Hippospongia Sp Research Articles

12-Deacetyl-12-epi-Scalaradial, a Scalarane Sesterterpenoid from a Marine Sponge Hippospongia sp., Induces HeLa Cells Apoptosis via MAPK/ERK Pathway and Modulates Nuclear Receptor Nur77.

12-Deacetyl-12-epi-scalaradial, a scalarane sesterterpenoid from a marine sponge Hippospongia sp, has been reported to possess cytotoxic activity on HepG2, MCF-7, and HCT-116 cells. However, there is no research to indicate that 12-deacetyl-12-epi-scalaradial exhibited anticancer effect on cervical cancer HeLa cells. The aim of this study was to investigate the anticancer activity of 12-deacetyl-12-epi-scalaradial against HeLa cells and to explore the mechanism. The results from a methylthiazolyldiphenyl-tetrazolium (MTT) assay suggested that 12-deacetyl-12-epi-scalaradial suppressed the proliferation of HeLa cells and flow cytometry analysis showed 12-deacetyl-12-epi-scalaradial could induce the apoptosis of HeLa cells in dose- and time-dependent manner. Western blotting analysis demonstrated that 12-deacetyl-12-epi-scalaradial triggered apoptosis via mediating the extrinsic pathway and was found to suppress MAPK/ERK pathway which was associate with cancer cell death. Nur77, a critical number of orphan nuclear receptors, plays diverse roles in tumor development as a transcription factor and has been considered as a promising anticancer drug target. The dual-luciferase reporter assays suggested that 12-deacetyl-12-epi-scalaradial could selectively enhance the trans-activation activity of Nur77. Furthermore, Western blotting analysis and fluorescence quenching showed that 12-deacetyl-12-epi-scalaradial could induce the phosphorylation of Nur77 and interact with the ligand-binding domain (LBD) of Nur77. Our research confirmed 12-deacetyl-12-epi-scalaradial as a potential agent for cervical cancer therapy and provided a view that 12-deacetyl-12-epi-scalaradial may be a modulator of Nur77.

A Norsesterterpene Peroxide from a Marine Sponge Hippospongia sp

One new norsesterterpene peroxide, rhopaloic acid H (1), along with two known related metabolites 2 and 3, were isolated from a marine sponge Hippospongia sp. The structures of compounds were elucidated by means of IR, MS, and NMR techniques and comparison of the NMR data with those of known analogues. Evaluation of the cytotoxicities revealed that compound 2 exhibited significant cytotoxicity against DLD-1, Molt 4, T47D and K-562 cell lines, with IC50 values of 3.18, 0.69, 2.22 and 1.06 µg/mL, respectively. Moreover, compound 3 also showed significant K562 inhibitory activity, with IC50 value of 3.65 µg/mL.

Improvement and enhancement of antibladder carcinoma cell effects of heteronemin by the nanosized hyaluronan aggregation.

The effects against tumors exerted by marine active compounds have been highlighted and investigated. Polymeric nanoparticles made from biodegradable and biocompatible molecules such as hyaluronan (HA) and chitosan (CHI) are able to aggregate the compounds to enhance their activities against tumor cells and reduce the toxicity on normal cells. Here, we extensively examined the antitumor activities and the mechanisms of HA/CHI nanoparticles-aggregated heteronemin (HET) extracted from the sponge Hippospongia sp. The half-maximal inhibitory concentration (IC50) of pure HET toward T24 bladder carcinoma cells is ~0.28 µg/mL. Pure HET from 0.2 to 0.8 µg/mL and HA nanoparticles-aggregated HET at 0.1 and 0.2 µg/mL significantly reduced T24 cell viability. Compared to pure HET, HA nanoparticles/HET aggregates showed much weaker viability-inhibitory effects on L929 normal fibroblasts. HET dose-dependently suppressed cancer cell migration as HA/CHI nanoparticles-aggregated HET displayed stronger migration-inhibitory effects than pure HET. Flow cytometric analysis showed that pure HET increased early/total apoptosis and JC-1 monomer fluorescence, while HA/CHI nanoparticles-aggregated HET induced higher apoptosis and JC-1 monomer rates than pure HET, suggesting that aggregation of HA nanoparticles offers HET stronger apoptosis-inducing capacity through mitochondrial depolarization. Western blot analysis showed that HA nanoparticles-aggregated HET further increased mitochondrial-associated, caspase-dependent and caspase-independent, as well as endoplasmic reticulum stress-related factors in comparison with pure HET. These data indicated that pure HET possesses cytotoxic, antimigratory, and apoptosis-inducing effects on bladder cancer cells in vitro, and its induction of apoptosis in bladder carcinoma cells is mainly caspase dependent. Moreover, HA nanoparticle aggregation reinforced the cytotoxic, antimigratory, and apoptosis-inducing activities against bladder carcinoma cells and attenuated the viability-inhibitory effects on normal fibroblasts. This aggregation reinforces antibladder carcinoma effects of HET via diverse routes, including mitochondrial-related/caspase-dependent, caspase-independent, and endoplasmic reticulum stress-related pathways. The current data also strongly suggested that HA/CHI nanoparticles-aggregated HET would be a potential treatment for urothelial cancer in vivo.

Cytotoxic Scalarane Sesterterpenoids from a Marine Sponge Hippospongia sp

A new scalarane sesterterpenoid, hippospongide C (1), along with four previously reported known scalarane–type sesterterpenes (2–5), were isolated from a sponge Hippospongia sp. The structure of 1 was elucidated on the basis of its spectroscopic data and comparison of its NMR data with those of known analogues. The cytotoxicity of 1–5 against DLD-1, HCT-116, T-47D and K562 cell lines was evaluated. The results showed that compound 4 exhibited potent activity against DLD-1, HCT-116 and T-47D cell lines with IC50 values of 1.3–2.0 μg/mL. Furthermore, metabolites 1–5 were also found to exhibit significant cytotoxicity towards the K562 cell line with IC50 values of 0.01–2.9 μg/mL.

Three bioactive sesquiterpene quinones from the Fijian marine sponge of the genus Hippospongia

A sesquiterpenoid quinone, epi-ilimaquinone (1), and two sesquiterpene amino quinones, smenospongine (2) and glycinylilimaquinone (3), were isolated from the Fijian marine sponge Hippospongia sp. The structures of these compounds were determined by spectroscopic analysis. Compounds 1 and 3 were reported for the first time in this study from the sponge of the genus Hippospongia. Compound 1 displayed potent cytotoxic activity and showed antibacterial activity against methicillin-resistant Staphylococcus aureus, wild type S. aureus and vancomycin-resistant Enterococcus faecium and displayed antifungal activity against amphotericin-resistant Candida albicans while compounds 2 and 3 showed moderate cytotoxic activity. However, compound 1 did not show appreciable antifungal activity against wild type C. albicans, Cryptococcus neoformans, Aspergillus niger, Penicillium sp., Rhizopus sporangia or Sordaria sp.

Cytotoxic Sesterterpenoids from a Sponge Hippospongia sp.

One new pentacyclic sesterterpene, hippospongide A (1), and one new scalarane sesterterpenoid, hippospongide B (2), along with six previously reported known scalarane–type sesterterpenes (3–8), were isolated from a sponge Hippospongia sp. The structures of these compounds were elucidated on the basis of their spectroscopic data and comparison of the NMR data with those of known analogues. These metabolites are the first pentacyclic sesterterpene and scalarane-type sesterterpenes to be reported from this genus. Compounds 3–5 exhibited significant cytotoxicity against DLD-1, HCT-116, T-47D and K562 cancer cell lines.

Synthesis of (-)-Untenospongin C, a C21 Furanoterpene Isolated from the Okinawan Sponge Hippospongia Sp.

The first enantioselective total synthesis of title compound (I) is achieved from (R)-(+)-citronellol through assembly of three fragments.

Promotion of IL-8 production in PMA-stimulated HL-60 cells by sesquiterpene quinones from a marine sponge, Hippospongia sp.

An extract of a marine sponge, Hippospongia sp., collected in Palau has inhibitory activity against colony formation by Chinese hamster V79 cells. Bioassay-guided isolation gave eleven sesquiterpene quinones. Compounds 1–8 inhibited colony formation by V79 cells with EC50 values between 0.6 and 2.8 μmol L−1. Their effects on the production of an inflammatory cytokine, IL-8, in tetradecanoyl phorbol acetate (PMA)-stimulated HL-60 cells were also investigated, because IL-8 production is sometimes correlated with inhibition of cell growth. Ilimaquinone (1) and its 5 epimer (2) had similar activity against V79 cells (EC50 = 2.8 and 2.3 μmol L−1, respectively) but did not modulate IL-8 production even at 10 μmol L−1. Smenospongidine (3) and its 5 epimer (4), smenospongiarine (5) and its 5 epimer (6), and smenospongine (7) and its 5-epimer (8), at 10 μmol L−1, promoted IL-8 production. Compounds 3, 5, and 7 had slightly stronger activity against V79 cells (EC50 = 0.6, 1.7, and 0.8 μmol L−1, respectively) than the corresponding 5 epimers 4, 6, and 8 (EC50 = 0.8, 2.3, and 2.0 μmol L−1, respectively). A similar structure–activity relationship was observed for promotion of IL-8 production. This is the first report of modulation of IL-8 production by these sesquiterpene quinones.

Sesterterpene sulfates as isocitrate lyase inhibitors from tropical sponge Hippospongia sp.

Two sesterterpene sulfates ( 1– 2) were isolated from tropical sponge Hippospongia sp. and their inhibitory activities against isocitrate lyase (ICL) from the rice blast fungus Mgnaporthe grisea were evaluated. Compound 3 was obtained by hydrolysis of compound 1. Compounds 1 and 3 were found to be potent ICL inhibitors, which inhibited appressorium formation and C 2 carbon utilization in M. grisea. Our results suggest that ICL plays crucial role in appressorium formation of M. grisea and is a new target for the protection of rice blast disease.

Associated microbial community of two deep water infected sponge Hippospongia sp. and Cacospongia sp.

The associated microbial community of two infected sponges Hippospongia sp. and Cacospongia sp. were investigated during the summer of 2004 and 2005. The total viable counts associated with Cacospongia sp. exceeds that associated with Hippospongia sp. by 3.6 fold. This bacterial load in the sponge was greater than that of the proximal sea water. Staphylococcus aureus was the predominant species followed by Vibrio parahaemolyticus. It was concluded that sponge samples suffered from large amounts of microbial pathogens, where the infection spread on Cacospongia sp. was greater than that of Hippospongia sp. Moreover, supernatants of seven marine actinomycetes strains were screened for their efficiency to inhibit the growth of the isolated pathogens. The supernatant of Nocardia brasiliensis had the greatest inhibitory effect against Staphylococcus aureus.

Novel sesterterpenoid and norsesterterpenoid RCE-protease inhibitors isolated from the marine sponge Hippospongia sp.

Barangcadoic acid A ( 1 ) and rhopaloic acids D ( 5 ) to G ( 8 ), novel terpenoids with RCE protease inhibitory activity, have been isolated from the marine sponge Hippospongia sp. collected in Indonesia. The structures of 1 and 5– 8 were elucidated by analysis of spectroscopic data.

Synthesis of (R)-(+)-hippospongic acid A, a triterpene isolated from the marine sponge, Hippospongia sp.

Hippospongic acid A (1) is a triterpene metabolite of the marine sponge, Hippospongia sp., with inhibitory activity against the gastrulation of starfish embryos. (R)-(+)-1 was synthesized by employing enzymatic kinetic resolution as the key step.

New Hurghamids from a Red Sea Sponge of the Genus Hippospongia

Three new N-acyl-2-methylene-β-alanine methyl esters, Hurghamides E-G (5–7), were isolated from a Red Sea sponge Hippospongia sp. Their structures were elucidated by extensive spectroscopic studies.

Triterpenoid total synthesis. Part 4.1 Synthesis of (±)-hippospongic acid A, a triterpene isolated from the marine sponge Hippospongia sp.

Hippospongic acid A (1), a triterpene metabolite of a marine sponge Hippospongia sp. with inhibitory activity against gastrulation of starfish embryos, was synthesized as its racemate by starting from (2E,6E)-farnesol (2).

Hurghamides A-D, New N-Acyl-2-Methylene-β-Alanine Methyl Esters from Red Sea Hippospongia Sp

Four new N-acyl-2-methylene-β-alanine methyl esters, named hurghamides A-D (6–9), together with two known analogues 2a and 2b, were isolated from a Red Sea sponge Hippospongia sp. Their structures were elucidated by extensive spectroscopic studies.

Hurghamides A-D, New N-Acyl-2-Methylene-β-Alanine Methyl Esters from Red sea Hippospongia SP

Four new N-acyl-2-methylene-β-alanine methyl esters, named hurghamides A-D (6–9), together with two known analogues 2a and 2b, were isolated from a Red Sea sponge Hippospongia sp. Their structures were elucidated by extensive spectroscopic studies.

Hippospongins A−F: New Furanoterpenes from a Southern Australian Marine Sponge Hippospongia sp.

Three new C25 furanoterpenes, hippospongins A−C (5−7); a new C24 furanoterpene, hippospongin D (8); and two new C22 furanoterpenes, hippospongins E and F (9 and 10), were isolated from a southern Australian collection of the marine sponge Hippospongia sp. The hippospongins possess structural features intermediate between C21 furanoterpenes and their putative biosynthetic precursors, C25 tetronic acids. All structures were secured by detailed spectroscopic analysis.