Lectins as a promising therapeutic agent for breast cancer: A review.

Efficient treatment of cancer has been a subject of research by scientists for many years. Current treatments for cancer, such as radiotherapy, chemotherapy and surgery have been used in traditional combination therapy, but they have major setbacks like non-specificity, non-responsiveness in certain cancer types towards treatment, tumor recurrence, etc. Epidemiological data has shown that breast cancer accounts for 14% of cancer cases occurring in Indian women. In recent years, scientists have started to focus on the use of natural compounds like lectins obtained from various sources to counter the side effects of traditional therapy. Lectins like Sambucus nigra Agglutinin, Maackia amurensis lectin, Okra lectins, Haliclona caerulea lectin, Sclerotium rolfsii lectin, etc., have been discovered to have both diagnostic and therapeutic potential for breast cancer patients. Lectins have been found to have inhibitory effects on various cancer cell activities such as neo-angiogenesis, causing cell cycle arrest at the G1 phase, and inducing apoptosis. The major idea behind the use of lectins in cancer diagnostics and therapeutics is their capability to bind to glycosylated proteins that are expressed on the cell surface. This review focuses on an exploration of the roles of post-translational modification in cancer cells, especially glycosylation, and the potential of lectins in cancer diagnosis and therapeutics.

Chemical and microbiological insights into two littoral Antarctic demosponge species: Haliclona (Rhizoniera) dancoi (Topsent 1901) and Haliclona (Rhizoniera) scotti (Kirkpatrick 1907).

Introduction: Antarctic Porifera have gained increasing interest as hosts of diversified associated microbial communities that could provide interesting insights on the holobiome system and its relation with environmental parameters. Methods: The Antarctic demosponge species Haliclona dancoi and Haliclona scotti were targeted for the determination of persistent organic pollutant (i. e., polychlorobiphenyls, PCBs, and polycyclic aromatic hydrocarbons, PAHs) and trace metal concentrations, along with the characterization of the associated prokaryotic communities by the 16S rRNA next generation sequencing, to evaluate possible relationships between pollutant accumulation (e.g., as a stress factor) and prokaryotic community composition in Antarctic sponges. To the best of our knowledge, this approach has been never applied before. Results: Notably, both chemical and microbiological data on H. scotti (a quite rare species in the Ross Sea) are here reported for the first time, as well as the determination of PAHs in Antarctic Porifera. Both sponge species generally contained higher amounts of pollutants than the surrounding sediment and seawater, thus demonstrating their accumulation capability. The structure of the associated prokaryotic communities, even if differing at order and genus levels between the two sponge species, was dominated by Proteobacteria and Bacteroidota (with Archaea abundances that were negligible) and appeared in sharp contrast to communities inhabiting the bulk environment. Discussions: Results suggested that some bacterial groups associated with H. dancoi and H. scotti were significantly (positively or negatively) correlated to the occurrence of certain contaminants.

A new amide from the marine sponge Haliclona baeri.

A new amide, baeriamide (1), along with nine known diketopiperazines (2-10), was isolated from the marine sponge Haliclona baeri. Their structures were identified by the means of UV, IR, MS and NMR. The absolute configuration of 1 was established by Marfey's method and comparing the specific optical rotation with the known compound HCO-Val-Gly methyl ester. Compound 1 was derived from dehydration of formylated L-valine with γ-amino-butanoic acid methyl ester. Compounds 2-10 were isolated from the genus of Haliclona for the first time. The absolute confirmation of 7 was confirmed first by the means of single-crystal X-ray diffraction. The cytotoxic, antibacterial, antiviral and antifouling activities of these compounds were also tested. However, none of them exhibited significant bioactivities.

Antifungal and antibacterial activity of marine sponges from Ratnagiri coast of India.

Marine sponges have proved to be a rich source of bioactive metabolites with multiple pharmacological properties. In this study, we have investigated the antifungal and antibacterial activities of methanol extracts of Cliona, Haliclona cratera, Hyrtios cavernosus, Spongia obscura, Sarcotragus foetidus, and Xestospongia carbonaria and fractions from X. carbonaria S. obscura and H. cratera. The antibacterial activity was determined by agar disc diffusion method against clinical gram-positive- Staphylococcus aureus, Bacillus subtilis and gram negative- Escherichia coli, Pseudomonas aeruginosa bacteria. The antifungal activity of the extracts and fractions was determined against Candida albicans and Aspergillus niger. S. obscura, X. carbonaria, H. cavernosus, and H. cratera exhibited good antibacterial activity against the tested gram-positive bacteria with larger zones of inhibition at 19±6 mm, 19.5±5.5mm, 20±0 mm and 23±0 mm. S. foetidus gave good inhibition of gram-negative bacteria at 19±0 mm. They showed moderate antifungal activities against C. albicans and A. niger. Cliona, H. cratera and H. cavernosus gave inhibition with 20±5 mm, 15.5±0.5 mm and 25.5±14.5 mm for A. niger. The MIC for Xc_PE_2, Sob_n but_1 and Hc_n but_3 was determined. H. cavernosus, S. foetidus, S. obscura and X. carbonaria showed presence of fatty acids and sterol type of compounds. The mass of molecular ions in purified fractions helped in characterization of known compounds in H. cratera, X. carbonaria and S. obscura which exhibited good antimicrobial activity.

First certain record of Demospongiae class (Porifera) alien species from the Mediterranean Sea.

In this paper, we identify some sponge specimens collected in the Faro Lake in Sicily, and belonging to Haliclona (Halicoclona) by using morphological analysis accompanied by molecular analysis through amplification of several molecular markers (18S and 28S rRNA, CO1 and ITS). The samples are identified as. H. (Halichoclona) vansoesti de Weerdt, de Kluijver & Gómez, 1999, a species native to the Caribbean, and therefore this is the first record of an alien species of the Demospongiae class (Porifera) from the Mediterranean Sea. This presence can be ascribed as results of global change (mainly global warming) that are affecting marine environment.

Actinoporin-like Proteins Are Widely Distributed in the Phylum Porifera.

Actinoporins are proteinaceous toxins known for their ability to bind to and create pores in cellular membranes. This quality has generated interest in their potential use as new tools, such as therapeutic immunotoxins. Isolated historically from sea anemones, genes encoding for similar actinoporin-like proteins have since been found in a small number of other animal phyla. Sequencing and de novo assembly of Irish Haliclona transcriptomes indicated that sponges also possess similar genes. An exhaustive analysis of publicly available sequencing data from other sponges showed that this is a potentially widespread feature of the Porifera. While many sponge proteins possess a sequence similarity of 27.70-59.06% to actinoporins, they show consistency in predicted structure. One gene copy from H. indistincta has significant sequence similarity to sea anemone actinoporins and possesses conserved residues associated with the fundamental roles of sphingomyelin recognition, membrane attachment, oligomerization, and pore formation, indicating that it may be an actinoporin. Phylogenetic analyses indicate frequent gene duplication, no distinct clade for sponge-derived proteins, and a stronger signal towards actinoporins than similar proteins from other phyla. Overall, this study provides evidence that a diverse array of Porifera represents a novel source of actinoporin-like proteins which may have biotechnological and pharmaceutical applications.

Densazalin, a New Cytotoxic Diazatricyclic Alkaloid from the Marine Sponge Haliclona densaspicula.

Densazalin, a polycyclic alkaloid, was isolated from the marine sponge Haliclona densaspicula collected in Korea. The complete structure of the compound was determined by spectroscopic methods, including 1D and 2D nuclear magnetic resonance techniques, high-resolution mass spectrometry, and comparison of the calculated and measured electronic circular dichroism spectra. Densazalin possesses a unique 5,11-diazatricyclo[7.3.1.02,7]tridecan-2,4,6-triene moiety, which is connected by two linear carbon chains. This compound was derived from the biogenetic precursor bis-1,3-dialkylpyridnium. Densazalin exhibited cytotoxic activity on two human tumor cell lines (AGS and HepG2) in the Cell Counting Kit-8 (CCK-8) bioassay, with IC50 values ranging from 15.5 to 18.4 µM.

Natural Products from the Marine Sponge Subgenus Reniera.

Marine sponges are one of the prolific producers of bioactive natural products with therapeutic potential. As an important subgenus of Haliclona, Reniera sponges are mainly distributed in the Mediterranean Sea and Atlantic area, and had been chemically investigated for over four decades. By an extensive literature search, this review first makes a comprehensive summary of all natural products from Reniera sponges and their endozoic microbes, as well as biological properties. Perspectives on strengthening the chemical study of Reniera sponges for new drug-lead discovery are provided in this work.

Isoquinolinequinone Derivatives from a Marine Sponge (Haliclona sp.) Regulate Inflammation in In Vitro System of Intestine.

Using bio-guided fractionation and based on the inhibitory activities of nitric oxide (NO) and prostaglandin E2 (PGE2), eight isoquinolinequinone derivatives (1-8) were isolated from the marine sponge Haliclona sp. Among these, methyl O-demethylrenierate (1) is a noble ester, whereas compounds 2 and 3 are new O-demethyl derivatives of known isoquinolinequinones. Compound 8 was assigned as a new 21-dehydroxyrenieramycin F. Anti-inflammatory activities of the isolated compounds were tested in a co-culture system of human epithelial Caco-2 and THP-1 macrophages. The isolated derivatives showed variable activities. O-demethyl renierone (5) showed the highest activity, while 3 and 7 showed moderate activities. These bioactive isoquinolinequinones inhibited lipopolysaccharide and interferon gamma-induced production of NO and PGE2. Expression of inducible nitric oxide synthase, cyclooxygenase-2, and the phosphorylation of MAPKs were down-regulated in response to the inhibition of NF-κB nuclear translocation. In addition, nuclear translocation was markedly promoted with a subsequent increase in the expression of HO-1. Structure-activity relationship studies showed that the hydroxyl group in 3 and 5, and the N-formyl group in 7 may be key functional groups responsible for their anti-inflammatory activities. These findings suggest the potential use of Haliclona sp. and its metabolites as pharmaceuticals treating inflammation-related diseases including inflammatory bowel disease.

Identification bacteria associated with Haliclona sp. sponges from Enggano Island, Indonesia with antimicrobial activity against human pathogens

Aims@#Antimicrobial compounds are bioactive compounds that have ability to inhibit microbial growth activities. This study aimed to screen and identify bacteria associated with Haliclona sp. sponges from Enggano Island, Indonesia that had potential to produce antimicrobial compounds against Escherichia coli, Candida albicans and Staphylococcus epidermidis.@*Methodology and results@#The method used to screen and identify bacteria in this study including screening assay, morphological identification, Gram staining and spore staining method, biochemical tests and molecular identification based on 16S rRNA gene. This study resulted 16 isolates which were successfully isolated from Haliclona sp. According to screening assay, 5 isolates could potentially produce antimicrobial compounds coded as HEBS1, HEBS3, HEBS6, HEBB2 and HEBB3. Based on Gram staining, spore staining, biochemical test and molecular identification results, HEBS1 had proximity to Brachybacterium paraconglomeratum, HEBS3 had proximity to Kocuria palustris, HEBS6 had proximity to Psychrobacter pasificensis, HEBB2 had proximity to Bacillus aryabhattai, and HEBB3 had proximity to Bacillus toyonensis.@*Conclusion, significance and impact of study@#From 16 isolates that successfully isolated, there were 5 isolates that could potentially produce antimicrobial compounds against Escherichia coli, Staphylococcus epidermidis and Candida albicans. These isolates can be served as antimicrobial compounds producer. However, identification and purification of these antimicrobial compounds are needed to be done before applied it for medicine in the future.

Gracilosulfates A-G, Monosulfated Polyoxygenated Steroids from the Marine Sponge Haliclona gracilis.

Seven new polyoxygenated steroids belonging to a new structural group of sponge steroids, gracilosulfates A-G (1-7), possessing 3ß-O-sulfonato, 5ß,6ß epoxy (or 5(6)-dehydro), and 4ß,23-dihydroxy substitution patterns as a common structural motif, were isolated from the marine sponge Haliclona gracilis. Their structures were determined by NMR and MS methods. The compounds 1, 2, 4, 6, and 7 inhibited the expression of prostate-specific antigen (PSA) in 22Rv1 tumor cells.

Osirisynes G-I, New Long-Chain Highly Oxygenated Polyacetylenes from the Mayotte Marine Sponge Haliclona sp.

Chemical study of the CH2Cl2-MeOH (1:1) extract from the sponge Haliclona sp. collected in Mayotte highlighted three new long-chain highly oxygenated polyacetylenes, osirisynes G-I (1-3) together with the known osirisynes A (4), B (5), and E (6). Their structures were elucidated by 1D and 2D NMR spectra and HRESIMS and MS/MS data. All compounds were evaluated on catalase and sirtuin 1 activation and on CDK7, proteasome, Fyn kinase, tyrosinase, and elastase inhibition. Five compounds (1; 3-6) inhibited proteasome kinase and two compounds (5-6) inhibited CDK7 and Fyn kinase. Osirisyne B (5) was the most active compound with IC50 on FYNB kinase, CDK7 kinase, and proteasome inhibition of 18.44 µM, 9.13 µM, and 0.26 µM, respectively.

Bioactive Nitrogenous Secondary Metabolites from the Marine Sponge Genus Haliclona.

Marine sponge genus Haliclona, one of the most prolific sources of natural products, contains over 600 species but only a small part of them had been classified and chemically investigated. On the basis of extensive literature search, this review firstly summarizes 112 nitrogenous secondary metabolites from classified and unclassified Haliclona sponges as well as from their symbiotic microorganisms. Most of these substances have only been found in Haliclona sponges, and display diverse bioactive properties with potential applications in new drug discovery.

New sponge species from hydrothermal vent and cold seep sites off New Zealand.

Three new sponge species in the demosponge families Chalinidae Gray and Suberitidae Schmidt are described from the Calypso hydrothermal vent field in the Bay of Plenty, and one species from seep sites along the Hikurangi Margin, to the east of the North Island, New Zealand. The Calypso hydrothermal vent field is dominated by the chalinid sponge Haliclona (Soestella) battershilli sp. nov., a large, cream-coloured, finely branched species, and the less common H. (Halichoclona) sonnae sp. nov., an encrusting, translucent white, cushion-shaped species. The third species, the suberitid sponge Protosuberites novaezelandiae sp. nov., forms encrustations with digitate projections. Haliclona (Halichoclona) sonnae sp. nov. and Protosuberites novaezelandiae sp. nov. represent new subgenus and genus records, respectively, for New Zealand waters. The methanotrophic suberitid sponge, Pseudosuberites thurberi sp. nov., is found at many of the cold seep sites on the Hikurangi Margin where it forms extensive, encrusting to digitate mats. The description of these species provides a basis for the future study of the ecology of sponges that are apparently endemic to vent and seep habitats off New Zealand.

Identification of Fromiamycalin and Halaminol A from Australian Marine Sponge Extracts with Anthelmintic Activity against Haemonchus contortus.

There is an urgent need to discover and develop new anthelmintics for the treatment of parasitic nematodes of veterinary importance to circumvent challenges linked to drug resistant parasites. Being one of the most diverse natural ecosystems, the marine environment represents a rich resource of novel chemical entities. This study investigated 2000 extracts from marine invertebrates, collected from Australian waters, for anthelmintic activity. Using a well-established in vitro bioassay, these extracts were screened for nematocidal activity against Haemonchus contortus-a socioeconomically important parasitic nematode of livestock animals. Extracts (designated Mu-1, Ha-1 and Ha-2) from two marine sponges (Monanchora unguiculata and Haliclona sp.) each significantly affected larvae of H. contortus. Individual extracts displayed a dose-dependent inhibition of both the motility of exsheathed third-stage larvae (xL3s) and the development of xL3s to fourth-stage larvae (L4s). Active fractions in each of the three extracts were identified using bioassay-guided fractionation. From the active fractions from Monanchora unguiculata, a known pentacyclic guanidine alkaloid, fromiamycalin (1), was purified. This alkaloid was shown to be a moderately potent inhibitor of L4 development (half-maximum inhibitory concentration (IC50) = 26.6 ± 0.74 µM) and L4 motility (IC50 = 39.4 ± 4.83 µM), although it had a relatively low potency at inhibiting of xL3 motility (IC50 ≥ 100 µM). Investigation of the active fractions from the two Haliclona collections led to identification of a mixture of amino alcohol lipids, and, subsequently, a known natural product halaminol A (5). Anthelmintic profiling showed that 5 had limited potency at inhibiting larval development and motility. These data indicate that fromiamycalin, other related pentacyclic guanidine alkaloids and/or halaminols could have potential as anthelmintics following future medicinal chemistry efforts.

Biomimetic Approaches for the Development of New Antifouling Solutions: Study of Incorporation of Macroalgae and Sponge Extracts for the Development of New Environmentally-Friendly Coatings.

Biofouling causes major economic losses in the maritime industry. In our site study, the Bay of La Paz (Gulf of California), biofouling on immersed structures is a major problem and is treated mostly with copper-based antifouling paints. Due to the known environmental effect of such treatments, the search for environmentally friendly alternatives in this zone of high biodiversity is a priority to ensure the conservation and protection of species. The aim of this work was to link chemical ecology to marine biotechnology: indeed, the natural defense of macroalgae and sponge was evaluated against biofoulers (biofilm and macrofoulers) from the same geographical zone, and some coatings formulation was done for field assays. Our approach combines in vitro and field bioassays to ensure the selection of the best AF agent prospects. The 1st step consisted of the selection of macroalgae (5 species) and sponges (2 species) with surfaces harboring a low level of colonizers; then extracts were prepared and assayed for toxicity against Artemia, activity towards key marine bacteria involved in biofilm formation in the Bay of La Paz, and the potency to inhibit adhesion of macroorganisms (phenoloxidase assays). The most active and non-toxic extracts were further studied for biofouling activity in the adhesion of the bacteria involved in biofilm formation and through incorporation in marine coatings which were immersed in La Paz Bay during 40 days. In vitro assays demonstrated that extracts of Laurencia gardneri, Sargassum horridum (macroalgae), Haliclona caerulea and Ircinia sp. (sponges) were the most promising. The field test results were of high interest as the best formulation were composed of extracts of H. caerulea and S. horridum and led to a reduction of 32% of biofouling compared with the control.

Haloferax sulfurifontis GUMFAZ2 producing xylanase-free cellulase retrieved from Haliclona sp. inhabiting rocky shore of Anjuna, Goa-India.

Salt stable cellulases are implicated in detritic food webs of marine invertebrates for their role in the degradation of cellulosic material. A haloarchaeon, Haloferax sulfurifontis GUMFAZ2 producing cellulase was successfully isolated from marine Haliclona sp., a sponge inhabiting the rocky intertidal region of Anjuna, Goa. The culture produced extracellular xylanase-free cellulase with a maximum activity of 11.7 U/ml, using carboxymethylcellulose-Na (CMC-Na), as a sole source of carbon in 3.5 M NaCl containing medium, pH 7 at 40°C and produced cellobiose and glucose, detectable by thin-layer chromatography. Nondenaturing polyacrylamide gel electrophoresis of the crude enzyme, revealed a single protein band of 19.6 kDa which on zymographic analysis exhibited cellulase activity while corresponding sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed a molecular weight of 46 kDa. Unlike conventional cellulases, this enzyme is active in presence of 5 M NaCl and does not have accompanying xylanase activity, hence can be considered as xylanase-free cellulase. Such enzymes from haloarchaea offer great potential for biotechnological application because of their stability at high salinity and is therefore worth pursuing.

Silicatein expression in Haliclona indistincta (Phylum Porifera, Order Haplosclerida) at different developmental stages.

Silicatein is the main protein responsible for the formation of spicules, tiny structures that constitute the silica skeleton of marine demosponges (Phylum Porifera). A unique innovation in Porifera that evolved from the cathepsin L family of proteins, it has been reported that two amino acids (S and H) are necessary to form the catalytic triad (SHN) to enable silica condensation. However, a diversity of silicatein sequence variants has since been reported with a variable pattern of presence/absence across sponge groups. Variants containing CHN or C/SQN at the active site appear more common in sponges from the Haplosclerida. Here, we report the expression levels of five silicatein variants through different developmental stages in the haplosclerid Haliclona indistincta. All five silicatein variants were expressed at low levels in the free-swimming larvae, which lack spicules and expression significantly increased at the two developmental phases in which spicules were visible. At these two phases, silicateins of CHN and C/SQN types were much more highly expressed than the SHN type indicating a possible ability of active sites with these alternative amino acids to condense silica and a more complex evolutionary story for spicule formation in marine demosponges than previously understood.

Stable and Enriched Cenarchaeum symbiosum and Uncultured Betaproteobacteria HF1 in the Microbiome of the Mediterranean Sponge Haliclona fulva (Demospongiae: Haplosclerida).

Sponges harbor characteristic microbiomes derived from symbiotic relationships shaping their lifestyle and survival. Haliclona fulva is encrusting marine sponge species dwelling in coralligenous accretions or semidark caves of the Mediterranean Sea and the near Atlantic Ocean. In this work, we characterized the abundance and core microbial community composition found in specimens of H. fulva by means of electron microscopy and 16S amplicon Illumina sequencing. We provide evidence of its low microbial abundance (LMA) nature. We found that the H. fulva core microbiome is dominated by sequences belonging to the orders Nitrosomonadales and Cenarchaeales. Seventy percent of the reads assigned to these phylotypes grouped in a very small number of high-frequency operational taxonomic units, representing niche-specific species Cenarchaeum symbiosum and uncultured Betaproteobacteria HF1, a new eubacterial ribotype variant found in H. fulva. The microbial composition of H. fulva is quite distinct from those reported in sponge species of the same Haliclona genus. We also detected evidence of an excretion/capturing loop between these abundant microorganisms and planktonic microbes by analyzing shifts in seawater planktonic microbial content exposed to healthy sponge specimens maintained in aquaria. Our results suggest that horizontal transmission is very likely the main mechanism for symbionts' acquisition by H. fulva. So far, this is the first shallow water sponge species harboring such a specific and predominant assemblage composed of these eubacterial and archaeal ribotypes. Our data suggests that this symbiotic relationship is very stable over time, indicating that the identified core microbial symbionts may play key roles in the holobiont functioning.

Halilectin-3, a Lectin from the Marine Sponge Haliclona caerulea, Induces Apoptosis and Autophagy in Human Breast Cancer MCF7 Cells Through Caspase-9 Pathway and LC3-II Protein Expression.

BACKGROUND: An ideal strategy for cancer treatment is the specific induction of tumor cell death, sparing normal cells. Marine sponges are rich biological reservoirs of biomolecules, especially lectins, which have attracted considerable attention due to potential biological effect on human cells. Lectins are proteins that bind specific carbohydrate signatures and some gained further interest for their capacity to bind tumor associated carbohydrates antigens and induce tumor cell apoptosis. OBJECTIVE: This study aimed to evaluate the antitumor potential of H3, a lectin, recently reported from marine sponge Haliclona caerulea on the human breast cancer cell line MCF7. RESULTS: H3 reduced MCF7 cell viability with an IC50 of 100 µg/ml, without a significant effect on normal cells. At 24 h, H3 induced a significant arrest in the G1 cell cycle phase. Consistently, almost 50% of the cells were in early apoptosis and showed remarkable increased expression of caspase-9 (CASP 9). H3 impaired dramatically the adhesiveness of MCF7 cells in culture. Assays conducted with Lysotracker Red probe showed increased organelle acidity, suggesting autophagic cell death, which was further supported by increased expression of microtubuleassociated protein light chain 3 (LC3) and observable conversion of LC3-I in LC3-II by western blot. CONCLUSION: The apoptotic effect of H3 may be related to a balance between apoptotic and autophagic cell death, mediated by increased expression of CASP 9 and LC3-II. To the best of our knowledge this is the first report about a sponge lectin triggering both apoptosis and autophagy in MCF7 cell.