Marine Drugs

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Open AccessArticle

Marinopyrrole Derivatives as Potential Antibiotic Agents against Methicillin-Resistant Staphylococcus aureus (I)

by Yan Liu, Nina M. Haste, Wdee Thienphrapa, Victor Nizet, Mary Hensler and Rongshi Li

Mar. Drugs 2012, 10(4), 953-962; https://doi.org/10.3390/md10040953 - 24 Apr 2012

Cited by 20 | Viewed by 6903

Infections caused by drug-resistant pathogens are on the rise. The ongoing spread of methicillin-resistant Staphylococcus aureus (MRSA) strains exemplifies the urgent need for new antibiotics. The marine natural product, marinopyrrole A, was previously shown to have potent antibiotic activity against Gram-positive pathogens, including [...] Read more.

Infections caused by drug-resistant pathogens are on the rise. The ongoing spread of methicillin-resistant Staphylococcus aureus (MRSA) strains exemplifies the urgent need for new antibiotics. The marine natural product, marinopyrrole A, was previously shown to have potent antibiotic activity against Gram-positive pathogens, including MRSA. However, its minimum inhibitory concentration (MIC) against MRSA was increased by >500 fold in the presence of 20% human serum, thus greatly limiting therapeutic potential. Here we report our discovery of a novel derivative of marinopyrrole A, designated 1a, featuring a 2–4 fold improved MIC against MRSA and significantly less susceptibility to serum inhibition. Importantly, compound 1a displayed rapid and concentration-dependent killing of MRSA. Compared to the natural product counterpart, compound 1a provides an important natural product based scaffold for further Structure Activity Relationship (SAR) and optimization. Full article

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Open AccessArticle

Studies on the Synthesis of Derivatives of Marine-Derived Bostrycin and Their Structure-Activity Relationship against Tumor Cells

by Hong Chen, Lili Zhong, Yuhua Long, Jia Li, Jueheng Wu, Lan Liu, Shengping Chen, Yongcheng Lin, Mengfeng Li, Xun Zhu and Zhigang She

Mar. Drugs 2012, 10(4), 932-952; https://doi.org/10.3390/md10040932 - 24 Apr 2012

Cited by 35 | Viewed by 8032

Abstract

A series of new derivatives (5–29) of marine-derived bostrycin (1) were synthesized. The in vitro cytotoxic activities of all compounds were evaluated against MCF-7, MDA-MB-435, A549, HepG2, HCT-116 and MCF-10A cells using the MTT method. The compounds [...] Read more.

A series of new derivatives (5–29) of marine-derived bostrycin (1) were synthesized. The in vitro cytotoxic activities of all compounds were evaluated against MCF-7, MDA-MB-435, A549, HepG2, HCT-116 and MCF-10A cells using the MTT method. The compounds 7, 8, 22, 23, 25, 28 and 29 of the total showed comparable activity to epirubicin, the positive control, against the tested cancer cell lines. However, these compounds also exhibited cytotoxicity towards MCF-10A cells. The structure-activity relationship (SAR) of bostrycin derivatives was also discussed based on the obtained experimental data. Full article

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3759 KiB

Open AccessArticle

Structural Characterization and Anti-HSV-1 and HSV-2 Activity of Glycolipids from the Marine Algae Osmundaria obtusiloba Isolated from Southeastern Brazilian Coast

by Lauro M. De Souza, Guilherme L. Sassaki, Maria Teresa Villela Romanos and Eliana Barreto-Bergter

Mar. Drugs 2012, 10(4), 918-931; https://doi.org/10.3390/md10040918 - 23 Apr 2012

Cited by 68 | Viewed by 9900

Abstract

Glycolipids were extracted from the red alga Osmundaria obtusiloba from Southeastern Brazilian coast. The acetone insoluble material was extracted with chloroform/methanol and the lipids, enriched in glycolipids, were fractionated on a silica gel column eluted with chloroform, acetone and then methanol. Three major [...] Read more.

Glycolipids were extracted from the red alga Osmundaria obtusiloba from Southeastern Brazilian coast. The acetone insoluble material was extracted with chloroform/methanol and the lipids, enriched in glycolipids, were fractionated on a silica gel column eluted with chloroform, acetone and then methanol. Three major orcinol-positive bands were found in the acetone and methanol fractions, being detected by thin layer chromatography. The structures of the corresponding glycolipids were elucidated by ESI-MS and ¹H/¹³C NMR analysis, on the basis of their tandem-MS behavior and HSQC, TOCSY fingerprints. For the first time, the structure of sulfoquinovosyldiacylglycerol from the red alga Osmundaria obtusiloba was characterized. This molecule exhibited potent antiviral activity against HSV-1 and HSV-2 with EC₅₀ values of 42 µg/mL to HSV-1 and 12 µg/mL to HSV-2, respectively. Two other glycolipids, mono- and digalactosyldiacylglycerol, were also found in the alga, being characterized by ESI-MS/MS. The structural elucidation of algae glycolipids is a first step for a better understanding of the relation between these structures and their biological activities. Full article

(This article belongs to the Special Issue Marine Anti-infective Agents)

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Open AccessArticle

Mitochondrial Genome-Knockout Cells Demonstrate a Dual Mechanism of Action for the Electron Transport Complex I Inhibitor Mycothiazole

by Kirsten J. Meyer, A. Jonathan Singh, Alanna Cameron, An S. Tan, Dora C. Leahy, David O’Sullivan, Praneta Joshi, Anne C. La Flamme, Peter T. Northcote, Michael V. Berridge and John H. Miller

Mar. Drugs 2012, 10(4), 900-917; https://doi.org/10.3390/md10040900 - 16 Apr 2012

Cited by 12 | Viewed by 7235

Abstract

Mycothiazole, a polyketide metabolite isolated from the marine sponge Cacospongia mycofijiensis, is a potent inhibitor of metabolic activity and mitochondrial electron transport chain complex I in sensitive cells, but other cells are relatively insensitive to the drug. Sensitive cell lines (IC₅₀ [...] Read more.

Mycothiazole, a polyketide metabolite isolated from the marine sponge Cacospongia mycofijiensis, is a potent inhibitor of metabolic activity and mitochondrial electron transport chain complex I in sensitive cells, but other cells are relatively insensitive to the drug. Sensitive cell lines (IC₅₀ 0.36–13.8 nM) include HeLa, P815, RAW 264.7, MDCK, HeLa S3, 143B, 4T1, B16, and CD4/CD8 T cells. Insensitive cell lines (IC₅₀ 12.2–26.5 μM) include HL-60, LN18, and Jurkat. Thus, there is a 34,000-fold difference in sensitivity between HeLa and HL-60 cells. Some sensitive cell lines show a biphasic response, suggesting more than one mechanism of action. Mitochondrial genome-knockout ρ⁰ cell lines are insensitive to mycothiazole, supporting a conditional mitochondrial site of action. Mycothiazole is cytostatic rather than cytotoxic in sensitive cells, has a long lag period of about 12 h, and unlike the complex I inhibitor, rotenone, does not cause G₂/M cell cycle arrest. Mycothiazole decreases, rather than increases the levels of reactive oxygen species after 24 h. It is concluded that the cytostatic inhibitory effects of mycothiazole on mitochondrial electron transport function in sensitive cell lines may depend on a pre-activation step that is absent in insensitive cell lines with intact mitochondria, and that a second lower-affinity cytotoxic target may also be involved in the metabolic and growth inhibition of cells. Full article

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Open AccessArticle

Astaxanthin Treatment Reduced Oxidative Induced Pro-Inflammatory Cytokines Secretion in U937: SHP-1 as a Novel Biological Target

by Lorenza Speranza, Mirko Pesce, Antonia Patruno, Sara Franceschelli, Maria Anna de Lutiis, Alfredo Grilli and Mario Felaco

Mar. Drugs 2012, 10(4), 890-899; https://doi.org/10.3390/md10040890 - 10 Apr 2012

Cited by 105 | Viewed by 9217

Abstract

It has been suggested that oxidative stress activates various intracellular signaling pathways leading to secretion of a variety of pro-inflammatory cytokines and chemokines. SHP-1 is a protein tyrosine phosphatase (PTP) which acts as a negative regulator of immune cytokine signaling. However, intracellular hydrogen [...] Read more.

It has been suggested that oxidative stress activates various intracellular signaling pathways leading to secretion of a variety of pro-inflammatory cytokines and chemokines. SHP-1 is a protein tyrosine phosphatase (PTP) which acts as a negative regulator of immune cytokine signaling. However, intracellular hydrogen peroxide (H₂O₂), generated endogenously upon stimulation and exogenously from environmental oxidants, has been known to be involved in the process of intracellular signaling through inhibiting various PTPs, including SHP-1. In this study, we investigated the potential role of astaxanthin, an antioxidant marine carotenoid, in re-establishing SHP-1 negative regulation on pro-inflammatory cytokines secretion in U-937 cell line stimulated with oxidative stimulus. ELISA measurement suggested that ASTA treatment (10 µM) reduced pro-inflammatory cytokines secretion (IL-1β, IL-6 and TNF-α) induced through H₂O₂, (100 µM). Furthermore, this property is elicited by restoration of basal SHP-1 protein expression level and reduced NF-κB (p65) nuclear expression, as showed by western blotting experiments. Full article

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

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Open AccessCommunication

First Total Synthesis of a Naturally Occurring Iodinated 5′-Deoxyxylofuranosyl Marine Nucleoside

by Jianyun Sun, Yanhui Dou, Haixin Ding, Ruchun Yang, Qi Sun and Qiang Xiao

Mar. Drugs 2012, 10(4), 881-889; https://doi.org/10.3390/md10040881 - 10 Apr 2012

Cited by 18 | Viewed by 7708

Abstract

4-Amino-7-(5′-deoxy-β-d-xylofuranosyl)-5-iodo-pyrrolo[2,3-d]pyrimidine 1, an unusual naturally occurring marine nucleoside isolated from an ascidan, Diplosoma sp., was synthesized from d-xylose in seven steps with 28% overall yield on 10 g scale. The key step was Vorbrüggen glycosylation of 5-iodo-pyrrolo[2,3-d]pyrimidine with [...] Read more.

4-Amino-7-(5′-deoxy-β-d-xylofuranosyl)-5-iodo-pyrrolo[2,3-d]pyrimidine 1, an unusual naturally occurring marine nucleoside isolated from an ascidan, Diplosoma sp., was synthesized from d-xylose in seven steps with 28% overall yield on 10 g scale. The key step was Vorbrüggen glycosylation of 5-iodo-pyrrolo[2,3-d]pyrimidine with 5-deoxy-1, 2-O-diacetyl-3-O-benzoyl-d-xylofuranose. Its absolute configuration was confirmed. Full article

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Open AccessReview

Mass Spectrometry-Based Metabolomics to Elucidate Functions in Marine Organisms and Ecosystems

by Sophie Goulitquer, Philippe Potin and Thierry Tonon

Mar. Drugs 2012, 10(4), 849-880; https://doi.org/10.3390/md10040849 - 05 Apr 2012

Cited by 78 | Viewed by 12258

Abstract

Marine systems are very diverse and recognized as being sources of a wide range of biomolecules. This review provides an overview of metabolite profiling based on mass spectrometry (MS) approaches in marine organisms and their environments, focusing on recent advances in the field. [...] Read more.

Marine systems are very diverse and recognized as being sources of a wide range of biomolecules. This review provides an overview of metabolite profiling based on mass spectrometry (MS) approaches in marine organisms and their environments, focusing on recent advances in the field. We also point out some of the technical challenges that need to be overcome in order to increase applications of metabolomics in marine systems, including extraction of chemical compounds from different matrices and data management. Metabolites being important links between genotype and phenotype, we describe added value provided by integration of data from metabolite profiling with other layers of omics, as well as their importance for the development of systems biology approaches in marine systems to study several biological processes, and to analyze interactions between organisms within communities. The growing importance of MS-based metabolomics in chemical ecology studies in marine ecosystems is also illustrated. Full article

(This article belongs to the Special Issue Metabolomic Approaches to Marine Organisms)

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Open AccessArticle

Cerium Binding Activity of Pectins Isolated from the Seagrasses Zostera marina and Phyllospadix iwatensis

by Yuri Khotimchenko, Elena Khozhaenko, Valeri Kovalev and Maxim Khotimchenko

Mar. Drugs 2012, 10(4), 834-848; https://doi.org/10.3390/md10040834 - 05 Apr 2012

Cited by 29 | Viewed by 7994

Abstract

Cerium binding activity of three different water soluble pectin compounds of different origin was studied in a batch sorption system. The Langmuir, Freundlich and BET sorption models were adopted to describe the binding reactions between metal ions and pectin molecules. The Langmuir model [...] Read more.

Cerium binding activity of three different water soluble pectin compounds of different origin was studied in a batch sorption system. The Langmuir, Freundlich and BET sorption models were adopted to describe the binding reactions between metal ions and pectin molecules. The Langmuir model provided the best fit. Within the pH range from 4.0 to 6.0, the largest amount of the cerium ions was bound by pectin isolated from the seagrass Phylospadix iwatensis in comparison to pectin extracted from the seagrass Zostera marina and pectin obtained from citrus peel (commercial grade). The Langmuir constants were also highest for the pectin samples isolated from the seagrass P. iwatensis. The results obtained from this study suggest that pectin is a prospective source for the development of radioisotope-removing pharmaceuticals. Full article

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Open AccessReview

Marine Bioactives: Pharmacological Properties and Potential Applications against Inflammatory Diseases

by Nicolantonio D’Orazio, Maria Alessandra Gammone, Eugenio Gemello, Massimo De Girolamo, Salvatore Cusenza and Graziano Riccioni

Mar. Drugs 2012, 10(4), 812-833; https://doi.org/10.3390/md10040812 - 05 Apr 2012

Cited by 123 | Viewed by 11621

Abstract

Inflammation is a hot topic in medical research, because it plays a key role in inflammatory diseases: rheumatoid arthritis (RA) and other forms of arthritis, diabetes, heart diseases, irritable bowel syndrome, Alzheimer’s disease, Parkinson’s disease, allergies, asthma, even cancer and many others. Over [...] Read more.

Inflammation is a hot topic in medical research, because it plays a key role in inflammatory diseases: rheumatoid arthritis (RA) and other forms of arthritis, diabetes, heart diseases, irritable bowel syndrome, Alzheimer’s disease, Parkinson’s disease, allergies, asthma, even cancer and many others. Over the past few decades, it was realized that the process of inflammation is virtually the same in different disorders, and a better understanding of inflammation may lead to better treatments for numerous diseases. Inflammation is the activation of the immune system in response to infection, irritation, or injury, with an influx of white blood cells, redness, heat, swelling, pain, and dysfunction of the organs involved. Although the pathophysiological basis of these conditions is not yet fully understood, reactive oxygen species (ROS) have often been implicated in their pathogenesis. In fact, in inflammatory diseases the antioxidant defense system is compromised, as evidenced by increased markers of oxidative stress, and decreased levels of protective antioxidant enzymes in patients with rheumatoid arthritis (RA). An enriched diet containing antioxidants, such as vitamin E, vitamin C, β-carotene and phenolic substances, has been suggested to improve symptoms by reducing disease-related oxidative stress. In this respect, the marine world represents a largely untapped reserve of bioactive ingredients, and considerable potential exists for exploitation of these bioactives as functional food ingredients. Substances such as n-3 oils, carotenoids, vitamins, minerals and peptides provide a myriad of health benefits, including reduction of cardiovascular diseases, anticarcinogenic and anti-inflammatory activities. New marine bioactives are recently gaining attention, since they could be helpful in combating chronic inflammatory degenerative conditions. The aim of this review is to examine the published studies concerning the potential pharmacological properties and application of many marine bioactives against inflammatory diseases. Full article

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

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Open AccessReview

Fucanomics and Galactanomics: Marine Distribution, Medicinal Impact, Conceptions, and Challenges

by Vitor H. Pomin

Mar. Drugs 2012, 10(4), 793-811; https://doi.org/10.3390/md10040793 - 29 Mar 2012

Cited by 64 | Viewed by 8628

Abstract

Glycomics turned out to be a very extensive project where its subdivision is consequently emerging. This is seen by the growing number of terminologies used to define subprojects concerning particular classes of bioactive carbohydrates. Sulfated fucans (SFs) and sulfated galactans (SGs) are relatively [...] Read more.

Glycomics turned out to be a very extensive project where its subdivision is consequently emerging. This is seen by the growing number of terminologies used to define subprojects concerning particular classes of bioactive carbohydrates. Sulfated fucans (SFs) and sulfated galactans (SGs) are relatively new classes of sulfated polysaccharides (SPs) that occur mostly in marine organisms, and exhibit a broad range of medicinal effects. Their structures are taxonomically dependent, and their therapeutic actions include benefits in inflammation, coagulation, thrombosis, angiogenesis, cancer, oxidation, and infections. Some red algae, marine angiosperm and invertebrates express SPs of unique structures composed of regular repeating oligomeric units of well-defined sulfation patterns. This fine pattern of structural regularity is quite rare among any naturally occurring long SPs, and enables accurate structure-biofunction correlations. Seeing that, fucanomics and galactanomics may comprise distinguished glycomics subprojects. We hereby discuss the relevance that justifies the international recognition of these subprojects in the current glycomics age associated with the beneficial outcomes that these glycans may offer in drug development. Full article

(This article belongs to the Special Issue Marine Glycoconjugates)

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Open AccessArticle

Diatom Derived Polyunsaturated Aldehydes Do Not Structure the Planktonic Microbial Community in a Mesocosm Study

by Carsten Paul, Anna Reunamo, Elin Lindehoff, Johanna Bergkvist, Michaela A. Mausz, Henrik Larsson, Hannes Richter, Sten-Åke Wängberg, Piia Leskinen, Ulf Båmstedt and Georg Pohnert

Mar. Drugs 2012, 10(4), 775-792; https://doi.org/10.3390/md10040775 - 28 Mar 2012

Cited by 24 | Viewed by 7823

Abstract

Several marine and freshwater diatoms produce polyunsaturated aldehydes (PUA) in wound-activated processes. These metabolites are also released by intact diatom cells during algal blooms. Due to their activity in laboratory experiments, PUA are considered as potential mediators of diatom-bacteria interactions. Here, we tested [...] Read more.

Several marine and freshwater diatoms produce polyunsaturated aldehydes (PUA) in wound-activated processes. These metabolites are also released by intact diatom cells during algal blooms. Due to their activity in laboratory experiments, PUA are considered as potential mediators of diatom-bacteria interactions. Here, we tested the hypothesis that PUA mediate such processes in a close-to-field mesocosm experiment. Natural plankton communities enriched with Skeletonema marinoi strains that differ in their PUA production, a plankton control, and a plankton control supplemented with PUA at natural and elevated concentrations were observed. We monitored bacterial and viral abundance as well as bacterial community composition and did not observe any influence of PUA on these parameters even at elevated concentrations. We rather detected an alternation of the bacterial diversity over time and differences between the two S. marinoi strains, indicating unique dynamic bacterial communities in these algal blooms. These results suggest that factors other than PUA are of significance for interactions between diatoms and bacteria. Full article

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Open AccessArticle

Epigenetic Tailoring for the Production of Anti-Infective Cytosporones from the Marine Fungus Leucostoma persoonii

by Jeremy Beau, Nida Mahid, Whittney N. Burda, Lacey Harrington, Lindsey N. Shaw, Tina Mutka, Dennis E. Kyle, Betty Barisic, Alberto Van Olphen and Bill J. Baker

Mar. Drugs 2012, 10(4), 762-774; https://doi.org/10.3390/md10040762 - 28 Mar 2012

Cited by 86 | Viewed by 10441

Abstract

Recent genomic studies have demonstrated that fungi can possess gene clusters encoding for the production of previously unobserved secondary metabolites. Activation of these attenuated or silenced genes to obtain either improved titers of known compounds or new ones altogether has been a subject [...] Read more.

Recent genomic studies have demonstrated that fungi can possess gene clusters encoding for the production of previously unobserved secondary metabolites. Activation of these attenuated or silenced genes to obtain either improved titers of known compounds or new ones altogether has been a subject of considerable interest. In our efforts to discover new chemotypes that are effective against infectious diseases, including malaria and methicillin-resistant Staphylococcus aureus (MRSA), we have isolated a strain of marine fungus, Leucostoma persoonii, that produces bioactive cytosporones. Epigenetic modifiers employed to activate secondary metabolite genes resulted in enhanced production of known cytosporones B (1, 360%), C (2, 580%) and E (3, 890%), as well as the production of the previously undescribed cytosporone R (4). Cytosporone E was the most bioactive, displaying an IC₉₀ of 13 µM toward Plasmodium falciparum, with A549 cytotoxicity IC₉₀ of 437 µM, representing a 90% inhibition therapeutic index (TI₉₀ = IC₉₀ A459/IC₉₀ P. falciparum) of 33. In addition, cytosporone E was active against MRSA with a minimal inhibitory concentration (MIC) of 72 µM and inhibition of MRSA biofilm at roughly half that value (minimum biofilm eradication counts, MBEC90, was found to be 39 µM). Full article

(This article belongs to the Special Issue Marine Anti-infective Agents)

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Open AccessArticle

Inhibition of Hepatitis C Virus Replication and Viral Helicase by Ethyl Acetate Extract of the Marine Feather Star Alloeocomatella polycladia

by Atsuya Yamashita, Kazi Abdus Salam, Atsushi Furuta, Yasuyoshi Matsuda, Osamu Fujita, Hidenori Tani, Yoshihisa Fujita, Yuusuke Fujimoto, Masanori Ikeda, Nobuyuki Kato, Naoya Sakamoto, Shinya Maekawa, Nobuyuki Enomoto, Masamichi Nakakoshi, Masayoshi Tsubuki, Yuji Sekiguchi, Satoshi Tsuneda, Nobuyoshi Akimitsu, Naohiro Noda, Junichi Tanaka and Kohji Moriishi Show full author list Hide full author list

Mar. Drugs 2012, 10(4), 744-761; https://doi.org/10.3390/md10040744 - 28 Mar 2012

Cited by 16 | Viewed by 8970

Abstract

Hepatitis C virus (HCV) is a causative agent of acute and chronic hepatitis, leading to the development of hepatic cirrhosis and hepatocellular carcinoma. We prepared extracts from 61 marine organisms and screened them by an in vitro fluorescence assay targeting the viral helicase [...] Read more.

Hepatitis C virus (HCV) is a causative agent of acute and chronic hepatitis, leading to the development of hepatic cirrhosis and hepatocellular carcinoma. We prepared extracts from 61 marine organisms and screened them by an in vitro fluorescence assay targeting the viral helicase (NS3), which plays an important role in HCV replication, to identify effective candidates for anti-HCV agents. An ethyl acetate-soluble fraction of the feather star Alloeocomatella polycladia exhibited the strongest inhibition of NS3 helicase activity, with an IC₅₀ of 11.7 µg/mL. The extract of A. polycladia inhibited interaction between NS3 and RNA but not ATPase of NS3. Furthermore, the replication of the replicons derived from three HCV strains of genotype 1b in cultured cells was suppressed by the extract with an EC₅₀ value of 23 to 44 µg/mL, which is similar to the IC₅₀ value of the NS3 helicase assay. The extract did not induce interferon or inhibit cell growth. These results suggest that the unknown compound(s) included in A. polycladia can inhibit HCV replication by suppressing the helicase activity of HCV NS3. This study may present a new approach toward the development of a novel therapy for chronic hepatitis C. Full article

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Open AccessArticle

A Lactose-Binding Lectin from the Marine Sponge Cinachyrella Apion (Cal) Induces Cell Death in Human Cervical Adenocarcinoma Cells

by Luciana Rabelo, Norberto Monteiro, Raphael Serquiz, Paula Santos, Ruth Oliveira, Adeliana Oliveira, Hugo Rocha, Ana Heloneida Morais, Adriana Uchoa and Elizeu Santos

Mar. Drugs 2012, 10(4), 727-743; https://doi.org/10.3390/md10040727 - 28 Mar 2012

Cited by 45 | Viewed by 8817

Abstract

Cancer represents a set of more than 100 diseases, including malignant tumors from different locations. Strategies inducing differentiation have had limited success in the treatment of established cancers. Marine sponges are a biological reservoir of bioactive molecules, especially lectins. Several animal and plant [...] Read more.

Cancer represents a set of more than 100 diseases, including malignant tumors from different locations. Strategies inducing differentiation have had limited success in the treatment of established cancers. Marine sponges are a biological reservoir of bioactive molecules, especially lectins. Several animal and plant lectins were purified with antitumor activity, mitogenic, anti-inflammatory and antiviral, but there are few reports in the literature describing the mechanism of action of lectins purified from marine sponges to induce apoptosis in human tumor cells. In this work, a lectin purified from the marine sponge Cinachyrella apion (CaL) was evaluated with respect to its hemolytic, cytotoxic and antiproliferative properties, besides the ability to induce cell death in tumor cells. The antiproliferative activity of CaL was tested against HeLa, PC3 and 3T3 cell lines, with highest growth inhibition for HeLa, reducing cell growth at a dose dependent manner (0.5–10 µg/mL). Hemolytic activity and toxicity against peripheral blood cells were tested using the concentration of IC₅₀ (10 µg/mL) for both trials and twice the IC₅₀ for analysis in flow cytometry, indicating that CaL is not toxic to these cells. To assess the mechanism of cell death caused by CaL in HeLa cells, we performed flow cytometry and western blotting. Results showed that lectin probably induces cell death by apoptosis activation by pro-apoptotic protein Bax, promoting mitochondrial membrane permeabilization, cell cycle arrest in S phase and acting as both dependent and/or independent of caspases pathway. These results indicate the potential of CaL in studies of medicine for treating cancer. Full article

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Open AccessArticle

New Gastropod Vectors and Tetrodotoxin Potential Expansion in Temperate Waters of the Atlantic Ocean

by Marisa Silva, Joana Azevedo, Paula Rodriguez, Amparo Alfonso, Luis M. Botana and Vítor Vasconcelos

Mar. Drugs 2012, 10(4), 712-726; https://doi.org/10.3390/md10040712 - 26 Mar 2012

Cited by 88 | Viewed by 9549

Abstract

Tetrodotoxin is a potent low weight marine toxin found in warm waters, especially of the Indian and Pacific Oceans. Intoxications are usually linked to the consumption of the puffer fish, although TTX was already detected in several different edible taxa. Benthic organisms such [...] Read more.

Tetrodotoxin is a potent low weight marine toxin found in warm waters, especially of the Indian and Pacific Oceans. Intoxications are usually linked to the consumption of the puffer fish, although TTX was already detected in several different edible taxa. Benthic organisms such as mollusks and echinoderms, with different feeding habits, were collected monthly along the Portuguese coast from the summer of 2009 until the end of 2010. The extraction and analysis techniques were optimized and TTX and some analogues were detected for the first time in two intertidal gastropod species—Gibbula umbilicalis and Monodonta lineata by LC-MS/MS and UPLC-MS/MS. Although the levels are low, these findings suggest that monitoring of TTX and analogues in North Atlantic species should be implemented so as to detect potentially new toxin vectors and seasonal and/or geographical patterns. Full article

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Open AccessArticle

A Marine Anthraquinone SZ-685C Overrides Adriamycin-Resistance in Breast Cancer Cells through Suppressing Akt Signaling

by Xun Zhu, Zhenjian He, Jueheng Wu, Jie Yuan, Weitao Wen, Yiwen Hu, Yi Jiang, Cuiji Lin, Qianhui Zhang, Min Lin, Henan Zhang, Wan Yang, Hong Chen, Lili Zhong, Zhigang She, Shengping Chen, Yongcheng Lin and Mengfeng Li

Mar. Drugs 2012, 10(4), 694-711; https://doi.org/10.3390/md10040694 - 23 Mar 2012

Cited by 34 | Viewed by 9195

Abstract

Breast cancer remains a major health problem worldwide. While chemotherapy represents an important therapeutic modality against breast cancer, limitations in the clinical use of chemotherapy remain formidable because of chemoresistance. The HER2/PI-3K/Akt pathway has been demonstrated to play a causal role in conferring [...] Read more.

Breast cancer remains a major health problem worldwide. While chemotherapy represents an important therapeutic modality against breast cancer, limitations in the clinical use of chemotherapy remain formidable because of chemoresistance. The HER2/PI-3K/Akt pathway has been demonstrated to play a causal role in conferring a broad chemoresistance in breast cancer cells and thus justified to be a target for enhancing the effects of anti-breast cancer chemotherapies, such as adriamycin (ADR). Agents that can either enhance the effects of chemotherapeutics or overcome chemoresistance are urgently needed for the treatment of breast cancer. In this context, SZ-685C, an agent that has been previously shown, as such, to suppress Akt signaling, is expected to increase the efficacy of chemotherapy. Our current study investigated whether SZ-685C can override chemoresistance through inhibiting Akt signaling in human breast cancer cells. ADR-resistant cells derived from human breast cancer cell lines MCF-7, MCF-7/ADR and MCF-7/Akt, were used as models to test the effects of SZ-685C. We found that SZ-685C suppressed the Akt pathway and induced apoptosis in MCF-7/ADR and MCF-7/Akt cells that are resistant to ADR treatment, leading to antitumor effects both in vitro and in vivo. Our data suggest that use of SZ-685C might represent a potentially promising approach to the treatment of ADR-resistant breast cancer. Full article

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Open AccessArticle

Temporal Trends in the Secondary Metabolite Production of the Sponge Aplysina aerophoba

by Oriol Sacristán-Soriano, Bernard Banaigs and Mikel A. Becerro

Mar. Drugs 2012, 10(4), 677-693; https://doi.org/10.3390/md10040677 - 23 Mar 2012

Cited by 38 | Viewed by 7520

Abstract

Temporal changes in the production of secondary metabolites are far from being fully understood. Our study quantified, over a two-year period, the concentrations of brominated alkaloids in the ectosome and the choanosome of Aplysina aerophoba, and examined the temporal patterns of these [...] Read more.

Temporal changes in the production of secondary metabolites are far from being fully understood. Our study quantified, over a two-year period, the concentrations of brominated alkaloids in the ectosome and the choanosome of Aplysina aerophoba, and examined the temporal patterns of these natural products. Based on standard curves, we quantified the concentrations of aerophobin-2, aplysinamisin-1, and isofistularin-3: three of the four major peaks obtained through chemical profiling with high-performance liquid chromatography. Our results showed a striking variation in compound abundance between the outer and inner layers of the sponge. The ectosome showed high concentrations of bromocompounds during the summer months, while the choanosome followed no pattern. Additionally, we found that, from the outer layer of the sponge, aerophobin-2 and isofistularin-3 were significantly correlated with water temperature. The present study is one of the first to document quantitative seasonal variations in individual compounds over multiple years. Further studies will clarify the role of environmental, biological, and physiological factors in determining the seasonal patterns in the concentration of brominated alkaloids. Full article

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Mar. Drugs, Volume 10, Issue 4 (April 2012) – 17 articles , Pages 677-962

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