Purpose: In search for new drugs derived from natural products for the possible treatment of cancer, we studied the action of agelasine B, a compound purified from a marine sponge Agelas clathrodes. ...Methods: Agelasine B was purified from a marine sponge Agelas clathrodes and assayed for cytotoxicity by MTT on two human breast cancer cells (MCF-7 and SKBr3), on a prostate cancer cells (PC-3) and on human fibroblasts. Changes in the intracellular Ca super(2+) concentrations were assessed with FURA 2 and by confocal microscopy. Determination of Ca super(2+)-ATPase activity was followed by Pi measurements. Changes in the mitochondria electrochemical potential was followed with Rhodamine 123. Apoptosis and DNA fragmentation were determined by TUNEL experiments. Results: Upon agelasine B treatment, cell viability of both human breast cancer cell lines was one order of magnitude lower as compared with fibroblasts (IC sub(50) for MCF-7 = 2.99 mu M; SKBr3: IC sub(50) = 3.22 mu M vs. fibroblasts: IC sub(50) = 32.91 mu M) , while the IC sub(50) for PC-3 IC sub(50) = 6.86 mu M. Agelasine B induced a large increase in the intracellular Ca super(2+) concentration in MCF-7, SKBr3, and PC-3 cells. By the use of confocal microscopy coupled to a perfusion system, we could observe that this toxin releases Ca super(2+) from the endoplasmic reticulum (ER). We also demonstrated that agelasine B produces a potent inhibition of the ER Ca super(2+)-ATPase (SERCA), and that this compound induced the fragmentation of DNA. Accordingly, agelasine B reduced the expression of the anti-apoptotic protein Bcl-2 and was able to activate caspase 8, without affecting the activity of caspase 7. Conclusions: Agelasine B in MCF-7 cells induce the activation of apoptosis in response to a sustained increase in the Ca super(2+) sub( i ) after blocking the SERCA activity. The reproduction of the effects of agelasine B on cell viability and on the Ca super(2+) sub( I ) obtained on SKBr3 and PC-3 cancer cells strongly suggests the generality of the mechanism of action of this toxin.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Macroalgal phase shifts on Caribbean reefs have been reported with increasing frequency, and recent reports of these changes on mesophotic coral reefs have raised questions regarding the mechanistic ...processes behind algal population expansions to deeper depths. The brown alga Lobophora variegata is a dominant species on many shallow and deep coral reefs of the Caribbean and Pacific, and it increased in percent cover (>50%) up to 61 m on Bahamian reefs following the invasion of the lionfish Pterois volitans. We examined the physiological and ecological constraints contributing to the spread of Lobophora on Bahamian reefs across a mesophotic depth gradient from 30 to 61 m, pre‐ and post‐lionfish invasion. Results indicate that there were no physiological limitations to the depth distribution of Lobophora within this range prior to the lionfish invasion. Herbivory by acanthurids and scarids in algal recruitment plots at mesophotic depths was higher prior to the lionfish invasion, and Lobophora chemical defenses were ineffective against an omnivorous fish species. In contrast, Lobophora exhibited significant allelopathic activity against the coral Montastraea cavernosa and the sponge Agelas clathrodes in laboratory assays. These data indicate that when lionfish predation on herbivorous fish released Lobophora from grazing pressure at depth, Lobophora expanded its benthic cover to a depth of 61 m, where it replaced the dominant coral and sponge species. Our results suggest that this chemically defended alga may out‐compete these species in situ, and that mesophotic reefs may be further impacted in the near future as Lobophora continues to expand to its compensation point.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Although marine sponges are known for their antimicrobial, antifungal and cytotoxic activity, very few studies have been carried out on endemic species of Martinique. Martinique is part of the Agoa ...Sanctuary, a marine protected area that includes the exclusive economic zones (EEZ) of the French Caribbean islands, making it an abundant source of marine species. To highlight the potential of this area for the discovery of marine biomolecules with antipathogenic and antitumor activities, we tested the aqueous and ethanolic extracts of sponge species
,
and
. Five bacterial strains:
(CIP 78.3),
(CIP 54.127),
(CIP A22),
(CIP 67.8) and
(CIP 76125) were evaluated, as well as four tumor cell lines: breast cancer (MDA-MB231), glioblastoma (RES259) and leukemia (MOLM14 and HL-60). Antimicrobial activity was evaluated using the disc diffusion technique by determining the minimum inhibitory and minimum bactericidal concentrations. Tumor cytotoxic activity was determined
by defining the minimum concentration of extracts that would inhibit cell growth. Ethanolic extracts of
were bactericidal for
and
strains, as well as strongly cytotoxic (IC
< 20 µg/mL) on all cancer cell lines.
also showed strong cytotoxic activity on cell lines but no antimicrobial activity. These results are innovative for this species on these bacterial lines, highlighting the potential of sponge extracts from this area as bioactive compounds sources.
Two families of unique glycolipids, clathrosides A-C (2a-4a) and isoclathrosides A-C (5a-7a) were isolated from the Caribbean sponge Agelas clathrodes. Clathrosides and isoclathrosides are glycosides ...of a very-long-chain alcohol derived from fatty acids, a new class of glycolipids that appears to be characteristic of marine sponges. The six compounds differ in configuration and in the branching of alkyl chains. Stereostructures of the clathrosides were determined by NMR and CD spectroscopy, mass spectrometry, and chemical degradation. Location of the methyl branch on the proper alkyl chain required an exceptional 1-D TOCSY experiment in which coherence was transferred through as many as 13 vicinal couplings.
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Filled circles represent seawater column sample collection sites; filled squares represent Buoy 2 and Buoy 4 (sponge, seawater column, and near reef seawater collection) and open circle represents ...location of TABS Buoy V (surface salinity data collection); (B) representative Xestospongia muta sponge; (C) representative Agelas clathrodes sponge; (D) surface Salinity (ppt) at buoy V spanning the months April through October in which sampling occurred for this study. Empty symbols = samples collected from East Bank (EB); filled symbols = samples collected from West Bank (WB) of the Flower Garden Banks National Marine Sanctuary (northern Gulf of Mexico). Amanda Shore1,2*, Jordan A. Sims1, Michael Grimes3, Lauren I. Howe-Kerr1, Carsten G. B. Grupstra1, Shawn M. Doyle4, Lauren Stadler5, Jason B. Sylvan4, Kathryn E. F. Shamberger4, Sarah W. Davies6, Lory Z. Santiago-Vázquez3 and Adrienne M. S. Correa1 * 1Department of BioSciences, Rice University, Houston, TX, United States * 2Department of Biology, Farmingdale State College, Farmingdale, NY, United States * 3Department of Biology and Biotechnology, University of Houston-Clear Lake, Clear Lake, TX, United States * 4Deparment of Oceanography, Texas A&M University, College Station, TX, United States * 5Civil and Environmental Engineering, Rice University, Houston, TX, United States * 6Department of Biology, Boston University, Boston, MA, United States
Terrestrial runoff can negatively impact marine ecosystems through stressors including excess nutrients, freshwater, sediments, and contaminants. Severe storms, which are increasing with global ...climate change, generate massive inputs of runoff over short timescales (hours to days); such runoff impacted offshore reefs in the northwest Gulf of Mexico (NW GoM) following severe storms in 2016 and 2017. Several weeks after coastal flooding from these events, NW GoM reef corals, sponges, and other benthic invertebrates ∼185 km offshore experienced mortality (2016 only) and/or sub-lethal stress (both years). To assess the impact of storm-derived runoff on reef filter feeders, we characterized the bacterial communities of two sponges,
Agelas clathrodes
and
Xestospongia muta
, from offshore reefs during periods of sub-lethal stress and no stress over a three-year period (2016—2018). Sponge-associated and seawater-associated bacterial communities were altered during both flood years. Additionally, we found evidence of wastewater contamination (based on 16S rRNA gene libraries and quantitative PCR) in offshore sponge samples, but not in seawater samples, following these flood years. Signs of wastewater contamination were absent during the no-flood year. We show that flood events from severe storms have the capacity to reach offshore reef ecosystems and impact resident benthic organisms. Such impacts are most readily detected if baseline data on organismal physiology and associated microbiome composition are available. This highlights the need for molecular and microbial time series of benthic organisms in near- and offshore reef ecosystems, and the continued mitigation of stormwater runoff and climate change impacts.
Chemical and physical defenses of sessile organisms against consumers are well described for both terrestrial and marine systems. However, previous studies have focused on chemical or physical ...defenses in isolation, and have not considered their interaction. Marine sponges provide a model system for testing this interaction. Some sponge species produce secondary metabolites that deter predation; they may also contain siliceous spicules, but previous studies have provided little evidence that spicules in isolation offer any defense against generalist fish predators. To determine whether the two components have an additive, antagonistic, or synergistic interaction, crude organic extracts and spicules from individuals of 8 Caribbean sponge species were isolated and tested in laboratory feeding assays. These included one chemically defended reef sponge (
Agelas clathrodes) and seven known to be intermediately deterrent: six from reef habitats (
Cinachyrella alloclada,
Clathria virgultosa,
Cribrochalina infundibulum,
Niphates digitalis,
Svenzea zeai, and
Xestospongia muta) and one from mangrove habitats (
Tedania ignis). Extracts and spicules were assayed at various concentrations, both individually and in combination, in laboratory feeding assays with the bluehead wrasse,
Thalassoma bifasciatum. A SAS based GENMOD procedure based on an isobolographic analysis model was used for statistical comparisons. Four sponges (
A. clathrodes,
C. alloclada,
C. virgultosa, and one of three individuals of
X. muta) showed evidence of synergisms. Of these, synergy in
C. alloclada,
C. virgultosa, and
X. muta was caused by approximately natural concentrations of extracts and spicules. The extract of
A.
clathrodes was deterrent, but combination assays required nearly a 3-fold reduction in extract concentration and an 8-fold increase in spicule concentration to show the synergistic effect. Contrary to previous findings, spicules from
C. infundibulum and two of three individuals of
X. muta were deterrent at natural concentrations. Sponge spicules may be defensive in isolation, or may enhance chemical defenses against consumers, but the lack of synergisms for individuals in 4 of 7 species with intermediate levels of chemical defense suggests that defensive synergy is not the general rule and, when present, may be an example of an exaptation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Reinvestigation of the glycosphingolipid composition of the marine sponge Agelas clathrodes revealed the presence of a new tetraglycosylated alpha-galactoglycosphingolipid (1a), containing an unusual ...l-rhamnose unit in the sugar head. The structure of the new compound was elucidated using extensive 2D NMR studies. Because of the strong overlapping of the signals of the sugar protons in the (1)H spectrum, (13)C-coupled and (13)C-decoupled phase-sensitive HMQC spectra were used to study the multiplicity of the overlapping signals. In addition, the absolute configuration of sugars was determined using a simple and efficient, yet underutilized CD method.
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A new bisuracil analogue, 3,3-bis(uracil-1-yl)-propan-1-aminium (1), together with four known N-containing metabolites (2–5), were isolated from the South China Sea sponge Agelas clathrodes. Their ...chemical structures were established on the basis of spectroscopic and spectrometric analysis and comparison with known compounds. Compound 1 is an unusual naturally occurring bisuracil analogue, and compound 2 was isolated from a natural source for the first time. Compounds 2 and 4 exhibit moderate cytotoxicity against cancer cell line SGC7901.
Previous studies have determined that Caribbean reef sponges of the genus Agelas are chemically defended from fish predation by brominated pyrrole alkaloids, and that the compounds responsible for ...this defense have been elucidated for 1 species, A. clathrodes. In this study, we expand our understanding of chemical defense in this common sponge genus to include the characterization of defensive metabolites in the tissues of A. wiedenmayeri and A. conifera. Bioassay-directed isolation of defensive metabolites was undertaken using fish feeding assays carried out in laboratory aquaria and in the field. A. wiedenmayeri contained the same 2 major metabolites as A. clathrodes, 4,5-dibromopyrrole-2-carboxylic acid (1), and oroidin (2), in addition to a small amount of bromoageliferin (7). The 2 major metabolites were present at higher concentrations in samples of A. wiedenmayeri than in A. clathrodes, and their relative concentrations were reversed, with A. wiedenmayeri on average containing more 4,5-dibromopyrrole-2-carboxylic acid (1) (2.0 mg ml super(-1)) than oroidin (2) (0.8 mg ml super(-1)). A. conifera contained a mixture of dimeric bromopyrrole alkaloids dominated by sceptrin (3), with <10% each of dibromosceptrin (5), bromoageliferin (7), dibromoageliferin (8), ageliferin (6), and bromosceptrin (4). Mean concentration of sceptrin (3) in sponge tissue was 5.3 mg ml super(-1); this compound deterred feeding of reef fish in aquarium assays at 1.0 mg ml super(-1), the lowest concentration assayed. Sceptrin (3) concentrations were higher in sponges collected in the southern Bahama Islands than in those collected in the middle Bahamas, but the reasons for this variation remain unclear. The structure-activity relationship of the pyrrole group was investigated by assaying derivatives of the active metabolites. Feeding deterrent activity of the molecule was enhanced by the addition of bromine to the pyrrole group, but not affected by exchange of the heteroatom from N to O or S. Combining an understanding of the structure-activity relationship of Agelas metabolites with an understanding of the variation in these metabolites across the genus may provide insight into the evolution of defensive chemistry in this highly successful taxa of pan-tropical sponges.
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