Publications by authors named "Kwang-Hee Son"

51 Publications

Statistical optimization of culture medium for improved production of antimicrobial compound by AG-P1441.

Food Sci Biotechnol 2018 Apr 16;27(2):581-590. Epub 2017 Dec 16.

1Industrial Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon, 34141 Korea.

The nutritional requirements for antimicrobial activity of AG-P1441 were optimized using statistically-based experimental designs at a flask level. Based on a one-factor-at-a-time (OFAT) approach, glucose, corn starch and soybean meal were identified as the carbon and nitrogen sources having a significant effect on antimicrobial productivity. As a result of investigating the effect of glucose concentration, the highest antimicrobial activity was observed at 3% concentration. Response surface methodology (RSM) was then applied to optimize the growth medium components (corn starch, soybean meal, MgCl and glutamate). Antimicrobial productivity increased sharply when the medium consisted of 3% glucose, 3.5% corn starch, 2.5% soybean meal, 1.2 mM MgCl and 5.9 mM glutamate. The fermentation using optimized culture medium in a 5-L bioreactor allowed a significant increase in antimicrobial activity, evaluated by the paper disc assay, revealed a 29 mm inhibition zone diameter against .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10068-017-0257-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6049630PMC
April 2018

Genetic and functional characterization of a novel GH10 endo-β- 1,4-xylanase with a ricin-type β-trefoil domain-like domain from Luteimicrobium xylanilyticum HY-24.

Int J Biol Macromol 2018 Jan 13;106:620-628. Epub 2017 Aug 13.

Industrial Bio-Materials Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea. Electronic address:

The gene (1488-bp) encoding a novel GH10 endo-β-1,4-xylanase (XylM) consisting of an N-terminal catalytic GH10 domain and a C-terminal ricin-type β-trefoil lectin domain-like (RICIN) domain was identified from Luteimicrobium xylanilyticum HY-24. The GH10 domain of XylM was 72% identical to that of Micromonospora lupini endo-β-1,4-xylanase and the RICIN domain was 67% identical to that of Actinospica robiniae hypothetical protein. The recombinant enzyme (rXylM: 49kDa) exhibited maximum activity toward beechwood xylan at 65°C and pH 6.0, while the optimum temperature and pH of its C-terminal truncated mutant (rXylM△RICIN: 35kDa) were 45°C and 5.0, respectively. After pre-incubation of 1h at 60°C, rXylM retained over 80% of its initial activity, but the thermostability of rXylM△RICIN was sharply decreased at temperatures exceeding 40°C. The specific activity (254.1Umg) of rXylM toward oat spelts xylan was 3.4-fold higher than that (74.8Umg) of rXylM△RICIN when the same substrate was used. rXylM displayed superior binding capacities to lignin and insoluble polysaccharides compared to rXylM△RICIN. Enzymatic hydrolysis of β-1,4-d-xylooligosaccharides (X-X) and birchwood xylan yielded X as the major product. The results suggest that the RICIN domain in XylM might play an important role in substrate-binding and biocatalysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijbiomac.2017.08.063DOI Listing
January 2018

Biocatalytic characterization of an endo-β-1,4-mannanase produced by Paenibacillus sp. strain HY-8.

Biotechnol Lett 2017 Jan 6;39(1):149-155. Epub 2016 Oct 6.

Industrial Bio-materials Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, Republic of Korea.

Objectives: To evaluate the biocatalytic characteristics of a new endo-β-1,4-D-mannan-degrading enzyme (ManP) from Paenibacillus sp. strain HY-8, a gut bacterium of the longicorn beetle Moechotypa diphysis.

Results: Purified ManP (32 kDa) with an N-terminal amino acid sequence of APSFAVGADFSYVPG displayed the greatest degree of biocatalytic activity toward locust bean gum (LBG) at 55 °C and pH 7.0. The enzyme degraded LBG, guar gum, ivory nut mannan, and mannooligosaccharides (M-M), but did not exhibit any hydrolytic activity against structurally unrelated substrates. The biocatalytic activity of ManP against LBG and guar gum was 695 and 450 U mg, respectively. Especially, enzymatic hydrolysis of mannobiose yielded a mixture of mannose (16.6 %) and mannobiose (83.4 %), although the degree of mannobiose degradation by ManP with was relatively limited.

Conclusion: The present results suggest that ManP is an endo-β-1,4-mannanase and is distinct from various other characterized endo-β-1,4-mannanases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10529-016-2228-7DOI Listing
January 2017

Genetic and functional characterization of an extracellular modular GH6 endo-β-1,4-glucanase from an earthworm symbiont, Cellulosimicrobium funkei HY-13.

Antonie Van Leeuwenhoek 2016 01 19;109(1):1-12. Epub 2015 Oct 19.

Industrial Bio-materials Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 305-806, Republic of Korea.

The gene (1608-bp) encoding a GH6 endo-β-1,4-glucanase (CelL) from the earthworm-symbiotic bacterium Cellulosimicrobium funkei HY-13 was cloned from its whole genome sequence, expressed recombinantly, and biochemically characterized. CelL (56.0 kDa) is a modular enzyme consisting of an N-terminal catalytic GH6 domain (from Val57 to Pro396), which is 71 % identical to a GH6 protein (accession no.: WP_034662937) from Cellulomonas sp. KRMCY2, together with a C-terminal CBM 2 domain (from Cys429 to Cys532). The highest catalytic activity of CelL toward carboxymethylcellulose (CMC) was observed at 50 °C and pH 5.0, and was relatively stable at a broad pH range of 4.0-10.0. The enzyme was capable of efficiently hydrolyzing the cellulosic polymers in the order of barley β-1,3-1,4-D-glucan > CMC > lichenan > Avicel > konjac glucomannan. However, cellobiose, cellotriose, p-nitrophenyl derivatives of mono- and disaccharides, or structurally unrelated carbohydrate polymers including β-1,3-D-glucan, β-1,4-D-galactomannan, and β-1,4-D-xylan were not susceptible to CelL. The enzymatic hydrolysis of cellopentaose resulted in the production of a mixture of 68.6 % cellobiose and 31.4 % cellotriose but barley β-1,3-1,4-D-glucan was 100 % degraded to cellotriose by CelL. The enzyme strongly bound to Avicel, ivory nut mannan, and chitin but showed relatively weak binding affinity to lichenan, lignin, or poly(3-hydroxybutyrate) granules.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10482-015-0604-2DOI Listing
January 2016

Glycogen Synthase Kinase-3β (GSK-3β) Inhibition Enhances Dendritic Cell-based Cancer Vaccine Potency via Suppression of Interferon-γ-induced Indoleamine 2,3-Dioxygenase Expression.

J Biol Chem 2015 May 26;290(19):12394-402. Epub 2015 Mar 26.

the Department of Immunology, Laboratory of Dendritic Cell Differentiation and Regulation, Konkuk University School of Medicine, Chungju 380-701, South Korea

Indoleamine 2,3-dioxygenase (IDO) functions as a crucial mediator of tumor-mediated immune tolerance by causing T-cell suppression via tryptophan starvation in a tumor environment. Glycogen synthase kinase-3β (GSK-3β) is also involved in immune and anti-tumor responses. However, the relativity of these proteins has not been as well defined. Here, we found that GSK-3β-dependent IDO expression in the dendritic cell (DC) plays a role in anti-tumor activity via the regulation of CD8(+) T-cell polarization and cytotoxic T lymphocyte activity. By the inhibition of GSK-3β, attenuated IDO expression and impaired JAK1/2-Stat signaling crucial for IDO expression were observed. Protein kinase Cδ (PKCδ) activity and the interaction between JAK1/2 and Stat3, which are important for IDO expression, were also reduced by GSK-3β inhibition. CD8(+) T-cell proliferation mediated by OVA-pulsed DC was blocked by interferon (IFN)-γ-induced IDO expression via GSK-3β activity. Specific cytotoxic T lymphocyte activity mediated by OVA-pulsed DC against OVA-expressing EG7 thymoma cells but not OVA-nonexpressing EL4 thymoma cells was also attenuated by the expressed IDO via IFN-γ-induced activation of GSK-3β. Furthermore, tumor growth that was suppressed with OVA-pulsed DC vaccination was restored by IDO-expressing DC via IFN-γ-induced activation of GSK-3β in an OVA-expressing murine EG7 thymoma model. Taken together, DC-based immune response mediated by interferon-γ-induced IDO expression via GSK-3β activity not only regulates CD8(+) T-cell proliferation and cytotoxic T lymphocyte activity but also modulates OVA-pulsed DC vaccination against EG7 thymoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1074/jbc.M114.628578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4424368PMC
May 2015

Biocatalytic properties and substrate-binding ability of a modular GH10 β-1,4-xylanase from an insect-symbiotic bacterium, Streptomyces mexicanus HY-14.

J Microbiol 2014 Oct 1;52(10):863-70. Epub 2014 Oct 1.

Industrial Bio-materials Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 305-806, Republic of Korea.

The gene (1350-bp) encoding a modular β-1,4-xylanase (XylU), which consists of an N-terminal catalytic GH10 domain and a C-terminal carbohydrate-binding module 2 (CBM 2), from Streptomyces mexicanus HY-14 was cloned and functionally characterized. The purified His-tagged recombinant enzyme (rXylU, 44.0 kDa) was capable of efficiently hydrolyze diverse xylosidic compounds, p-nitrophenyl-cellobioside, and p-nitrophenyl-xylopyranoside when incubated at pH 5.5 and 65°C. Especially, the specific activities (649.8 U/mg and 587.0 U/mg, respectively) of rXylU toward oat spelts xylan and beechwood xylan were relatively higher than those (<500.0 U/mg) of many other GH10 homologs toward the same substrates. The results of enzymatic degradation of birchwood xylan and xylooligosaccharides (xylotriose to xylohexaose) revealed that rXylU preferentially hydrolyzed the substrates to xylobiose (>75%) as the primary degradation product. Moreover, a small amount (4%<) of xylose was detected as the degradation product of the evaluated xylosidic substrates, indicating that rXylU was a peculiar GH10 β-1,4-xylanase with substrate specificity, which was different from its retaining homologs. A significant reduction of the binding ability of rXylU caused by deletion of the C-terminal CBM 2 to various insoluble substrates strongly suggested that the additional domain might considerably contribute to the enzyme-substrate interaction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12275-014-4390-8DOI Listing
October 2014

Novel alkali-tolerant GH10 endo-β-1,4-xylanase with broad substrate specificity from Microbacterium trichothecenolyticum HY-17, a gut bacterium of the mole cricket Gryllotalpa orientalis.

J Microbiol Biotechnol 2014 Jul;24(7):943-53

Industrial Bio-materials Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-806, Republic of Korea.

The XylH gene (1,167-bp) encoding a novel hemicellulase (41,584 Da) was identified from the genome of Microbacterium trichothecenolyticum HY-17, a gastrointestinal bacterium of Gryllotalpa orientalis. The enzyme consisted of a single catalytic domain, which is 74% identical to that of an endo-β-1,4-xylanase (GH10) from Isoptericola variabilis 225. Unlike other endo-β- 1,4-xylanases from invertebrate-symbiotic bacteria, rXylH was an alkali-tolerant multifunctional enzyme possessing endo-β-1,4-xylanase activity together with β-1,3/β-1,4- glucanase activity, which exhibited its highest xylanolytic activity at pH 9.0 and 60°C, and was relatively stable within a broad pH range of 5.0-10.0. The susceptibilities of different xylosebased polysaccharides to the XylH were assessed to be as follows: oat spelts xylan > beechwood xylan > birchwood xylan > wheat arabinoxylan. rXylH was also able to readily cleave p-nitrophenyl (pNP) cellobioside and pNP-xylopyranoside, but did not hydrolyze other pNP-sugar derivatives, xylobiose, or hexose-based materials. Enzymatic hydrolysis of birchwood xylan resulted in the product composition of xylobiose (71.2%) and xylotriose (28.8%) as end products.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4014/jmb.1405.05032DOI Listing
July 2014

Effect of arazyme on the lipopolysaccharide‑induced inflammatory response in human endothelial cells.

Mol Med Rep 2014 Aug 13;10(2):1025-9. Epub 2014 May 13.

Department of Clinical Laboratory Science, Wonkwang Health Science University, Iksan, Chonbuk 570‑750, Republic of Korea.

Arazyme is a novel extracellular metalloprotease secreted by Aranicola proteolyticus. Endothelial cells are involved in the pathogenesis of a number of inflammatory diseases, induce uncontrolled cell viability and express various inflammatory mediators, including cytokines, chemokines, adhesion molecules and reactive oxygen species (ROS). In the current study, human umbilical vein endothelilal cells (HUVECs) were used to investigate the anti‑inflammatory effects of arazyme following lipopolysaccharide (LPS) stimulation. Apoptosis of HUVECs due to LPS was inhibited by arazyme. In various inflammatory responses induced by LPS, arazyme inhibited the secretion of the monocyte chemoattractant protein‑1 and interleukin‑6, and the expression of vascular cell adhesion molecule‑1 and intercellular adhesion molecule‑1. Arazyme also suppressed ROS production in HUVECs. The action of arazyme was not associated with NF‑κB activity in HUVECs. These results indicate that arazyme has anti‑inflammatory properties in inflamed endothelial cells and may be useful as a therapeutic agent for inflammatory diseases associated with endothelial cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/mmr.2014.2231DOI Listing
August 2014

Arazyme inhibits cytokine expression and upregulates skin barrier protein expression.

Mol Med Rep 2013 Aug 13;8(2):551-6. Epub 2013 Jun 13.

Department of Biomedical Laboratory Science, School of Medicine, Eulji University, Daejeon, Chungnam 301‑746, Republic of Korea.

In the present study, the inhibitory effect of arazyme on allergic inflammation was investigated by evaluating the alteration of cytokine production and expression of skin barrier proteins in immune and HaCaT human keratinocyte cells. THP‑1 human monocytic and EoL‑1 human eosinophilic cells were treated with Dermatophagoides pteronissinus extract (DpE). Monocyte chemotactic protein‑1 (MCP‑1)/CCL2, interleukin (IL)‑6 and IL‑8 increased following DpE treatment and arazyme significantly blocked the increase of MCP‑1, IL‑6 and IL‑8 expression in cell types. Secretion of MCP‑1, IL‑6 and IL‑8 induced by lipopolysaccharide in THP‑1 cells was also inhibited by arazyme treatment. Arazyme inhibited the secretion of IL‑6 and IL‑8 due to phorbol 12‑myristate 13‑acetate and calcium ionophores in human mast cells. Arazyme blocked the secretion of thymus and activation‑regulated chemokine (TARC)/CCL17, MCP‑1, IL‑6 and IL‑8 due to tumor necrosis factor‑α (TNF‑α) and interferon‑γ (IFN‑γ) in HaCaT cells. TNF‑α and IFN‑γ suppressed the expression of skin barrier proteins, including filaggrin, involucrin and loricrin. By contrast, arazyme increased the expression of filaggrin, involucrin and loricrin. These results may contribute to the development of a therapeutic drug for the treatment of allergic diseases, including atopic dermatitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/mmr.2013.1520DOI Listing
August 2013

Non-ionic polysorbate surfactants: alternative inducers of medium-chain-length poly(3-hydroxyalkanoates) (MCL-PHAs) for production of extracellular MCL-PHA depolymerases.

Bioresour Technol 2012 Oct 9;121:47-53. Epub 2012 Jul 9.

Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon 305-764, Republic of Korea.

The potential of non-ionic polysorbate surfactants as alternative inducers of medium-chain-length poly(3-hydroxyalkanoates) (MCL-PHAs) for the production of diverse bacterial MCL-PHA depolymerases was evaluated. When grown with corn oil as the sole carbon substrate, Pseudomonas alcaligenes LB19 preferentially produced lipolytic enzymes, but its MCL-PHA depolymerase was not induced by the substrate. However, the results of activity staining and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis clearly revealed that Tween 20 induced simultaneous production of lipolytic enzymes and the MCL-PHA depolymerase with the molecular mass (26.5 kDa) of P. alcaligenes LB19, which has been previously identified. Moreover, the co-production of two functionally distinct hydrolytic enzymes induced by Tween 20 was commonly observed in various Gram-positive and Gram-negative bacteria that were fed the substrate. Thus, it is expected that non-ionic polysorbate surfactants including Tween 20 can be widely exploited as promising universal substrates for the facile and efficient production of diverse MCL-PHA depolymerases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biortech.2012.06.118DOI Listing
October 2012

Protein kinase C δ (PKCδ)-extracellular signal-regulated kinase 1/2 (ERK1/2) signaling cascade regulates glycogen synthase kinase-3 (GSK-3) inhibition-mediated interleukin-10 (IL-10) expression in lipopolysaccharide (LPS)-induced endotoxemia.

J Biol Chem 2012 Apr 5;287(17):14226-33. Epub 2012 Mar 5.

Department of Microbiology and Immunology, School of Medicine, Pusan National University, Yangsan, Gyeongsangnam-do 626-870, South Korea.

Glycogen synthase kinase-3 (GSK-3) modulates a wide array of cellular processes, including embryonic development, cell differentiation, survival, and apoptosis. Recently, it was reported that a GSK-3 inhibitor attenuates lipopolysaccharide (LPS)-induced septic shock and regulates the mortality of endotoxemic mice. However, the detailed mechanism of reduced mortality via GSK-3 inhibition is not well defined. Herein, we showed that GSK-3 inhibition induces extracellular signal-regulated kinase 1/2 (ERK1/2) activation under LPS-stressed conditions via protein kinase C δ (PKCδ) activation. Furthermore, PKCδ-induced ERK1/2 activation by the inhibition of GSK-3 provoked the production of interleukin (IL)-10, playing a crucial role in regulating endotoxemia. Using a mitogen-activated protein kinase kinase-1 (MEK-1) and PKCδ inhibitor, we confirmed that GSK-3 inhibition induces PKCδ and subsequent ERK1/2 activation, resulting in increased IL-10 expression under LPS-treated conditions. We verified that septic shock caused by LPS is attenuated by GSK-3 inhibition using a GSK-3 inhibitor. This relieved endotoxemia induced by GSK-3 inhibition was restored in an ERK1/2-dependent manner. Taken together, IL-10 expression produced by GSK-3 inhibition-induced ERK1/2 activation via PKCδ relieved LPS-mediated endotoxemia. This finding suggests that IL-10 hyperexpression resulting from GSK-3 inhibition-induced ERK activation could be a new therapeutic pathway for endotoxemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1074/jbc.M111.308841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3340148PMC
April 2012

RG-II from Panax ginseng C.A. Meyer suppresses asthmatic reaction.

BMB Rep 2012 Feb;45(2):79-84

Department of Microbiology and Immunology, School of Medicine, Pusan National University, yangsan 626-770, Korea.

In asthma, T helper 2 (T(H)2)-type cytokines such as interleukin (IL)-4, IL-5, and IL-13 are produced by activated CD4(+) T cells. Dendritic cells played an important role in determining the fate of naive T cells into either T(H)1 or T(H)2 cells. We determined whether RG-II regulates the T(H)1/T(H)2 immune response by using an ovalbumin-induced murine model of asthma. RG-II reduced IL-4 production but increased interferon- gamma production, and inhibited GATA-3 gene expression. RG-II also inhibited asthmatic reactions including an increase in the number of eosinophils in bronchoalveolar lavage fluid, an increase in inflammatory cell infiltration in lung tissues, airway luminal narrowing, and airway hyperresponsiveness. This study provides evidence that RG-II plays a critical role in ameliorating the pathogenic process of asthmatic inflammation in mice. These findings provide new insights into the immunotherapeutic role of RG-II in terms of its effects in a murine model of asthma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5483/BMBRep.2012.45.2.79DOI Listing
February 2012

The Mycobacterium avium subsp. paratuberculosis fibronectin attachment protein, a toll-like receptor 4 agonist, enhances dendritic cell-based cancer vaccine potency.

Exp Mol Med 2012 May;44(5):340-9

Department of Microbiology and Immunology, School of Medicine, Pusan National University, Yangsan 626-870, Korea Research Institute of Convergence of Biomedical Science and Technology, Pusan National University, Yangsan 626-770, Korea.

In this study, we showed the direct interaction between Mycobacterium avium subsp. paratuberculosis fibronectin attachment protein (FAP) and toll-like receptor4 (TLR4) via co-localization and binding by using confocal microscopy and co-immunoprecipitation assays. FAP triggered the expression of pro- and antiinflammatory cytokines in a TLR4-dependent manner. In addition, FAP-induced cytokine expression in bone marrow-derived dendritic cells (BMDCs) was modulated in part by glycogen synthase kinase-3 (GSK-3). FAP-induced expression of CD80, CD86, major histocompatibility complex (MHC) class I, and MHC class II in TLR4(+/+) BMDCs was not observed in TLR4(-/-) BMDCs. Furthermore, FAP induced DC-mediated CD8(+) T cell proliferation and cytotoxic T lymphocyte (CTL) activity, and suppressed tumor growth with DC-based tumor vaccination in EG7 thymoma murine model. Taken together, these results indicate that the TLR4 agonist, FAP, a potential immunoadjuvant for DC-based cancer vaccination, improves the DC-based immune response via the TLR4 signaling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3858/emm.2012.44.5.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3366327PMC
May 2012

Novel modular endo-β-1,4-xylanase with transglycosylation activity from Cellulosimicrobium sp. strain HY-13 that is homologous to inverting GH family 6 enzymes.

Bioresour Technol 2012 Mar 27;107:25-32. Epub 2011 Dec 27.

Industrial Bio-materials Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-806, Republic of Korea.

The gene (2304-bp) encoding a novel xylanolytic enzyme (XylK2) with a catalytic domain, which is 70% identical to that of Cellulomonas flavigena DSM 20109 GH6 β-1,4-cellobiohydrolase, was identified from an earthworm (Eisenia fetida)-symbiotic bacterium, Cellulosimicrobium sp. strain HY-13. The enzyme consisted of an N-terminal catalytic GH6-like domain, a fibronectin type 3 (Fn3) domain, and a C-terminal carbohydrate-binding module 2 (CBM 2). XylK2ΔFn3-CBM 2 displayed high transferase activity (788.3 IU mg(-1)) toward p-nitrophenyl (PNP) cellobioside, but did not degrade xylobiose, glucose-based materials, or other PNP-sugar derivatives. Birchwood xylan was degraded by XylK2ΔFn3-CBM 2 to xylobiose (59.2%) and xylotriose (40.8%). The transglycosylation activity of the enzyme, which enabled the formation of xylobiose (33.6%) and xylotriose (66.4%) from the hydrolysis of xylotriose, indicates that it is not an inverting enzyme but a retaining enzyme. The endo-β-1,4-xylanase activity of XylK2ΔFn3-CBM 2 increased significantly by approximately 2.0-fold in the presence of 50mM xylobiose.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biortech.2011.12.106DOI Listing
March 2012

A highly active endo-β-1,4-mannanase produced by Cellulosimicrobium sp. strain HY-13, a hemicellulolytic bacterium in the gut of Eisenia fetida.

Enzyme Microb Technol 2011 Apr 12;48(4-5):365-70. Epub 2011 Jan 12.

Industrial Bio-materials Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-806, Republic of Korea.

A xylanolytic gut bacterium isolated from Eisenia fetida, Cellulosimicrobium sp. strain HY-13, produced an extracellular glycoside hydrolase capable of efficiently degrading mannose-based substrates such as locust bean gum, guar gum, mannotetraose, and mannopentaose. The purified mannan-degrading enzyme (ManK, 34,926 Da) from strain HY-13 was found to have an N-terminal amino acid sequence of DEATTDGLHVVDD, which has not yet been identified. Under the optimized reaction conditions of 50°C and pH 7.0, ManK exhibited extraordinary high specific activities of 7109 IU/mg and 5158 IU/mg toward locust bean gum and guar gum, respectively, while the enzyme showed no effect on sugars substituted with p-nitrophenol and various non-mannose carbohydrates. Thin layer chromatography revealed that the enzyme degraded locust bean gum to mannobiose and mannotetraose. No detectable amount of mannose was produced from hydrolytic reactions with the substrates. ManK strongly attached to Avicel, β-cyclodextrin, lignin, and poly(3-hydroxybutyrate) granules, but not bound to chitin, chitosan, curdlan, or insoluble oat spelt xylan. The aforementioned characteristics of ManK suggest that it is a unique endo-β-1,4-mannanase without additional carbohydrolase activities, which differentiates it from other well-known carbohydrolases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.enzmictec.2010.12.013DOI Listing
April 2011

Cosmomycin C inhibits signal transducer and activator of transcription 3 (STAT3) pathways in MDA-MB-468 breast cancer cell.

Bioorg Med Chem 2011 Dec 17;19(24):7582-9. Epub 2011 Oct 17.

Laboratory of Chemical Biology and Genomics, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahakro, Yoosung, Daejeon 305-806, Republic of Korea.

The signal transducer and activator of transcription 3 (STAT3) is constitutively activated in cancer cells. Therefore, blocking the aberrant activity of STAT3 in tumor cells is a validated therapeutic strategy. To discover novel inhibitors of STAT3 activity, we screened against microbial natural products using a dual-luciferase assay. Using the microbial metabolome library, we identified cosmomycin C (CosC), which was isolated from the mycelium extract of Streptomyces sp. KCTC19769, as a STAT3 pathway inhibitor. CosC inhibited STAT3 (Tyr705) phosphorylation and subsequent nuclear translocation in MDA-MB-468 breast cancer cells. CosC-mediated inhibition of STAT3 signaling pathway was confirmed by suppressed expression of STAT3 downstream target proteins including cyclin D1, Bcl-xL, survivin, Mcl-1, and VEGF in CosC-treated MDA-MB-468 cells. Flow cytometry showed that CosC caused accumulation in the G(0)-G(1) phase of the cell cycle and induced apoptosis via PARP cleavage and caspase-3 activation. Based on these findings, CosC may be a potential candidate for modulation of STAT3 pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmc.2011.10.025DOI Listing
December 2011

Mycobacterium tuberculosislpdC, Rv0462, induces dendritic cell maturation and Th1 polarization.

Biochem Biophys Res Commun 2011 Aug 18;411(3):642-7. Epub 2011 Jul 18.

Department of Microbiology and Immunology, School of Medicine, Pusan National University, Beom-eo Ri, Mulgum Eop, Yangsan, Gyeongsangnam-do 626-770, South Korea.

Mycobacterium tuberculosis, the etiological factor of pulmonary tuberculosis, causes significant morbidity and mortality worldwide. Activation of host immune responses for containment of mycobacterial infections involves participation of innate immune cells, such as dendritic cells (DCs). In this study, we demonstrated that the gene encoding lipoamide dehydrogenase C (lpdC) from M. tuberculosis, Rv0462, induce maturation and activation of DCs involved in the MAPKs signaling pathway. Moreover, Rv0462-treated DCs activated naïve T cells, polarized CD4(+) and CD8(+) T cells to secrete IFN-γ in syngeneic mixed lymphocyte reactions, which would be expected to contribute to Th1 polarization of the immune response. Our results suggest that Rv0462 can contribute to the innate and adaptive immune responses during tuberculosis infection, and thus modulate the clinical course of tuberculosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2011.07.013DOI Listing
August 2011

Cloning and characterization of a modular GH5 β-1,4-mannanase with high specific activity from the fibrolytic bacterium Cellulosimicrobium sp. strain HY-13.

Bioresour Technol 2011 Oct 28;102(19):9185-92. Epub 2011 Jun 28.

Industrial Bio-materials Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-806, Republic of Korea.

The gene (1272-bp) encoding a β-1,4-mannanase from a gut bacterium of Eisenia fetida, Cellulosimicrobium sp. strain HY-13 was cloned and expressed in Escherichia coli. The recombinant β-1,4-mannanase (rManH) was approximately 44.0 kDa and has a catalytic GH5 domain that is 65% identical to that of the Micromonospora sp. β-1,4-mannosidase. The enzyme exhibited the highest catalytic activity toward mannans at 50 °C and pH 6.0. rManH displayed a high specific activity of 14,711 and 8498 IU mg⁻¹ towards ivory nut mannan and locust bean gum, respectively; however it could not degrade the structurally unrelated polysaccharides, mannobiose, or p-nitrophenyl sugar derivatives. rManH was strongly bound to ivory nut mannan, Avicel, chitosan, and chitin but did not attach to curdlan, insoluble oat spelt xylan, lignin, or poly(3-hydroxybutyrate). The superior biocatalytic properties of rManH suggest that the enzyme can be exploited as an effective additive in the animal feed industry.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biortech.2011.06.073DOI Listing
October 2011

Venlafaxine inhibits the development and differentiation of dendritic cells through the regulation of P-glycoprotein.

Int Immunopharmacol 2011 Sep 23;11(9):1348-57. Epub 2011 May 23.

Department of Biology, College of Natural Science, Chosun University, Gwangju 501-759, South Korea.

Dendritic cells (DC) are professional antigen-presenting cells that have the ability to detect infectious materials; antigens to T lymphocytes, and serve as a bridge between innate and adaptive immunities. DC express the ATP-binding cassette transporters P-glycoprotein (P-gp). P-gp is a 170-kDa transmembrane protein encoded by the mdr-1 gene, a member of highly conserved superfamily of ATP-binding cassette transport proteins. Functionally, P-gp transporters have been described to be required for efficient DC and T cell migration. We report for the first time, at the best of our knowledge, P-gp is also required for DC development and differentiation in mouse bone marrow-derived DC. In this study, we found that an mdr-1 gene and P-gp protein level was increased during DC development and LPS-induced maturation. Moreover, the activity of P-gp was increased LPS-induced DC maturation. Next, we have attempted to determine whether the modulation of P-gp regulates surface molecules expression and cytokine production in DC. Specifically, down-regulation of P-gp by Venlafaxine (VLX) inhibits the differentiation of DC and cytokine production, such as IL-1, IL-10, and IL-12 during DC maturation. Moreover, the P-gp-decreased DC by VLX was displayed impaired induction of T cell polarizations, proliferation, and cytokine production, including IFN-γ, IL-4, and IL-2. Taken together, these findings also broaden current perspective concerning our understanding of the immunopharmacological functions of VLX and the development of therapeutic adjuvants for the treatment of DC-related acute and chronic diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.intimp.2011.04.019DOI Listing
September 2011

Deoxypodophyllotoxin Induces a Th1 Response and Enhances the Antitumor Efficacy of a Dendritic Cell-based Vaccine.

Immune Netw 2011 Feb 28;11(1):79-94. Epub 2011 Feb 28.

Department of Biology, College of Natural Sciences, Chosun University, Gwangju 501-759, Korea.

Background: Dendritic cell (DC)-based vaccines are currently being evaluated as a novel strategy for tumor vaccination and immunotherapy. However, inducing long-term regression in established tumor-implanted mice is difficult. Here, we show that deoxypohophyllotoxin (DPT) induces maturation and activation of bone marrow-derived DCs via Toll-like receptor (TLR) 4 activation of MAPK and NF-κB.

Methods: The phenotypic and functional maturation of DPT-treated DCs was assessed by flow cytometric analysis and cytokine production, respectively. DPT-treated DCs was also used for mixed leukocyte reaction to evaluate T cell-priming capacity and for tumor regression against melanoma.

Results: DPT promoted the activation of CD8(+) T cells and the Th1 immune response by inducing IL-12 production in DCs. In a B16F10 melanoma-implanted mouse model, we demonstrated that DPT-treated DCs (DPT-DCs) enhance immune priming and regression of an established tumor in vivo. Furthermore, migration of DPT-DCs to the draining lymph nodes was induced via CCR7 upregulation. Mice that received DPT-DCs displayed enhanced antitumor therapeutic efficacy, which was associated with increased IFN-γ production and induction of cytotoxic T lymphocyte activity.

Conclusion: These findings strongly suggest that the adjuvant effect of DPT in DC vaccination is associated with the polarization of T effector cells toward a Th1 phenotype and provides a potential therapeutic antitumor immunity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4110/in.2011.11.1.79DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3072678PMC
February 2011

Novel intracellular GH10 xylanase from Cohnella laeviribosi HY-21: biocatalytic properties and alterations of substrate specificities by site-directed mutagenesis of Trp residues.

Bioresour Technol 2010 Nov 7;101(22):8814-21. Epub 2010 Jul 7.

Industrial Bio-materials Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea.

The novel intracellular GH10 xylanase (iXylC) gene (1023-bp) of Cohnella laeviribosi HY-21 encoded a protein consisting of 340 amino acids with a deduced molecular mass of 39,330Da and a calculated pI of 5.81. The primary structure of iXylC was 70% identical to that of Geobacillus sp. GH10 enzyme (GenBank accession number: EDV78425). Xylanolytic activity of the His-tagged iXylC overproduced in Escherichiacoli BL21 was stimulated by 2.2-fold in the presence of 0.5% non-ionic detergents. iXylC produced a mixture of xylooligosaccharides (xylobiose to xylooctaose) from xylotriose and xylotetraose used as the hydrolytic substrate. In addition, it exhibited considerable cleavage activities for p-nitrophenylxylopyranoside (PNP-xylopyranoside) and PNP-cellobioside, indicating that iXylC is a unique GH10 enzyme. The hydrolytic activity (57.8IUmL(-1)) of iXylC toward PNP-xylopyranoside increased to 8.3-fold by W217A and W315A mutations, while mutations of W133A, W295A, and W303A abolished the hydrolytic activity of the enzyme.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biortech.2010.06.023DOI Listing
November 2010

Induction of indoleamine 2,3-dioxygenase expression via heme oxygenase-1-dependant pathway during murine dendritic cell maturation.

Biochem Pharmacol 2010 Aug 27;80(4):491-505. Epub 2010 Apr 27.

Department of Microbiology, Pusan National University, Beom-eo Ri, Mulgum Eop, Yangsan, Gyeongsangnam-do, South Korea.

Heme oxygenase (HO)-1 is expressed in a variety of conditions involved in the regulation of immune responses. In this study, we examined the role of HO-1 in dendritic cell (DC) maturation and expression of indoleamine 2,3-dioxygenase (IDO), a key enzyme that catalyzes the initial, rate-limiting step in tryptophan degradation. IDO deficiency led to diminished phenotypic and functional maturation of DCs in vitro and in vivo. IDO expression and DC maturation was abrogated by the HO inhibitor zinc protoporphrin, but increased by hemin, a potent inducer of HO-1. Moreover, LPS-induced HO-1 expression was mediated by an NF-kappaB-dependent pathway. Our findings provide additional insight into the immunological functions of IDO and HO-1, and suggest possible therapeutic adjuvants for the treatment of DC-related acute and chronic diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bcp.2010.04.025DOI Listing
August 2010

Novel GH10 xylanase, with a fibronectin type 3 domain, from Cellulosimicrobium sp. strain HY-13, a bacterium in the gut of Eisenia fetida.

Appl Environ Microbiol 2009 Nov 18;75(22):7275-9. Epub 2009 Sep 18.

Industrial Bio-Materials Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, South Korea

The gene encoding a novel modular xylanase from Cellulosimicrobium sp. strain HY-13 was identified and expressed in Escherichia coli, and its truncated gene product was characterized. The enzyme consisted of three distinct functional domains, an N-terminal catalytic GH10 domain, a fibronectin type 3 domain, and C-terminal carbohydrate-binding module 2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/AEM.01075-09DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2786537PMC
November 2009

Isolation of Sorangium cellulosum carrying epothilone gene clusters.

J Microbiol Biotechnol 2008 Aug;18(8):1416-22

Myxobacteria Bank, Department of Biotechnology, Hoseo University, Asan 336-795, Korea.

Epothilone and its analogs are a potent new class of anticancer compounds produced by myxobacteria. Thus, in an effort to identify new myxobacterial strains producing epothilone and its analogs, cellulose-degrading myxobacteria were isolated from Korean soils, and 13 strains carrying epothilone biosynthetic gene homologs were screened using a polymerase chain reaction. A migration assay revealed that Sorangium cellulosum KYC3013, 3016, 3017, and 3018 all produced microtubule-stabilizing compounds, and an LCMS/ MS analysis showed that S. cellulosum KYC3013 synthesized epothilone A.
View Article and Find Full Text PDF

Download full-text PDF

Source
August 2008

Hepatoprotective effect of Arazyme on CCl4-induced acute hepatic injury in SMP30 knock-out mice.

Toxicology 2008 Apr 19;246(2-3):132-42. Epub 2008 Jan 19.

Department of Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea.

Arazyme is a novel protease produced by the HY-3 strain of Aranicola proteolyticus, which is a Gram-negative aerobic bacterium that has been isolated from the intestine of the spider Nephila clavata. This study focused on the hepatoprotective effect of Arazyme on carbon tetrachloride (CCl4)-induced acute hepatic injury in senescence marker protein 30 (SMP30) knock-out (KO) mice and SMP30 wild-type (WT) mice. WT mice and SMP30 KO mice were divided into eight groups as follows: (i) two negative control groups (G1, G5) which were treated with a single intraperitoneal (i.p.) olive oil injection. (ii) Two positive control groups (G2, G6) which received a single i.p. CCl4 (0.4mL/kg) injection. (iii) Two vitamin C-treated groups (G3, G7) which received a single oral administration of vitamin C (100mg/kg) and were injected with a single i.p. CCl4 (0.4mL/kg). (iv) Two Arazyme-treated groups (G4, G8) which received a single oral administration of Arazyme (500mg/kg) and were injected with a single i.p. CCl4 (0.4mL/kg). Through present study, we could find that Arazyme-treated groups showed decreased degree of liver injury, increased expression of SMP30, decreased expression of phospho-Smad3 (p-Smad3), elevated expression of antioxidant proteins including sorbitol dehydrogenase, dihydropteridine reductase (DHPR), dehydrofolate reductase (DHFR), NADH dehydrogenase, glutathione S-transferase kappa 1 (GSTK1) and phospholipid hydroperoxide glutathione peroxidase (PHGPx) compared with non-Arazyme-treated groups. Therefore, it is concluded that Arazyme plays a significant role in protecting injured hepatocytes by increasing the expression of SMP30, inhibiting the transforming growth factor-beta (TGF-beta)/Smad pathway and elevating the expression of antioxidant proteins.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tox.2008.01.006DOI Listing
April 2008

Biochemical and genetic characterization of arazyme, an extracellular metalloprotease produced from Serratia proteamaculans HY-3.

J Microbiol Biotechnol 2007 May;17(5):761-8

Insect Resources Research Center Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Korea Insect BioTech Co., Ltd., Daejeon 305-811, Korea.

Serratia proteamaculans HY-3 isolated from the digestive tract of a spider produces an extracellular protease named arazyme, with an estimated molecular mass of 51.5 kDa. The purified enzyme was characterized as having high activities at wide pH and temperature ranges. We further characterized biochemical features of the enzymatic reactions under various reaction conditions. The protease efficiently hydrolyzed a broad range of protein substrates including albumin, keratin, and collagen. The dependence of enzymatic activities on the presence of metal ions such as calcium and zinc indicated that the enzyme is a metalloprotease, together with the previous observation that the proteolytic activity of the enzyme was not inhibited by aspartate, cysteine, or serine protease inhibitors, but strongly inhibited by 1,10-phenanthroline and EDTA. The araA gene encoding the exoprotease was isolated as a 5.6 kb BamHl fragment after PCR amplification using degenerate primers and subsequent Southern hybridization. The nucleotide sequence revealed that the deduced amino acid sequences shared extensive similarity with those of the serralysin family of metalloproteases from other enteric bacteria. A gene (inh) encoding a putative protease inhibitor was also identified immediately adjacent to the araA structural gene.
View Article and Find Full Text PDF

Download full-text PDF

Source
May 2007

KRIBB3, a novel microtubule inhibitor, induces mitotic arrest and apoptosis in human cancer cells.

Biochem Pharmacol 2008 Jan 30;75(2):383-94. Epub 2007 Aug 30.

Molecular Cancer Research Center, Korea Research Institute of Bioscience and Biotechnology, 52 Eoeun-dong Yuseong-gu, Daejeon 305-806, Republic of Korea.

KRIBB3 (5-(5-ethyl-2-hydroxy-4-methoxyphenyl)-4-(4-methoxyphenyl) isoxazole) inhibited cancer cell growth in vitro and in vivo. Flow cytometry studies showed that KRIBB3 caused cell cycle arrest at the G(2)/M phase and subsequent apoptosis. This was confirmed as accumulation of Cyclin B1 and cleavage of poly(ADP-ribose) polymerase (PARP) were detected. While transient inhibition by KRIBB3 led to reversible mitotic arrest, prolonged exposure to KRIBB3-induced apoptosis. Co-immunoprecipitation experiments showed that KRIBB3 initially induced association of inhibitory Mad2 with p55CDC (mammalian homologue of CDC20), an activator of APC/C (anaphase-promoting complex/cyclosome), suggesting that the mitotic spindle checkpoint was activated by KRIBB3. However, the level of this inhibitory complex of Mad2 with p55CDC was gradually decreased 24 h after KRIBB3 treatment, and was hardly detectable after 48 h, indicating some slipping of the mitotic checkpoint. Consistent with these observations, KRIBB3 activated the mitotic spindle checkpoint by disrupting the microtubule cytoskeleton. KRIBB3 was proven to be a tubulin inhibitor using in vitro polymerization assays and in vivo indirect immunofluorescence staining. The temporal pattern of Bax activation by KRIBB3 was similar to PARP cleavage, suggesting that Bax is a mediator of KRIBB3-dependent apoptosis. Furthermore, when KRIBB3 was administered intraperitoneally into nude mice at 50 mg/kg or 100 mg/kg, it inhibited 49.5 or 70.3% of tumor growth, respectively. These results suggest that KRIBB3 is a good drug candidate for cancer therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bcp.2007.08.027DOI Listing
January 2008

Synthesis and biological evaluation of cinnamyl compounds as potent antitumor agents.

Bioorg Med Chem Lett 2007 Oct 25;17(19):5423-7. Epub 2007 Jul 25.

Korea Research Institute of Bioscience and Biotechnology, 52 Uendong Yoosung, Daejeon 305-333, Republic of Korea.

A series of cinnamyl compounds related to 2'-hydroxycinnamaldehyde were synthesized and their antitumor effects against human cancer cells evaluated. Hydroxylamine derivative 6 inhibited the growth of human cancer cells and human colon tumor xenograft in nude mice. Its antitumor effects belong to the induction of apoptosis and arresting cell cycle at G(2)/M phase, which is confirmed by detection of apoptosis markers and cell cycle analysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmcl.2007.07.033DOI Listing
October 2007

Apoptosis induction of 2'-hydroxycinnamaldehyde as a proteasome inhibitor is associated with ER stress and mitochondrial perturbation in cancer cells.

Biochem Pharmacol 2007 Aug 24;74(4):557-65. Epub 2007 May 24.

Department of Dental Microbiology, School of Dentistry, Kyungpook National University, Daegu 700-412, Republic of Korea.

2'-Hydroxycinnamaldehyde (HCA), isolated from the stem bark of Cinnamomum cassia, and 2'-benzoyloxycinnamaldehyde (BCA), one of HCA derivatives, have antiproliferative activities on several human cancer cell lines. Our previous study suggested that reactive oxygen species (ROS) and caspase-3 are the major regulators of HCA-induced apoptosis. In the present study, we demonstrated a novel molecular target using in vitro pull-down assay by biotin-labeled HCA (biotin-HCA) in SW620 cells. We analyzed 11 differential spots of 2-dimensional gel prepared with pull-downed proteins by biotin-HCA. Among them, five spots were identified as proteasome subunits. An in vitro 26S proteasome function assay using specific fluorogenic substrates showed that HCA potently inhibits L3-like activity of the proteasome. In addition, HCA showed inhibitory action against chymotrypsin-like, trypsin-like, and PGPH-like activities. DNA microarray showed that HCA induced heat shock family and ER stress-responsive genes, which reflects the accumulation of misfolded proteins by proteasome inhibition. On western blot analysis, it was confirmed that HCA induces glucose-regulated protein, 78 kDa (GRP78) and some representative endoplasmic reticulum (ER) stress-responsive proteins. Furthermore, HCA treatment decreased mitochondrial membrane potential. The effect of HCA on cytochrome c and Bax translocation between cytosol and mitochondrial membrane was clarified using western blot analysis. These results suggest that HCA-induced apoptosis is associated with the inhibition of the proteasome activity that leads in turn to the increase of ER stress and mitochondrial perturbation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bcp.2007.05.016DOI Listing
August 2007

Anthraquinones, Cdc25B phosphatase inhibitors, isolated from the roots of Polygonum multiflorum Thunb.

Nat Prod Res 2007 May;21(6):487-93

Korea Research Institute of Bioscience and Biotechnology, University of Science and Technology in Korea, Yoosung-Gu, Daejeon, Republic of Korea.

Three anthraquinones, Cdc25B phosphatase inhibitors, were isolated from the methanolic extract of the roots of Polygonum multiflorum Thunb. (Polygonaceae). Anthraquinones, physcion (1), emodin (2), and questin (3), inhibited the enzymatic activity of Cdc25B phosphatase with IC(50) values of 62.5, 30, and 34 microg mL(-1), respectively. Emodin (2) and questin (3) strongly inhibited the growth of human colon cancer cells, SW620 with GI(50) values of 6.1 and 0.9 microg mL(-1), respectively. Commercially available anthraquinones, chrysophanol (4), and rhein (5) also inhibited Cdc25B phosphatase with IC(50) values of 10.7 and 22.1 microg mL(-1), respectively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14786410601012265DOI Listing
May 2007