Shewanella goraebulensis sp. nov., isolated from sea water.

A novel Gram-stain-negative, facultatively anaerobic and rod-shaped bacterial strain, designated as DAU312T, was isolated from the sea water of the eastern coast of the Republic of Korea. Optimal growth was observed at 25 °C, pH 7.0-8.0 and with NaCl concentrations of 2.0 % (w/v). Catalase and oxidase activities were detected. On the basis of 16S rRNA gene sequences, strain DAU312T showed the highest similarity (99.2 %) to the type strain Shewanella electrodiphila MAR441T. The complete genome sequence of strain DAU312T contains 4 893 483 bp and 40.5 mol% G+C. Phylogenetic analyses based on 16S rRNA gene sequences and the up-to-date bacterial core genes showed that strain DAU312T, S. electrodiphila MAR441T and S. olleyana were all part of the same monophyletic clade. Their average nucleotide identity, digital DNA-DNA hybridization and two-way average amino acid identity values with each other and type strains of close Shewanella species were 83.4-77.5 %, 27.3-22.0 % and 89.8-81.2 %, respectively. The major cellular fatty acids (>10 %) were iso-C15 : 0, summed feature 3 (C16 : 1 ω7с and/or C16 : 1 ω6с) and C16 : 0. Phosphatidylethanolamine and phosphatidylglycerol were the main polar lipids. The respiratory quinones were Q-7, Q-8, MK-7 and MMK-7. Based on these polyphasic taxonomic findings, the name Shewanella goraebulensis sp. nov. is suggested for strain DAU312T, which is considered to represent a novel species of the genus Shewanella. The type strain is DAU312T (=KCTC 72427 T=JCM 35744T=KCCM 43478T).

Anticancer and Apoptotic Activity in Cervical Adenocarcinoma HeLa Using Crude Extract of Ganoderma applanatum.

Cancer is currently one of the foremost health challenges and a leading cause of death worldwide. Cervical cancer is caused by cofactors, including oral contraceptive use, smoking, multiparity, and HIV infection. One of the major and considerable etiologies is the persistent infection of the oncogenic human papilloma virus. G. applanatum is a valuable medicinal mushroom that has been widely used as a folk medicine for the treatment and prevention of various diseases. In this study, we obtained crude extract from G. applanatum mushroom with a subcritical water extraction method; cell viability assay was carried out and the crude extract showed an antiproliferative effect in HeLa cells with IC50 of 1.55 ± 0.01 mg/mL; however, it did not show any sign of toxicity in HaCaT. Protein expression was detected by Western blot, stability of IκBα and downregulation of NFκB, IKKα, IKKß, p-NFκB-65(Ser 536) and p-IKKα/ß(Ser 176/180), suggesting loss of survival in a dose-dependent manner. RT-qPCR revealed RNA/mRNA expression; fold changes of gene expression in Apaf-1, caspase-3, cytochrome-c, caspase-9, Bax and Bak were increased, which implies apoptosis, and NFκB was decreased in a dose-dependent manner. DNA fragmentation was seen in the treatment groups as compared to the control group using gel electrophoresis. Identification and quantification of compounds were carried out by GC-MS and HPLC, respectively; 2(5H)furanone with IC50 of 1.99 ± 0.01 µg/mL could be the responsible anticancer compound. In conclusion, these findings suggest the potential use of the crude extract of G. applanatum as a natural source with anticancer activity against cervical cancer.

Design, synthesis and evaluation of anticancer activity of new pyrazoline derivatives by down-regulation of VEGF: Molecular docking and apoptosis inducing activity.

Two series of pyrazoline compounds were designed and synthesized as antiproliferative agents by VEGFR pathway inhibition. All synthesized compounds were screened by the National Cancer Institute (NCI), Bethesda, USA for anticancer activity against 60 human cancer cell lines. Compound 3f exhibited the highest anticancer activity on the ovarian cell line (OVCAR-4) with IC50 = 0.29 µM and on the breast cell line (MDA-MB-468) with IC50 = 0.35 µM. It also exhibited the highest selectivity index (SI = 74). Compound 3f caused cell cycle arrest in OVCAR-4 cell line at the S phase which consequently inhibited cell proliferation and induced apoptosis. Moreover, 3f showed potent down-regulation of VEGF and p-VEGFR-2. Docking studies showed that compound 3f interacts in a similar pattern to axitinib on the VEGFR-2 receptor. The same compound was also able to fit into the gorge of STAT3 binding site, the transcription factor for VEGF, which explains the VEGF down-regulation.

Probiotic Treatment Enhances Pre-feeding Larval Development and Early Survival in Zebrafish Danio rerio.

The growth and development of healthy culture subjects are essential in increasing productivity in the aquaculture industry. A primary determinant of aquatic animal productivity is the ambient microbial population. If an aquatic animal's microbiome is diverse, with bacteria favoring beneficial over pathogenic species, the health and growth of the animal (i.e., fish or crustacean) can be substantially improved. Embryonic and newly hatched Zebrafish Danio rerio larvae were reared in the presence of (1) water from the broodstock culture tank as a control, (2) a probiotic solution containing 19 strains of live lactic acid bacteria (LAB), or (3) an antibiotic (AB) solution with amoxycillin. Developmental parameters were monitored until 10 d postfertilization. Bacteria present in the water and larvae were cultured and identified by sequencing the V4 hypervariable region of bacterial 16S ribosomal RNA. Probiotic-treated larvae showed significant increases in every measured morphological parameter and in survival compared to the controls and AB-treated larvae, including TL, eye development, and swim bladder development before first feeding. Staining with DASPEI (2-(4-[dimethylamino]styryl)-N-ethylpyridinium iodide) produced fluorescence, revealing increased mitochondrial activity in the gastrointestinal tracts of probiotic-treated larvae and reflecting advancement of initial metabolic function. Probiotic-treated larvae showed accelerated yolk absorption, resulting in increased nutrient mobilization and growth. Microbial analyses revealed a greater concentration of bacteria in larvae in response to the probiotic treatment compared to the other two treatments. Species identified in all three treatments included Pseudomonas spp. and Aeromonas spp. (Proteobacteria). The second most diverse and abundant microbiome was seen in controls, whereas AB-treated larvae had the least diverse microbiome. All treatments revealed the presence of proteobacteria, but an AB-resistant pathogenic bacterium (Stenotrophomonas maltophilia) was identified in the AB group. These results reveal that the presence of LAB and other bacteria favorably influenced early larval growth, development, digestive function, and survival in Zebrafish even before the onset of feeding.

Histological and impedance changes of skeletal muscle by whole-body critical irradiation in a rat model.

In this study, the electrical resistance of the whole body and histological changes of skeletal muscle were investigated in rats according to the increase in radiation dose. A total of 15 male Sprague-Dawley rats (5-weeks-old) were randomly divided into 5 groups (each, n = 3). Each group received 1 Gy, 5 Gy, 10 Gy and 20 Gy systemic exposure, and the non-irradiated group was used as a control for morphological comparison. After attaching an electrode clip to the forelimb of the rat, an AC frequency was applied before and 4 days after irradiation using an impedance/gain-phase analyzer, and the measurement system was automatically controlled with LabVIEW. Comparing to before irradiation after 4 days, the difference in the average impedance values at 1 Gy, 5 Gy, 10 Gy, and 20 Gy was 1188±989 ohm, 3076±2251 ohm, 7650±6836 ohm, and 10478±6250 ohm, respectively. By comparing the normal group and the experimental group, muscle fiber atrophy and collagen fibers around blood vessels were observed (p < 0.05, control group vs 5 Gy or more high-dose group). These results confirmed the previously reported morphological changes of skeletal muscle and our hypothesis that whole-body impedance measurement enables to reflect tissue changes after irradiation.

Anticancer and Immunomodulatory Effects of Polysaccharides.

Cancer is one of the leading causes of death and one of the most important public health problems in the world. And every year, millions of new cancers and hundreds of thousands of cancer-related deaths are reported worldwide. In recent decades, a number of biologically active polysaccharides and polysaccharide-protein complexes have been isolated from plants, lichen, algae, yeast, fungi and mushroom, and due to their antitumor and immunomodulatory properties, these compounds have received considerable attention. Overall, the two key mechanisms by which polysaccharides act on tumor cells are direct action (inhibition of cancer cell growth and induction of programmed cell death/apoptosis) and indirect action (stimulation of immunity). Immunosuppressive effects are recognizable in both cancer patients and tumor bearing animals, suggesting that the immune system plays an important role in the immune surveillance of cancer cells. Thus, enhancement of the host immune response has been evaluated as a possible way of inhibiting tumor growth without damaging the host. In addition to their therapeutic and prophylactic properties, the polysaccharides are effective and less toxic than chemotherapy. The anticancer activity and immunomodulatory effects of most polysaccharides have shown the promising and real potential for the benefits of human health.

Design and synthesis of methoxyphenyl- and coumarin-based chalcone derivatives as anti-inflammatory agents by inhibition of NO production and down-regulation of NF-κB in LPS-induced RAW264.7 macrophage cells.

Exaggerated inflammatory responses may cause serious and debilitating diseases such as acute lung injury and rheumatoid arthritis. Two series of chalcone derivatives were prepared as anti-inflammatory agents. Methoxylated phenyl-based chalcones 2a-l and coumarin-based chalcones 3a-f were synthesized and compared for their inhibition of COX-2 enzyme and nitric oxide production suppression. Methoxylated phenyl-based chalcones showed better inhibition to COX-2 enzyme and nitric oxide suppression than the coumarin-based chalcones. Among the 18 synthesized chalcone derivatives, compound 2f exhibited the highest anti-inflammatory activity by inhibition of nitric oxide concentration in LPS-induced RAW264.7 macrophages (IC50 = 11.2 µM). The tested compound 2f showed suppression of iNOS and COX-2 enzymes. Moreover, compound 2f decreases in the expression of NF-κB and phosphorylated IκB in LPS-stimulated macrophages. Finally, docking studies suggested the inhibition of IKKß as a mechanism of action and highlighted the importance of 2f hydrophobic interactions.

Changes of electrical impedance characteristics with the radiation induced damage on biological tissue constituents.

This study analyzes the response of increasing radiation dose to the pork tenderloin tissue. Considering its significant cell structure, pork tenderloin tissue samples are selected for the experimental objects to measure their electrical impedance characteristics. This study proposes and investigates an effective approach to characterize the variation of the internal change of the components of pork tenderloin tissues caused by radiation. Changes in the pork tenderloin tissues are that the gap of the myotome is more far apart with increase of radiation dose because of the destroyed Myofibrils under the damage. With the increase of radiation dose, the impedance value of the pork tenderloin tissue decreases. Each of mean differences in the impedance values before and after irradiation dose under 1 Gy, 2 Gy and 4 Gy show 0.55±0.03, 1.09±0.14 and 1.97±0.14, respectively. However, the mean difference substantially increases to 13.08±0.16 at irradiation dose of 10 Gy. Thus, the cell membrane shows the most severe rupture at a radiation dose of 10 Gy. Changes in the microstructure of the irradiated pork tenderloin tissue samples are also checked and validated by a transmission electron microscope.

Anti-Inflammatory Activity of ß-thymosin Peptide Derived from Pacific Oyster (Crassostrea gigas) on NO and PGE2 Production by Down-Regulating NF-κB in LPS-Induced RAW264.7 Macrophage Cells.

ß-thymosin is known for having 43 amino acids, being water-soluble, having a light molecular weight and ubiquitous polypeptide. The biological activities of ß-thymosin are diverse and include the promotion of wound healing, reduction of inflammation, differentiation of T cells and inhibition of apoptosis. Our previous studies showed that oyster ß-thymosin originated from the mantle of the Pacific oyster, Crassostrea gigas and had antimicrobial activity. In this study, we investigated the anti-inflammatory effects of oyster ß-thymosin in lipopolysaccharide (LPS)-induced RAW264.7 macrophage cells using human ß-thymosin as a control. Oyster ß-thymosin inhibited the nitric oxide (NO) production as much as human ß-thymosin in LPS-induced RAW264.7 cells. It also showed that oyster ß-thymosin suppressed the expression of prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, oyster ß-thymosin reduced inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6). Oyster ß-thymosin also suppressed the nuclear translocation of phosphorylated nuclear factor-κB (NF-κB) and degradation of inhibitory κB (IκB) in LPS-induced RAW264.7 cells. These results suggest that oyster ß-thymosin, which is derived from the mantle of the Pacific oyster, has as much anti-inflammatory effects as human ß-thymosin. Additionally, oyster ß-thymosin suppressed NO production, PGE2 production and inflammatory cytokines expression via NF-κB in LPS-induced RAW264.7 cells.

Cristazine, a novel dioxopiperazine alkaloid, induces apoptosis via the death receptor pathway in A431 cells.

The fungus Chaetomium sp. is a causative agent of infections in humans and is ubiquitous in the natural environment. The secondary metabolites of this genus exhibit many biological activities, including antifungal activity and toxicity in mitochondria. In this study, we isolated cristazine from the fungus C. cristatum, which has the potential to inhibit the growth of human epidermoid carcinoma (A431) cells in a dose- and time-dependent manner. Its inhibitory activity was examined using a cell viability assay and cell death was elucidated by western blot analysis. Cristazine triggered apoptotic cell death via the Type I death receptor pathway including the activation of caspases and other target proteins. However, cristazine did not have any effect on mitochondrial apoptotic proteins such as Bid, cytochrome c, and apoptosis-inducing factor. Cristazine inhibited the cell cycle progression by arresting the G1 /S phase and up-regulating the inhibitory proteins of cyclin-dependent kinases. Thus, cristazine has great potential for inducing apoptosis in A431 cells via both cell cycle arrest and the inhibition of cell growth.

Morphological changes of bacterial cells upon exposure of silver-silver chloride nanoparticles synthesized using Agrimonia pilosa.

Facile, eco-friendly synthesis of metal nanoparticles has been proposed as a cost effective method. In the present study, we propose the facile synthesis of silver-silver chloride (Ag-AgCl) nanoparticles (NPs) using the medicinally important Agrimonia pilosa plant extract without addition of capping or stabilizing agents. The Ag-AgCl NPs synthesis was observed at 40 °C after 10 min incubation; the synthesis of Ag-AgCl NPs was indicated by color change and confirmed by UV-vis spectroscopic peak at 454 nm. TEM analysis confirmed Ag-AgCl NPs were 10-20 nm in size and spherical, and oval in shape. Elemental composition was determined by energy dispersive X-ray analysis, and crystalline structure was confirmed by X-ray diffraction spectroscopy. Different phytocomponents present in the plant extract were analyzed by Gas Chromatography-Mass spectrometry, and the interaction of biomolecules in reduction process was analyzed by Fourier transform infrared spectroscopy studies. The synthesized Ag-AgCl NPs showed significant antibacterial efficiency, analyzed by well diffusion assay against pathogenic bacteria including Bacillus cereus, Listeria monocytogenes, Staphylococcus aureus, Staphylococcus saprophyticus, Escherichia coli, Pseudomonas putida. Minimum inhibitory concentration and minimum bactericidal concentration were evaluated by microbroth dilution, and spread plate method, respectively. The possible mechanism of bacterial growth inhibition is due to changes in bacterial cell wall morphology that was studied by FE-SEM analysis.

Antibacterial potential of silver nanoparticles synthesized using Madhuca longifolia flower extract as a green resource.

The green and one-step synthesis of silver nanoparticles (AgNPs) has been proposed as simple and ecofriendly. In the present study, a flower extract of Madhuca longifolia was used for the reduction of silver nitrate into AgNPs, with phytochemicals from the flower extract as a reducing and stabilizing agents. The synthesized AgNPs were spherical and oval shaped and about 30-50 nm sizes. The appearance of a brown color in the reaction mixture is a primary indication of AgNPs formation, and it was confirmed by observing UV-visible spectroscopy peak at 436 nm. The Energy Dispersive X-ray spectra and X-ray diffraction analysis results together confirm that the synthesized nanoparticles contain silver and silver chloride nanoparticles. The Zeta potential analysis indicates presence of negative charges on synthesized AgNPs. The FT-IR study represents involvement of functional groups in AgNPs synthesis. Synthesized AgNPs shows potential antibacterial activity against Gram-positive and Gram-negative pathogens. M. longifolia flower is a good source for AgNPs synthesis and synthesized AgNPs are applicable as antibacterial agent in therapeutics.

Anti-Inflammatory Effects of Aster incisus through the Inhibition of NF-κB, MAPK, and Akt Pathways in LPS-Stimulated RAW 264.7 Macrophages.

Aster incisus is a common flower found in almost all regions of South Korea. In the current study, we investigated the potential antioxidant and anti-inflammatory properties of the Aster incisus methanol extract in LPS-stimulated RAW 264.7 cells. We analyzed the phytochemicals contained in the extract by GC-MS. GC-MS results showed that the Aster incisus extract contains 9 known compounds. Later on, DPPH assay, WST-1 assay, nitric oxide (NO) assay, Western blot, and RT-PCR were conducted to investigate the anti-inflammatory effects of the extract. Our WST-1 assay results revealed that Aster incisus did not affect the viability of all tested cell lines up to a concentration of 200 µg/ml; therefore, lower concentrations (50 µg/ml and 150 µg/ml) were used for further assays. Aster incisus scavenged DPPH and inhibited the production of NO. Aster incisus also reduced significantly the production of inflammation-related enzymes (iNOS, Cox-2) and cytokines (TNFα, IL-1ß, and IL-6) and the gene expression of the proinflammatory cytokines. Additionally, further Western blot results indicated that Aster incisus inhibited the expression of p-PI3K, p-IκBα, p-p65 NF-κB, p-ERK1/2, p-SAPK/JNK, and p-Akt. Our results demonstrated that Aster incisus suppressed the expression of the inflammation mediators through the regulation of NF-κB, MAPK, and Akt pathways.

Eco-friendly approach for nanoparticles synthesis and mechanism behind antibacterial activity of silver and anticancer activity of gold nanoparticles.

This review covers general information about the eco-friendly process for the synthesis of silver nanoparticles (AgNP) and gold nanoparticles (AuNP) and focuses on mechanism of the antibacterial activity of AgNPs and the anticancer activity of AuNPs. Biomolecules in the plant extract are involved in reduction of metal ions to nanoparticle in a one-step and eco-friendly synthesis process. Natural plant extracts contain wide range of metabolites including carbohydrates, alkaloids, terpenoids, phenolic compounds, and enzymes. A variety of plant species and plant parts have been successfully extracted and utilized for AgNP and AuNP syntheses. Green-synthesized nanoparticles eliminate the need for a stabilizing and capping agent and show shape and size-dependent biological activities. Here, we describe some of the plant extracts involved in nanoparticle synthesis, characterization methods, and biological applications. Nanoparticles are important in the field of pharmaceuticals for their strong antibacterial and anticancer activity. Considering the importance and uniqueness of this concept, the synthesis, characterization, and application of AgNPs and AuNPs are discussed in this review.

Autophagy and Inflammatory Response in the Tumor Microenvironment.

Cell death is the last fate of the life cycle of cells. Different pathways involved in cell death are known to date, and are mostly represented by apoptosis, necrosis, and autophagy. Autophagy is one of the most preserved cell death pathways, characterized by the elimination of large parts of cytoplasmic components after being consumed by a double-membraned vesicle called an autophagosome. The formed autophagosome then fuses with a lysosome containing degrading enzymes and leads to the digestion of the autophagosome content. Autophagy is triggered by stress-related inducers, and is partially dependent on apoptotic proteins. It plays a major role in cancer, particularly in the tumor microenvironment where it has a paradoxical function in acting as a tumor suppressor and also as a tumor promoter. In the tumor microenvironment, autophagy regulates the differentiation of macrophages into tumor-associated macrophages (TAMs) and fibroblasts into cancer-associated fibroblasts (CAFs). TAMs and CAFs are abundantly present in the tumor microenvironment, and participate actively in tumor growth, tumor invasiveness, and tumor resistance to chemotherapy.

Cristazine, a New Cytotoxic Dioxopiperazine Alkaloid from the Mudflat-Sediment-Derived Fungus Chaetomium cristatum.

Cristazine (1), a new class of dioxopiperazine alkaloid, along with previously isolated chetomin (2), neoechinulin A (3), and golmaenone (4), were isolated from the mudflat-sediment-derived fungus Chaetomium cristatum. The structure and absolute stereochemistry of 1 was assigned on the basis of NMR, electron impact (EI)-MS, tandem FAB-MS/MS, and circular dichroism (CD) experiments. Compounds 1-4 displayed potent radical-scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH), with IC50 values of 19, 15, 24, and 20 µM, respectively, which were similar to that of the positive control, ascorbic acid (IC50, 20 µM). Compound 1 also displayed cytotoxic activity against human cervical carcinoma (HeLa) cells, with an IC50 value of 0.5 µM.

Apoptotic Cell Death Induced by ofLBP6A, Lipopolysaccharide Binding Protein Model Peptide, Derived from Paralichthy olivaceus on MKN-28 Cells.

The aim of this study was to evaluate the anti-cancer effects of lipopolysaccharide binding protein (LBP) analogs derived from the marine resource Paralichthy olivaceus on MKN-28 gastric cancer cells. Five LBP analogs were used: ofLBP1N, ofLBP2A, ofLBP4N, ofLBP5A, and ofLBP6A. ofLBP6A induced cell death of MKN-28 cells at a concentration of 40 µM. While the anti-proliferation effects ofLBP6A showed on MKN-28 cells at concentration of 40 µM, it did not affect non-cancerous HEK-293 cells at the same concentration. The mechanism study showed that ofLBP6A lead to the inhibition of cell proliferation by apoptosis along with morphological changes. The phosphorylation of Fas associated death domain (FADD) as well as the expressions of cleaved caspase-8, -7, and -3 were increased by ofLBP6A treatment. Increased the expression level of cleaved caspase-3 was confirmed by immunofluorescence staining. The expressions of Bid, Bax, and cytochrome C were also increased by the treatment. However, the expressions of cellular FLICE (FADD-like IL-1ß-converting enzyme)-inhibitory protein (FLIP), Bcl-XL, and Bcl-2 were decreased by ofLBP6A treatment. The results of this study were the first to demonstrate the apoptotic anti-cancer effects of ofLBP6A, derived from P. olivavaceus on gastric cancer cells.

Antimetastatic effects of gambogic acid are mediated via the actin cytoskeleton and NF-κB pathways in SK-HEP1 cells.

Hepatocellular carcinoma (HCC) is one of the most malignant and frequent cancers with a high metastatic potential. The prevention of HCC metastasis is a critical target for effective therapies in HCC. Gambogic acid (GA), a natural compound obtained from Garcinia hanburyi has reported anticancer activity in cell lines. However, the antimetastatic mechanisms of GA are unclear, particularly with respect to HCC. In this study, the influence of GA on migration and invasion of SK-HEP1 cells was evaluated. At concentrations above 0.6 µM, GA reduced cell proliferation in SK-HEP1 cells without affecting proliferation of noncancerous HEK-293 cells. GA also suppressed migration and invasion of SK-HEP1 cells. GA downregulated the expression of the integrin ß1/rho family GTPase signaling pathway, suppressed the actin rearrangement related to cell cytoskeleton and migration and decreased matrix metalloproteinases MMP-2, MMP-9, and NF-κB expression involved in cancer invasion. These results suggest that GA may be a potential lead in developing an antimetastatic therapeutic for the treatment of HCC.

Differentially-Expressed Genes Associated with Faster Growth of the Pacific Abalone, Haliotis discus hannai.

The Pacific abalone Haliotis discus hannai is used for commercial aquaculture in Korea. We examined the transcriptome of Pacific abalone Haliotis discus hannai siblings using NGS technology to identify genes associated with high growth rates. Pacific abalones grown for 200 days post-fertilization were divided into small-, medium-, and large-size groups with mean weights of 0.26 ± 0.09 g, 1.43 ± 0.405 g, and 5.24 ± 1.09 g, respectively. RNA isolated from the soft tissues of each group was subjected to RNA sequencing. Approximately 1%-3% of the transcripts were differentially expressed in abalones, depending on the growth rate. RT-PCR was carried out on thirty four genes selected to confirm the relative differences in expression detected by RNA sequencing. Six differentially-expressed genes were identified as associated with faster growth of the Pacific abalone. These include five up-regulated genes (including one specific to females) encoding transcripts homologous to incilarin A, perlucin, transforming growth factor-beta-induced protein immunoglobulin-heavy chain 3 (ig-h3), vitelline envelope zona pellucida domain 4, and defensin, and one down-regulated gene encoding tomoregulin in large abalones. Most of the transcripts were expressed predominantly in the hepatopancreas. The genes identified in this study will lead to development of markers for identification of high-growth-rate abalones and female abalones.

3,4-dihydroxyphenyl acetic acid and (+)-epoxydon isolated from marine algae-derived microorganisms induce down regulation of epidermal growth factor activated mitogenic signaling cascade in Hela cells.

BACKGROUND: Epidermal growth factor receptor (EGFR) is a member of the receptor tyrosine kinase (RTK) family. Epidermal growth factor induces its dimerization and stimulates phosphorylation of intracellular tyrosine residues. Phosphorylation of EGFR is studied for cancer therapy because EGFR regulates many cellular processes including cell proliferation, differentiation, and survival. Hence, down-regulation of EGFR kinase activity results in inhibition of signaling cascades amenable for proliferation and progression of cell cycle. METHODS: In the study, we purified 3,4-dihydroxyphenyl acetic acid and (+)-epoxydon from Aspergillus sp. isolated from marine brown alga Ishige okamurae and Phoma herbarum isolated from marine red alga Hypnea saidana respectively and determined its anti-tumor activities against HeLa human cervical cancer cells. RESULTS: Two compounds suppressed EGFR activity in vitro with IC50 values for 3,4-dihydroxyphenyl acetic acid and (+)-epoxydon were 2.8 and 0.6 µg/mL respectively and reduced the viable numbers of HeLa cells. Immunoblotting analysis exhibited that the compounds induced inhibition of cell growth by causing downregulation of the mitogenic signaling cascade, inactivation of p90RSK, and release of cytochrome c from mitochondria. CONCLUSIONS: Results suggest that decreased expression of active EGFR and EGFR-related downstream molecules by treatment with the compounds may results in the inhibition of cell growth and inducement of apoptosis.