Marine Drugs

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Open AccessArticle

ω-Conotoxin GVIA Mimetics that Bind and Inhibit Neuronal Ca_v2.2 Ion Channels

by Charlotte Elisabet Tranberg, Aijun Yang, Irina Vetter, Jeffrey R. McArthur, Jonathan B. Baell, Richard J. Lewis, Kellie L. Tuck and Peter J. Duggan

Mar. Drugs 2012, 10(10), 2349-2368; https://doi.org/10.3390/md10102349 - 22 Oct 2012

Cited by 19 | Viewed by 8538

Abstract

The neuronal voltage-gated N-type calcium channel (Ca_v2.2) is a validated target for the treatment of neuropathic pain. A small library of anthranilamide-derived ω-Conotoxin GVIA mimetics bearing the diphenylmethylpiperazine moiety were prepared and tested using three experimental measures of calcium channel blockade. [...] Read more.

The neuronal voltage-gated N-type calcium channel (Ca_v2.2) is a validated target for the treatment of neuropathic pain. A small library of anthranilamide-derived ω-Conotoxin GVIA mimetics bearing the diphenylmethylpiperazine moiety were prepared and tested using three experimental measures of calcium channel blockade. These consisted of a ¹²⁵I-ω-conotoxin GVIA displacement assay, a fluorescence-based calcium response assay with SH-SY5Y neuroblastoma cells, and a whole-cell patch clamp electrophysiology assay with HEK293 cells stably expressing human Ca_v2.2 channels. A subset of compounds were active in all three assays. This is the first time that compounds designed to be mimics of ω-conotoxin GVIA and found to be active in the ¹²⁵I-ω-conotoxin GVIA displacement assay have also been shown to block functional ion channels in a dose-dependent manner. Full article

(This article belongs to the Special Issue Marine Peptides and Their Mimetics)

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388 KiB

Open AccessArticle

Effects of Oral Administration of Fucoidan Extracted from Cladosiphon okamuranus on Tumor Growth and Survival Time in a Tumor-Bearing Mouse Model

by Kazuo Azuma, Toshitsugu Ishihara, Hiroyuki Nakamoto, Takao Amaha, Tomohiro Osaki, Takeshi Tsuka, Tomohiro Imagawa, Saburo Minami, Osamu Takashima, Shinsuke Ifuku, Minoru Morimoto, Hiroyuki Saimoto, Hitoshi Kawamoto and Yoshiharu Okamoto

Mar. Drugs 2012, 10(10), 2337-2348; https://doi.org/10.3390/md10102337 - 22 Oct 2012

Cited by 61 | Viewed by 10125

Abstract

We evaluated the anti-tumor activities of the oral administration of fucoidan extracted from Cladosiphon okamuranus using a tumor (colon 26)-bearing mouse model. The materials used included low-molecular-weight fucoidan (LMWF: 6.5–40 kDa), intermediate-molecular-weight fucoidan (IMWF: 110–138 kDa) and high-molecular-weight fucoidan (HMWF: 300–330 kDa). [...] Read more.

We evaluated the anti-tumor activities of the oral administration of fucoidan extracted from Cladosiphon okamuranus using a tumor (colon 26)-bearing mouse model. The materials used included low-molecular-weight fucoidan (LMWF: 6.5–40 kDa), intermediate-molecular-weight fucoidan (IMWF: 110–138 kDa) and high-molecular-weight fucoidan (HMWF: 300–330 kDa). The IMWF group showed significantly suppressed tumor growth. The LMWF and HMWF groups showed significantly increased survival times compared with that observed in the control group (mice fed a fucoidan-free diet). The median survival times in the control, LMWF, IMWF and HMWF groups were 23, 46, 40 and 43 days, respectively. It was also found that oral administration of fucoidan increased the population of natural killer cells in the spleen. Furthermore, from the results of the experiment using Myd-88 knockout mice, it was found that these effects are related to gut immunity. These results suggest that fucoidan is a candidate anti-tumor functional food. Full article

(This article belongs to the Special Issue Marine Glycoconjugates)

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309 KiB

Open AccessArticle

Polymethoxy-1-alkenes from Aphanizomenon ovalisporum Inhibit Vertebrate Development in the Zebrafish (Danio rerio) Embryo Model

by Asha Jaja-Chimedza, Miroslav Gantar, Patrick D. L. Gibbs, Michael C. Schmale and John P. Berry

Mar. Drugs 2012, 10(10), 2322-2336; https://doi.org/10.3390/md10102322 - 22 Oct 2012

Cited by 13 | Viewed by 7132

Abstract

Cyanobacteria are recognized producers of a wide array of toxic or otherwise bioactive secondary metabolites. The present study utilized the zebrafish (Danio rerio) embryo as an aquatic animal model of vertebrate development to identify, purify and characterize lipophilic inhibitors of development [...] Read more.

Cyanobacteria are recognized producers of a wide array of toxic or otherwise bioactive secondary metabolites. The present study utilized the zebrafish (Danio rerio) embryo as an aquatic animal model of vertebrate development to identify, purify and characterize lipophilic inhibitors of development (i.e., developmental toxins) from an isolate of the freshwater cyanobacterial species, Aphanizomenon ovalisporum. Bioassay-guided fractionation led to the purification, and subsequent chemical characterization, of an apparent homologous series of isotactic polymethoxy-1-alkenes (1–6), including three congeners (4–6) previously identified from the strain, and two variants previously identified from other species (2 and 3), as well as one apparently novel member of the series (1). Five of the PMAs in the series (1–5) were purified in sufficient quantity for comparative toxicological characterization, and toxicity in the zebrafish embryo model was found to generally correlate with relative chain length and/or methoxylation. Moreover, exposure of embryos to a combination of variants indicates an apparent synergistic interaction between the congeners. Although PMAs have been identified previously in cyanobacteria, this is the first report of their apparent toxicity. These results, along with the previously reported presence of the PMAs from several cyanobacterial species, suggest a possibly widespread distribution of the PMAs as toxic secondary metabolites and warrants further chemical and toxicological investigation. Full article

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Open AccessReview

Current Status on Marine Products with Reversal Effect on Cancer Multidrug Resistance

by Ioana Abraham, Khalid El Sayed, Zhe-Sheng Chen and Huiqin Guo

Mar. Drugs 2012, 10(10), 2312-2321; https://doi.org/10.3390/md10102312 - 19 Oct 2012

Cited by 63 | Viewed by 8818

Abstract

The resistance of tumor cells to a broad range of anticancer agents continues to be a problem for the success of cancer chemotherapy. Multidrug resistance (MDR) is due in part to three drug transporter proteins: ABCB1/P-glycoprotein (P-gp), ABCC1/multidrug resistance protein 1 (MRP1) and [...] Read more.

The resistance of tumor cells to a broad range of anticancer agents continues to be a problem for the success of cancer chemotherapy. Multidrug resistance (MDR) is due in part to three drug transporter proteins: ABCB1/P-glycoprotein (P-gp), ABCC1/multidrug resistance protein 1 (MRP1) and ABCG2/breast cancer resistance protein (BCRP). These transporters are part of the ATP-binding cassette (ABC) superfamily, whose members function as ATP-dependent drug-efflux pumps. Their activity can be blocked by various drugs such as verapamil (calcium channel blocker) and cyclosporin A (immunosuppressive agent), etc. These compounds are called MDR modulators or reversals. This review highlights several marine natural products with reversal effect on multidrug resistance in cancer, including agosterol A, ecteinascidin 743, sipholane triterpenoids, bryostatin 1, and welwitindolinones. Full article

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Open AccessArticle

Ammonificins C and D, Hydroxyethylamine Chromene Derivatives from a Cultured Marine Hydrothermal Vent Bacterium, Thermovibrio ammonificans

by Eric H. Andrianasolo, Liti Haramaty, Richard Rosario-Passapera, Costantino Vetriani, Paul Falkowski, Eileen White and Richard Lutz

Mar. Drugs 2012, 10(10), 2300-2311; https://doi.org/10.3390/md10102300 - 19 Oct 2012

Cited by 20 | Viewed by 6775

Abstract

Chemical and biological investigation of the cultured marine hydrothermal vent bacterium, Thermovibrio ammonifican led to the isolation of two hydroxyethylamine chromene derivatives, ammonificins C and D. Their structures were elucidated using combination of NMR and mass spectrometry. Absolute stereochemistry was ascertained by comparison [...] Read more.

Chemical and biological investigation of the cultured marine hydrothermal vent bacterium, Thermovibrio ammonifican led to the isolation of two hydroxyethylamine chromene derivatives, ammonificins C and D. Their structures were elucidated using combination of NMR and mass spectrometry. Absolute stereochemistry was ascertained by comparison of experimental and calculated CD spectra. Biological evaluation and assessment were determined using the patented ApopScreen cell-based screen for apoptosis-induction. Ammonificins C and D induce apoptosis in micromolar concentrations. To our knowledge, this finding is the first report of chemical compounds that induce apoptosis from the cultured deep-sea marine organism, hydrothermal vent bacterium, Thermovibrio ammonificans. Full article

(This article belongs to the Special Issue Deep-Sea Natural Products)

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Open AccessArticle

Assessment of the Bacteriocinogenic Potential of Marine Bacteria Reveals Lichenicidin Production by Seaweed-Derived Bacillus spp.

by Maria Luz Prieto, Laurie O’Sullivan, Shiau Pin Tan, Peter McLoughlin, Helen Hughes, Paula M. O’Connor, Paul D. Cotter, Peadar G. Lawlor and Gillian E. Gardiner

Mar. Drugs 2012, 10(10), 2280-2299; https://doi.org/10.3390/md10102280 - 19 Oct 2012

Cited by 39 | Viewed by 8583

Abstract

The objectives of this study were (1) to assess the bacteriocinogenic potential of bacteria derived mainly from seaweed, but also sand and seawater, (2) to identify at least some of the bacteriocins produced, if any and (3) to determine if they are unique [...] Read more.

The objectives of this study were (1) to assess the bacteriocinogenic potential of bacteria derived mainly from seaweed, but also sand and seawater, (2) to identify at least some of the bacteriocins produced, if any and (3) to determine if they are unique to the marine environment and/or novel. Fifteen Bacillus licheniformis or pumilus isolates with antimicrobial activity against at least one of the indicator bacteria used were recovered. Some, at least, of the antimicrobials produced were bacteriocins, as they were proteinaceous and the producers displayed immunity. Screening with PCR primers for known Bacillus bacteriocins revealed that three seaweed-derived Bacillus licheniformis harbored the bli04127 gene which encodes one of the peptides of the two-peptide lantibiotic lichenicidin. Production of both lichenicidin peptides was then confirmed by mass spectrometry. This is the first definitive proof of bacteriocin production by seaweed-derived bacteria. The authors acknowledge that the bacteriocin produced has previously been discovered and is not unique to the marine environment. However, the other marine isolates likely produce novel bacteriocins, as none harboured genes for known Bacillus bacteriocins. Full article

(This article belongs to the Special Issue Marine Algae)

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745 KiB

Open AccessArticle

Digital Marine Bioprospecting: Mining New Neurotoxin Drug Candidates from the Transcriptomes of Cold-Water Sea Anemones

by Ilona Urbarova, Bård Ove Karlsen, Siri Okkenhaug, Ole Morten Seternes, Steinar D. Johansen and Åse Emblem

Mar. Drugs 2012, 10(10), 2265-2279; https://doi.org/10.3390/md10102265 - 18 Oct 2012

Cited by 23 | Viewed by 8693

Abstract

Marine bioprospecting is the search for new marine bioactive compounds and large-scale screening in extracts represents the traditional approach. Here, we report an alternative complementary protocol, called digital marine bioprospecting, based on deep sequencing of transcriptomes. We sequenced the transcriptomes from the adult [...] Read more.

Marine bioprospecting is the search for new marine bioactive compounds and large-scale screening in extracts represents the traditional approach. Here, we report an alternative complementary protocol, called digital marine bioprospecting, based on deep sequencing of transcriptomes. We sequenced the transcriptomes from the adult polyp stage of two cold-water sea anemones, Bolocera tuediae and Hormathia digitata. We generated approximately 1.1 million quality-filtered sequencing reads by 454 pyrosequencing, which were assembled into approximately 120,000 contigs and 220,000 single reads. Based on annotation and gene ontology analysis we profiled the expressed mRNA transcripts according to known biological processes. As a proof-of-concept we identified polypeptide toxins with a potential blocking activity on sodium and potassium voltage-gated channels from digital transcriptome libraries. Full article

(This article belongs to the Special Issue Metagenomics in Biodiscovery from Oceans)

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456 KiB

Open AccessArticle

Cytotoxic Activity of Semi-Synthetic Derivatives of Elatol and Isoobtusol

by Karen L. Lang, Izabella T. Silva, Lara A. Zimmermann, Cíntia Lhullier, Maria V. Mañalich Arana, Jorge A. Palermo, Miriam Falkenberg, Cláudia M. O. Simões, Eloir P. Schenkel and Fernando J. Durán

Mar. Drugs 2012, 10(10), 2254-2264; https://doi.org/10.3390/md10102254 - 18 Oct 2012

Cited by 7 | Viewed by 6702

Abstract

In the present study, the in vitro cytotoxic effects of six semi-synthetic derivatives of elatol (1) and isoobtusol (2) were investigated. Chemical modifications were performed on the hydroxyl groups aiming to get derivatives of different polarity, namely the hemisuccinate, [...] Read more.

In the present study, the in vitro cytotoxic effects of six semi-synthetic derivatives of elatol (1) and isoobtusol (2) were investigated. Chemical modifications were performed on the hydroxyl groups aiming to get derivatives of different polarity, namely the hemisuccinate, carbamate and sulfamate. The structural elucidation of the new derivatives was based on detailed NMR and MS spectroscopic analyses. The in vitro cytotoxicity of compounds 1 to 8 was evaluated against A459 and RD tumor cell lines with CC₅₀ values ranging from 4.93 to 41.53 µM. These results suggest that the structural modifications performed on both compounds could be considered a good strategy to obtain more active derivatives. Full article

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395 KiB

Open AccessArticle

Echinohalimane A, a Bioactive Halimane-Type Diterpenoid from a Formosan Gorgonian Echinomuricea sp. (Plexauridae)

by Hsu-Ming Chung, Li-Chung Hu, Wei-Hsuan Yen, Jui-Hsin Su, Mei-Chin Lu, Tsong-Long Hwang, Wei-Hsien Wang and Ping-Jyun Sung

Mar. Drugs 2012, 10(10), 2246-2253; https://doi.org/10.3390/md10102246 - 17 Oct 2012

Cited by 18 | Viewed by 6306

Abstract

A new halimane-type diterpenoid, echinohalimane A (1), was isolated from a gorgonian, identified as Echinomuricea sp. The structure of 1 was determined by spectroscopic methods and this compound was found to exhibit cytotoxicity toward various tumor cells and display an inhibitory [...] Read more.

A new halimane-type diterpenoid, echinohalimane A (1), was isolated from a gorgonian, identified as Echinomuricea sp. The structure of 1 was determined by spectroscopic methods and this compound was found to exhibit cytotoxicity toward various tumor cells and display an inhibitory effect on the release of elastase by human neutrophils. Echinohalimane A (1) is the first halimane analogue from the marine organisms belonging to phylum Cnidaria. Full article

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Open AccessArticle

Biosynthetic Studies on Water-Soluble Derivative 5c (DTX5c)

by Tamara S. Vilches, Manuel Norte, Antonio Hernández Daranas and José J. Fernández

Mar. Drugs 2012, 10(10), 2234-2245; https://doi.org/10.3390/md10102234 - 12 Oct 2012

Cited by 10 | Viewed by 5595

Abstract

The dinoflagellate Prorocentrum belizeanum is responsible for the production of several toxins involved in the red tide phenomenon known as Diarrhetic Shellfish Poisoning (DSP). In this paper we report on the biosynthetic origin of an okadaic acid water-soluble ester derivative, DTX5c, on the [...] Read more.

The dinoflagellate Prorocentrum belizeanum is responsible for the production of several toxins involved in the red tide phenomenon known as Diarrhetic Shellfish Poisoning (DSP). In this paper we report on the biosynthetic origin of an okadaic acid water-soluble ester derivative, DTX5c, on the basis of the spectroscopical analysis of ¹³C enriched samples obtained by addition of labelled sodium [l-¹³C], [2-¹³C] acetate to artificial cultures of this dinoflagellate. Full article

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Open AccessArticle

Anti-Human Rhinoviral Activity of Polybromocatechol Compounds Isolated from the Rhodophyta, Neorhodomela aculeata

by Soon-Hye Park, Jae-Hyoung Song, Taejung Kim, Woon-Seob Shin, Gab Man Park, Seokjoon Lee, Young-Joo Kim, Pilju Choi, Heejin Kim, Hui-Seong Kim, Dur-Han Kwon, Hwa Jung Choi and Jungyeob Ham

Mar. Drugs 2012, 10(10), 2222-2233; https://doi.org/10.3390/md10102222 - 10 Oct 2012

Cited by 20 | Viewed by 6375

Abstract

An extract of the red alga, Neorhodomela aculeata, exhibited antiviral activity against human rhinoviruses. Bioassay-guided purification was performed to yield six compounds, which were subsequently identified as lanosol (1) and five polybromocatechols (2–6) by spectroscopic methods, [...] Read more.

An extract of the red alga, Neorhodomela aculeata, exhibited antiviral activity against human rhinoviruses. Bioassay-guided purification was performed to yield six compounds, which were subsequently identified as lanosol (1) and five polybromocatechols (2–6) by spectroscopic methods, including 1D and 2D NMR and mass spectrometric analyses. Structurally, all of these compounds, except compound 5, contain one or two 2,3-dibromo-4,5-dihydroxyphenyl moieties. In a biological activity assay, compound 1 was found to possess antiviral activity with a 50% inhibitory concentration (IC₅₀) of 2.50 μg/mL against HRV2. Compound 3 showed anti-HRV2 activity, with an IC₅₀ of 7.11 μg/mL, and anti-HRV3 activity, with an IC₅₀ of 4.69 μg/mL, without demonstrable cytotoxicity at a concentration of 20 μg/mL. Collectively, the results suggest that compounds 1 and 3 are candidates for novel therapeutics against two different groups of human rhinovirus. Full article

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Open AccessArticle

Antioxidant and Anti-Protease Activities of Diazepinomicin from the Sponge-Associated Micromonospora Strain RV115

by Usama Ramadan Abdelmohsen, Matthias Szesny, Eman Maher Othman, Tanja Schirmeister, Stephanie Grond, Helga Stopper and Ute Hentschel

Mar. Drugs 2012, 10(10), 2208-2221; https://doi.org/10.3390/md10102208 - 8 Oct 2012

Cited by 63 | Viewed by 8954

Abstract

Diazepinomicin is a dibenzodiazepine alkaloid with an unusual structure among the known microbial metabolites discovered so far. Diazepinomicin was isolated from the marine sponge-associated strain Micromonospora sp. RV115 and was identified by spectroscopic analysis and by comparison to literature data. In addition to [...] Read more.

Diazepinomicin is a dibenzodiazepine alkaloid with an unusual structure among the known microbial metabolites discovered so far. Diazepinomicin was isolated from the marine sponge-associated strain Micromonospora sp. RV115 and was identified by spectroscopic analysis and by comparison to literature data. In addition to its interesting preclinical broad-spectrum antitumor potential, we report here new antioxidant and anti-protease activities for this compound. Using the ferric reducing antioxidant power (FRAP) assay, a strong antioxidant potential of diazepinomicin was demonstrated. Moreover, diazepinomicin showed a significant antioxidant and protective capacity from genomic damage induced by the reactive oxygen species hydrogen peroxide in human kidney (HK-2) and human promyelocytic (HL-60) cell lines. Additionally, diazepinomicin inhibited the proteases rhodesain and cathepsin L at an IC₅₀ of 70–90 µM. It also showed antiparasitic activity against trypomastigote forms of Trypanosoma brucei with an IC₅₀of 13.5 µM. These results showed unprecedented antioxidant and anti-protease activities of diazepinomicin, thus further highlighting its potential as a future drug candidate. Full article

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Open AccessReview

Marine Cyanobacteria Compounds with Anticancer Properties: A Review on the Implication of Apoptosis

by Margarida Costa, João Costa-Rodrigues, Maria Helena Fernandes, Piedade Barros, Vitor Vasconcelos and Rosário Martins

Mar. Drugs 2012, 10(10), 2181-2207; https://doi.org/10.3390/md10102181 - 28 Sep 2012

Cited by 121 | Viewed by 12106

Abstract

Marine cyanobacteria have been considered a rich source of secondary metabolites with potential biotechnological applications, namely in the pharmacological field. Chemically diverse compounds were found to induce cytoxicity, anti-inflammatory and antibacterial activities. The potential of marine cyanobacteria as anticancer agents has however been [...] Read more.

Marine cyanobacteria have been considered a rich source of secondary metabolites with potential biotechnological applications, namely in the pharmacological field. Chemically diverse compounds were found to induce cytoxicity, anti-inflammatory and antibacterial activities. The potential of marine cyanobacteria as anticancer agents has however been the most explored and, besides cytotoxicity in tumor cell lines, several compounds have emerged as templates for the development of new anticancer drugs. The mechanisms implicated in the cytotoxicity of marine cyanobacteria compounds in tumor cell lines are still largely overlooked but several studies point to an implication in apoptosis. This association has been related to several apoptotic indicators such as cell cycle arrest, mitochondrial dysfunctions and oxidative damage, alterations in caspase cascade, alterations in specific proteins levels and alterations in the membrane sodium dynamics. In the present paper a compilation of the described marine cyanobacterial compounds with potential anticancer properties is presented and a review on the implication of apoptosis as the mechanism of cell death is discussed. Full article

(This article belongs to the Special Issue Bioactive Compounds from Marine Microorganisms)

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Open AccessArticle

Sarcophine-Diol Inhibits Expression of COX-2, Inhibits Activity of cPLA₂, Enhances Degradation of PLA₂ and PLC_γ1 and Inhibits Cell Membrane Permeability in Mouse Melanoma B₁₆F₁₀ Cells

by Pawel T. Szymanski, Pratik Muley, Safwat A. Ahmed, Sherief Khalifa and Hesham Fahmy

Mar. Drugs 2012, 10(10), 2166-2180; https://doi.org/10.3390/md10102166 - 28 Sep 2012

Cited by 6 | Viewed by 6136

Abstract

Sarcophine-diol (SD) is a semi-synthetic derivative of sarcophine with a significant chemopreventive effect against non-melanoma skin cancer both in vitro and in vivo. Recently, we have studied the effect of SD on melanoma development using the mouse melanoma B₁₆F₁₀ [...] Read more.

Sarcophine-diol (SD) is a semi-synthetic derivative of sarcophine with a significant chemopreventive effect against non-melanoma skin cancer both in vitro and in vivo. Recently, we have studied the effect of SD on melanoma development using the mouse melanoma B₁₆F₁₀ cell line. In this study, our findings show that SD suppresses cell multiplication and diminishes membrane permeability for ethidium bromide (EB), a model marker used to measure cell permeability for Ca²⁺ ions. SD also decreases protein levels of COX-2, and increases degradation of phospholipasesPLA₂ and PLC_γ1 and diminishes enzymatic activity of the Ca²⁺-dependent cPLA₂. This lower membrane permeability for Ca²⁺-ions, associated with SD, is most likely due to the diminished content of lysophosphosphatidylcholine (lysoPC) within cell membranes caused by the effect of SD on PLA₂. The decrease in diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP₃) due to inhibition of PLC_γ1, leads to the downregulation of Ca²⁺-dependent processes within the cell and also inhibits the formation of tumors. These findings support our previous data suggesting that SD may have significant potential in the treatment of melanoma. Full article

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951 KiB

Open AccessArticle

Sepia Ink Oligopeptide Induces Apoptosis in Prostate Cancer Cell Lines via Caspase-3 Activation and Elevation of Bax/Bcl-2 Ratio

by Fangfang Huang, Zuisu Yang, Di Yu, Jiabin Wang, Rong Li and Guofang Ding

Mar. Drugs 2012, 10(10), 2153-2165; https://doi.org/10.3390/md10102153 - 27 Sep 2012

Cited by 74 | Viewed by 9391

Abstract

Sepia ink oligopeptide (SIO) is a tripeptide extracted from Sepia ink. To test the hypothesis that SIO inhibits prostate cancer by inducing apoptosis, the effects of SIO on the proliferation of three human prostate cancer cell lines were examined using a CCK-8 assay. [...] Read more.

Sepia ink oligopeptide (SIO) is a tripeptide extracted from Sepia ink. To test the hypothesis that SIO inhibits prostate cancer by inducing apoptosis, the effects of SIO on the proliferation of three human prostate cancer cell lines were examined using a CCK-8 assay. SIO significantly inhibited the proliferation of DU-145, PC-3 and LNCaP cells in a time- and dose-dependent manner. Flow cytometry studies showed that exposing DU-145, PC-3 and LNCaP cells to 5, 10, or 15 mg/mL SIO for 24 h increased the percentage of the early-stage apoptotic cells from 11.84% to 38.26% (DU-145), 22.76% to 39.96% (PC-3) and 5.05% to 16.11% (LNCaP), respectively. In addition, typical morphologic changes were observed in the cells with acridine orange/ethidium bromide staining. SIO treatment induced strong S and G₂/M phase cell cycle arrest in a dose-dependent manner in DU-145 and LNCaP. In contrast, SIO treatment induced strong Sub G₁ and G₀/G₁ phase cell cycle arrest in a dose-dependent manner in PC-3. SIO exposure for 24 h decreased the expression of the anti-apoptotic protein Bcl-2 and increased the expression of the apoptogenic protein Bax. Moreover, the Bax/Bcl-2expression ratio was increased. Concurrently, the expression of caspase-3 was upregulated. These data support our hypothesis that SIO has anticarcinogenic properties. Full article

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Open AccessArticle

Structural Analysis of a Heteropolysaccharide from Saccharina japonica by Electrospray Mass Spectrometry in Tandem with Collision-Induced Dissociation Tandem Mass Spectrometry (ESI-CID-MS/MS)

by Weihua Jin, Jing Wang, Sumei Ren, Ni Song and Quanbin Zhang

Mar. Drugs 2012, 10(10), 2138-2152; https://doi.org/10.3390/md10102138 - 25 Sep 2012

Cited by 49 | Viewed by 9459

Abstract

A fucoidan extracted from Saccharina japonica was fractionated by anion exchange chromatography. The most complex fraction F0.5 was degraded by dilute sulphuric acid and then separated by use of an activated carbon column. Fraction Y1 was fractionated by anion exchange and gel filtration [...] Read more.

A fucoidan extracted from Saccharina japonica was fractionated by anion exchange chromatography. The most complex fraction F0.5 was degraded by dilute sulphuric acid and then separated by use of an activated carbon column. Fraction Y1 was fractionated by anion exchange and gel filtration chromatography while Fraction Y2 was fractionated by gel filtration chromatography. The fractions were determined by ESI-MS and analyzed by ESI-CID-MS/MS. It was concluded that F0.5 had a backbone of alternating 4-linked GlcA and 2-linked Man with the first Man residue from the nonreducing end accidentally sulfated at C6. In addition, F0.5 had a 3-linked glucuronan, in accordance with a previous report by NMR. Some other structural characteristics included GlcA 1→3 Man 1→4 GlcA, Man 1→3 GlcA 1→4 GlcA, Fuc 1→4 GlcA and Fuc 1→3 Fuc. Finally, it was shown that fucose was sulfated at C2 or C4 while galactose was sulfated at C2, C4 or C6. Full article

(This article belongs to the Collection Marine Polysaccharides)

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Mar. Drugs, Volume 10, Issue 10 (October 2012) – 16 articles , Pages 2138-2368

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