
Mugilid Fish Are Sentinels of Exposure to Endocrine Disrupting Compounds in Coastal and Estuarine Environments
by Maren Ortiz-Zarragoitia, Cristina Bizarro, Iratxe Rojo-Bartolomé, Oihane Diaz De Cerio, Miren P. Cajaraville and Ibon Cancio
Mar. Drugs 2014, 12(9), 4756-4782; https://doi.org/10.3390/md12094756 - 12 Sep 2014
Cited by 35 | Viewed by 8962
Abstract
Effects on fish reproduction can result from a variety of toxicity mechanisms first operating at the molecular level. Notably, the presence in the environment of some compounds termed endocrine disrupting chemicals (EDCs) can cause adverse effects on reproduction by interfering with the endocrine [...] Read more.
Effects on fish reproduction can result from a variety of toxicity mechanisms first operating at the molecular level. Notably, the presence in the environment of some compounds termed endocrine disrupting chemicals (EDCs) can cause adverse effects on reproduction by interfering with the endocrine system. In some cases, exposure to EDCs leads to the animal feminization and male fish may develop oocytes in testis (intersex condition). Mugilid fish are well suited sentinel organisms to study the effects of reproductive EDCs in the monitoring of estuarine/marine environments. Up-regulation of aromatases and vitellogenins in males and juveniles and the presence of intersex individuals have been described in a wide array of mullet species worldwide. There is a need to develop new molecular markers to identify early feminization responses and intersex condition in fish populations, studying mechanisms that regulate gonad differentiation under exposure to xenoestrogens. Interestingly, an electrophoresis of gonad RNA, shows a strong expression of 5S rRNA in oocytes, indicating the potential of 5S rRNA and its regulating proteins to become useful molecular makers of oocyte presence in testis. Therefore, the use of these oocyte markers to sex and identify intersex mullets could constitute powerful molecular biomarkers to assess xenoestrogenicity in field conditions. Full article
(This article belongs to the Special Issue Marine Fish Endocrine Disruption)
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849 KiB  
Article
Obtaining Spheroplasts of Armored Dinoflagellates and First Single-Channel Recordings of Their Ion Channels Using Patch-Clamping
by Ilya Pozdnyakov, Olga Matantseva, Yuri Negulyaev and Sergei Skarlato
Mar. Drugs 2014, 12(9), 4743-4755; https://doi.org/10.3390/md12094743 - 5 Sep 2014
Cited by 18 | Viewed by 6913
Abstract
Ion channels are tightly involved in various aspects of cell physiology, including cell signaling, proliferation, motility, endo- and exo-cytosis. They may be involved in toxin production and release by marine dinoflagellates, as well as harmful algal bloom proliferation. So far, the patch-clamp technique, [...] Read more.
Ion channels are tightly involved in various aspects of cell physiology, including cell signaling, proliferation, motility, endo- and exo-cytosis. They may be involved in toxin production and release by marine dinoflagellates, as well as harmful algal bloom proliferation. So far, the patch-clamp technique, which is the most powerful method to study the activity of ion channels, has not been applied to dinoflagellate cells, due to their complex cellulose-containing cell coverings. In this paper, we describe a new approach to overcome this problem, based on the preparation of spheroplasts from armored bloom-forming dinoflagellate Prorocentrum minimum. We treated the cells of P. minimum with a cellulose synthesis inhibitor, 2,6-dichlorobenzonitrile (DCB), and found out that it could also induce ecdysis and arrest cell shape maintenance in these microalgae. Treatment with 100–250 µM DCB led to an acceptable 10% yield of P. minimum spheroplasts and was independent of the incubation time in the range of 1–5 days. We show that such spheroplasts are suitable for patch-clamping in the cell-attached mode and can form 1–10 GOhm patch contact with a glass micropipette, allowing recording of ion channel activity. The first single-channel recordings of dinoflagellate ion channels are presented. Full article
(This article belongs to the Special Issue Marine Dinoflagellates)
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349 KiB  
Correction
Correction: Structural Studies of the Lipopolysaccharide from the Fish Pathogen Aeromonas veronii Strain Bs19, Serotype O16. Mar. Drugs 2014, 12, 1298–1316
by Anna Turska-Szewczuk, Katarzyna A. Duda, Dominik Schwudke, Agnieszka Pekala, Alicja Kozinska and Otto Holst
Mar. Drugs 2014, 12(9), 4741-4742; https://doi.org/10.3390/md12094741 - 5 Sep 2014
Viewed by 4747
Abstract
We found one editorial mistake in our published paper [1]. In Line 2 of Table 4, the same composition of sugars is given for the C4 and C5 species (in the C5 species, one residue: 6dHexNAc has been missed). [...] Full article
(This article belongs to the Special Issue Marine Lipopolysaccharides)
192 KiB  
Article
Porphyra-334 Isolated from the Marine Algae Bangia atropurpurea: Conformational Performance for Energy Conversion
by Li-Fan Chuang, Hong-Nong Chou and Ping-Jyun Sung
Mar. Drugs 2014, 12(9), 4732-4740; https://doi.org/10.3390/md12094732 - 3 Sep 2014
Cited by 17 | Viewed by 6232
Abstract
Prophyra-334 (p-334) may play a role of energy transfer under an uncertain mechanism, and we speculate the possible model. Via 1D and 2D NMR experiments, it was simulated the correlation between dissociation and conformation of p-334. Intramolecular interactions were observed based on a [...] Read more.
Prophyra-334 (p-334) may play a role of energy transfer under an uncertain mechanism, and we speculate the possible model. Via 1D and 2D NMR experiments, it was simulated the correlation between dissociation and conformation of p-334. Intramolecular interactions were observed based on a series of changes in the 1H and 13C chemical shifts. Nuclear Overhauser effect spectroscopy experiments and molecular models in various pD conditions indicated the p-334 molecular dissociation process status. In addition, we also used Chem3D software to find the most possible molecular conformation. The relationship between the structural status and energy conversion is explained. Those are the primary results. More researches on it are highly expected in the future. Full article
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2350 KiB  
Article
Sensitivity of Neurospora crassa to a Marine-Derived Aspergillus tubingensis Anhydride Exhibiting Antifungal Activity That Is Mediated by the MAS1 Protein
by Liat Koch, Anat Lodin, Inbal Herold, Micha Ilan, Shmuel Carmeli and Oded Yarden
Mar. Drugs 2014, 12(9), 4713-4731; https://doi.org/10.3390/md12094713 - 1 Sep 2014
Cited by 29 | Viewed by 9523
Abstract
The fungus Aspergillus tubingensis (strain OY907) was isolated from the Mediterranean marine sponge Ircinia variabilis. Extracellular extracts produced by this strain were found to inhibit the growth of several fungi. Among the secreted extract components, a novel anhydride metabolite, tubingenoic anhydride A [...] Read more.
The fungus Aspergillus tubingensis (strain OY907) was isolated from the Mediterranean marine sponge Ircinia variabilis. Extracellular extracts produced by this strain were found to inhibit the growth of several fungi. Among the secreted extract components, a novel anhydride metabolite, tubingenoic anhydride A (1) as well as the known 2-carboxymethyl-3-hexylmaleic acid anhydride, asperic acid, and campyrone A and C were purified and their structure elucidated. Compound 1 and 2-carboxymethyl-3-hexylmaleic acid anhydride inhibited Neurospora crassa growth (MIC = 330 and 207 μM, respectively) and affected hyphal morphology. We produced a N. crassa mutant exhibiting tolerance to 1 and found that a yet-uncharacterized gene, designated mas-1, whose product is a cytosolic protein, confers sensitivity to this compound. The ∆mas-1 strain showed increased tolerance to sublethal concentrations of the chitin synthase inhibitor polyoxin D, when compared to the wild type. In addition, the expression of chitin synthase genes was highly elevated in the ∆mas-1 strain, suggesting the gene product is involved in cell wall biosynthesis and the novel anhydride interferes with its function. Full article
(This article belongs to the Special Issue Bioactive Compounds from Marine Microbes)
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