NobleBlocks

Korea Basic Science Institute

facilityDaejeon, Daejeon, South Korea

Research output, citation impact, and the most-cited recent papers from Korea Basic Science Institute (South Korea). Aggregated across the NobleBlocks index of 300M+ scholarly works.

Total works
22.4K
Citations
629.7K
h-index
225
i10-index
12.6K
Also known as
Korea Basic Science Institute한국기초과학지원연구원

Top-cited papers from Korea Basic Science Institute

Rapid Detection of COVID-19 Causative Virus (SARS-CoV-2) in Human Nasopharyngeal Swab Specimens Using Field-Effect Transistor-Based Biosensor
Giwan Seo, Geonhee Lee, Mi Jeong Kim, Seung-Hwa Baek +4 more
2020· ACS Nano1.8Kdoi:10.1021/acsnano.0c02823

copies/mL). Thus, we have successfully fabricated a promising FET biosensor for SARS-CoV-2; our device is a highly sensitive immunological diagnostic method for COVID-19 that requires no sample pretreatment or labeling.

3D Macroporous Graphene Frameworks for Supercapacitors with High Energy and Power Densities
Bong Gill Choi, Min Yang, Won Hi Hong, Jang Wook Choi +1 more
2012· ACS Nano1.3Kdoi:10.1021/nn3003345

In order to develop energy storage devices with high power and energy densities, electrodes should hold well-defined pathways for efficient ionic and electronic transport. Herein, we demonstrate high-performance supercapacitors by building a three-dimensional (3D) macroporous structure that consists of chemically modified graphene (CMG). These 3D macroporous electrodes, namely, embossed-CMG (e-CMG) films, were fabricated by using polystyrene colloidal particles as a sacrificial template. Furthermore, for further capacitance boost, a thin layer of MnO(2) was additionally deposited onto e-CMG. The porous graphene structure with a large surface area facilitates fast ionic transport within the electrode while preserving decent electronic conductivity and thus endows MnO(2)/e-CMG composite electrodes with excellent electrochemical properties such as a specific capacitance of 389 F/g at 1 A/g and 97.7% capacitance retention upon a current increase to 35 A/g. Moreover, when the MnO(2)/e-CMG composite electrode was asymmetrically assembled with an e-CMG electrode, the assembled full cell shows remarkable cell performance: energy density of 44 Wh/kg, power density of 25 kW/kg, and excellent cycle life.

The <i>Amborella</i> Genome and the Evolution of Flowering Plants
Amborella Genome Project, Victor A. Albert, W. Brad Barbazuk, Claude W. dePamphilis +4 more
2013· Science908doi:10.1126/science.1241089

Amborella trichopoda is strongly supported as the single living species of the sister lineage to all other extant flowering plants, providing a unique reference for inferring the genome content and structure of the most recent common ancestor (MRCA) of living angiosperms. Sequencing the Amborella genome, we identified an ancient genome duplication predating angiosperm diversification, without evidence of subsequent, lineage-specific genome duplications. Comparisons between Amborella and other angiosperms facilitated reconstruction of the ancestral angiosperm gene content and gene order in the MRCA of core eudicots. We identify new gene families, gene duplications, and floral protein-protein interactions that first appeared in the ancestral angiosperm. Transposable elements in Amborella are ancient and highly divergent, with no recent transposon radiations. Population genomic analysis across Amborella's native range in New Caledonia reveals a recent genetic bottleneck and geographic structure with conservation implications.

Insect Gut Bacterial Diversity Determined by Environmental Habitat, Diet, Developmental Stage, and Phylogeny of Host
Ji‐Hyun Yun, Seong Woon Roh, Tae Woong Whon, Mi‐Ja Jung +4 more
2014· Applied and Environmental Microbiology844doi:10.1128/aem.01226-14

Insects are the most abundant animals on Earth, and the microbiota within their guts play important roles by engaging in beneficial and pathological interactions with these hosts. In this study, we comprehensively characterized insect-associated gut bacteria of 305 individuals belonging to 218 species in 21 taxonomic orders, using 454 pyrosequencing of 16S rRNA genes. In total, 174,374 sequence reads were obtained, identifying 9,301 bacterial operational taxonomic units (OTUs) at the 3% distance level from all samples, with an average of 84.3 (± 97.7) OTUs per sample. The insect gut microbiota were dominated by Proteobacteria (62.1% of the total reads, including 14.1% Wolbachia sequences) and Firmicutes (20.7%). Significant differences were found in the relative abundances of anaerobes in insects and were classified according to the criteria of host environmental habitat, diet, developmental stage, and phylogeny. Gut bacterial diversity was significantly higher in omnivorous insects than in stenophagous (carnivorous and herbivorous) insects. This insect-order-spanning investigation of the gut microbiota provides insights into the relationships between insects and their gut bacterial communities.

Coherent Two-Dimensional Optical Spectroscopy
Minhaeng Cho
2008· Chemical Reviews828doi:10.1021/cr078377b

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCoherent Two-Dimensional Optical SpectroscopyMinhaeng ChoView Author Information Department of Chemistry and Center for Multidimensional Spectroscopy, Korea University, Seoul 136-701, Korea, and Multidimensional Spectroscopy Laboratory, Korea Basic Science Institute, Seoul 136-713, Korea Cite this: Chem. Rev. 2008, 108, 4, 1331–1418Publication Date (Web):March 26, 2008Publication History Received16 October 2007Published online26 March 2008Published inissue 1 April 2008https://doi.org/10.1021/cr078377bCopyright © 2008 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views9997Altmetric-Citations677LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (6 MB) Get e-AlertscloseSUBJECTS:Amides,Infrared light,Infrared spectroscopy,Molecular structure,Peptides and proteins Get e-Alerts

Overview of the HUPO Plasma Proteome Project: Results from the pilot phase with 35 collaborating laboratories and multiple analytical groups, generating a core dataset of 3020 proteins and a publicly‐available database
Gilbert S. Omenn, David J. States, Marcin Adamski, Thomas W. Blackwell +4 more
2005· PROTEOMICS791doi:10.1002/pmic.200500358

HUPO initiated the Plasma Proteome Project (PPP) in 2002. Its pilot phase has (1) evaluated advantages and limitations of many depletion, fractionation, and MS technology platforms; (2) compared PPP reference specimens of human serum and EDTA, heparin, and citrate-anti-coagulated plasma; and (3) created a publicly-available knowledge base (www.bioinformatics.med.umich.edu/hupo/ppp; www.ebi.ac.uk/pride). Thirty-five participating laboratories in 13 countries submitted datasets. Working groups addressed (a) specimen stability and protein concentrations; (b) protein identifications from 18 MS/MS datasets; (c) independent analyses from raw MS-MS spectra; (d) search engine performance, subproteome analyses, and biological insights; (e) antibody arrays; and (f) direct MS/SELDI analyses. MS-MS datasets had 15 710 different International Protein Index (IPI) protein IDs; our integration algorithm applied to multiple matches of peptide sequences yielded 9504 IPI proteins identified with one or more peptides and 3020 proteins identified with two or more peptides (the Core Dataset). These proteins have been characterized with Gene Ontology, InterPro, Novartis Atlas, OMIM, and immunoassay-based concentration determinations. The database permits examination of many other subsets, such as 1274 proteins identified with three or more peptides. Reverse protein to DNA matching identified proteins for 118 previously unidentified ORFs. We recommend use of plasma instead of serum, with EDTA (or citrate) for anticoagulation. To improve resolution, sensitivity and reproducibility of peptide identifications and protein matches, we recommend combinations of depletion, fractionation, and MS/MS technologies, with explicit criteria for evaluation of spectra, use of search algorithms, and integration of homologous protein matches. This Special Issue of PROTEOMICS presents papers integral to the collaborative analysis plus many reports of supplementary work on various aspects of the PPP workplan. These PPP results on complexity, dynamic range, incomplete sampling, false-positive matches, and integration of diverse datasets for plasma and serum proteins lay a foundation for development and validation of circulating protein biomarkers in health and disease.

Study of diluted magnetic semiconductor: Co-doped ZnO
Hyunjun Lee, Se‐Young Jeong, Chae‐Ryong Cho, Chul‐Hong Park
2002· Applied Physics Letters668doi:10.1063/1.1517405

We report on the high-temperature ferromagnetism in Co-doped ZnO films fabricated by the sol–gel method above 350 K. The lattice constant of c axis of wurtzite Zn1−xCoxO follows Vergard’s law for 0&amp;lt;x&amp;lt;0.25. For Zn1−xCoxO with x⩾0.25, a secondary phase is detected. The Zn1−xCoxO exhibits ferromagnetic behavior with a Curie temperature higher than 350 K. By the results of x-ray photoelectron spectroscopy measurement, we assume that Co occupied the Zn site without changing the wurtzite structure. In the case of x=0.2, the coercive field measured by a magnetization–magnetic field hysteresis curve at 350 K was nearly 80 Oe. Additionally, we investigated the electric structure through first-principles pseudopotential plane-wave calculation.

Conductive 2D metal-organic framework for high-performance cathodes in aqueous rechargeable zinc batteries
Kwan Woo Nam, Sarah S. Park, Roberto dos Reis, Vinayak P. Dravid +3 more
2019· Nature Communications664doi:10.1038/s41467-019-12857-4

Abstract Currently, there is considerable interest in developing advanced rechargeable batteries that boast efficient distribution of electricity and economic feasibility for use in large-scale energy storage systems. Rechargeable aqueous zinc batteries are promising alternatives to lithium-ion batteries in terms of rate performance, cost, and safety. In this investigation, we employ Cu 3 (HHTP) 2 , a two-dimensional (2D) conductive metal-organic framework (MOF) with large one-dimensional channels, as a zinc battery cathode. Owing to its unique structure, hydrated Zn 2+ ions which are inserted directly into the host structure, Cu 3 (HHTP) 2 , allow high diffusion rate and low interfacial resistance which enable the Cu 3 (HHTP) 2 cathode to follow the intercalation pseudocapacitance mechanism. Cu 3 (HHTP) 2 exhibits a high reversible capacity of 228 mAh g −1 at 50 mA g −1 . At a high current density of 4000 mA g −1 (~18 C), 75.0% of the initial capacity is maintained after 500 cycles. These results provide key insights into high-performance, 2D conductive MOF designs for battery electrodes.

Toxicity and bioavailability of copper nanoparticles to the terrestrial plants mung bean (<i>Phaseolus radiatus</i>) and wheat (<i>Triticum aestivum</i>): Plant agar test for water-insoluble nanoparticles
Woo-Mi Lee, Youn‐Joo An, Hye-On Yoon, Hee‐Seok Kweon
2008· Environmental Toxicology and Chemistry645doi:10.1897/07-481.1

Because of their insolubility in water, nanoparticles have a limitation concerning toxicity experiments. The present study demonstrated a plant agar test for homogeneous exposure of nanoparticles to plant species. The effect of Cu nanoparticles on the growth of a plant seedling was studied, and bioaccumulation of nanoparticles was investigated. All tests were conducted in plant agar media to prevent precipitation of water-insoluble nanoparticles in test units. The plant species were Phaseolus radiatus (mung bean) and Triticum aestivum (wheat). Growth inhibition of a seedling exposed to different concentrations of Cu nanoparticles was examined. Copper nanoparticles were toxic to both plants and also were bioavailable. The 2-d median effective concentrations for P. radiatus and T. aestivum exposed to Cu nanoparticles were 335 (95% confidence level, 251-447) and 570 (450-722) mg/L, respectively. Phaseolus radiatus was more sensitive than T. aestivum to Cu nanoparticles. A cupric ion released from Cu nanoparticles had negligible effects in the concentration ranges of the present study, and the apparent toxicity clearly resulted from Cu nanoparticles. Bioaccumulation increased with increasing concentration of Cu nanoparticles, and agglomeration of particles was observed in the cells using transmission-electron microscopy-energy-dispersive spectroscopy. The present study demonstrated that the plant agar test was a good protocol for testing the phytotoxicity of nanoparticles, which are hardly water soluble.

Co-metal clustering as the origin of ferromagnetism in Co-doped ZnO thin films
Jung H. Park, Min Gyu Kim, Hyun M. Jang, Sangwoo Ryu +1 more
2004· Applied Physics Letters621doi:10.1063/1.1650915

The origin of ferromagnetism in ZnO-based systems was investigated using Co-doped ZnO thin films as prototypical examples of II–VI-based diluted magnetic semiconductors. In spite of the atomic-scale dissolution of Co ions in wurtzite ZnO, both the magnetization-temperature curve and the magnetization-field curve demonstrated that Zn1−xCoxO thin films were paramagnetic for x⩽0.12. On the other hand, Zn1−xCoxO films with x greater than 0.12 were characterized by the Co-metal clustering and apparently showed room-temperature ferromagnetism. The discrepancy between the zero-field cooling and the field cooling curves further indicates that Co-doped ZnO films (for x&amp;gt;0.12) are superparamagnetic and the observed ferromagnetism originates from the nanometer-sized Co clusters.

Human eye-inspired soft optoelectronic device using high-density MoS2-graphene curved image sensor array
Changsoon Choi, Moon Kee Choi, Siyi Liu, Minsung Kim +4 more
2017· Nature Communications531doi:10.1038/s41467-017-01824-6

Abstract Soft bioelectronic devices provide new opportunities for next-generation implantable devices owing to their soft mechanical nature that leads to minimal tissue damages and immune responses. However, a soft form of the implantable optoelectronic device for optical sensing and retinal stimulation has not been developed yet because of the bulkiness and rigidity of conventional imaging modules and their composing materials. Here, we describe a high-density and hemispherically curved image sensor array that leverages the atomically thin MoS 2 -graphene heterostructure and strain-releasing device designs. The hemispherically curved image sensor array exhibits infrared blindness and successfully acquires pixelated optical signals. We corroborate the validity of the proposed soft materials and ultrathin device designs through theoretical modeling and finite element analysis. Then, we propose the ultrathin hemispherically curved image sensor array as a promising imaging element in the soft retinal implant. The CurvIS array is applied as a human eye-inspired soft implantable optoelectronic device that can detect optical signals and apply programmed electrical stimulation to optic nerves with minimum mechanical side effects to the retina.

Microporous Carbon Nanoplates from Regenerated Silk Proteins for Supercapacitors
Young Soo Yun, Se Youn Cho, Jinyong Shim, Byung Hoon Kim +4 more
2013· Advanced Materials521doi:10.1002/adma.201204692

Novel carbon-based microporous nanoplates containing numerous heteroatoms (H-CMNs) are fabricated from regenerated silk fibroin by the carbonization and activation of KOH. The H-CMNs exhibit superior electrochemical performance, displaying a specific capacitance of 264 F/g in aqueous electrolytes, a specific energy of 133 Wh/kg, a specific power of 217 kW/kg, and a stable cycle life over 10000 cycles. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Photoluminescent Green Carbon Nanodots from Food-Waste-Derived Sources: Large-Scale Synthesis, Properties, and Biomedical Applications
So‐Young Park, Hyun Uk Lee, Eun Sik Park, Soon Chang Lee +4 more
2014· ACS Applied Materials & Interfaces516doi:10.1021/am500159p

We have developed a simple approach for the large-scale synthesis of water-soluble green carbon nanodots (G-dots) from many kinds of large food waste-derived sources. About 120 g of G-dots per 100 kg of food waste can be synthesized using our simple and environmentally friendly synthesis approach. The G-dots exhibit a high degree of solubility in water because of the abundant oxygen-containing functional groups around their surface. The narrow band of photoluminescence emission (400-470 nm) confirms that the size of the G-dots (∼4 nm) is small because of a similar quantum effects and emission traps on the surfaces. The G-dots have excellent photostability; their photoluminescence intensity decreases slowly (∼8%) under continuous excitation with a Xe lamp for 10 days. We carried out cell viability assay to assess the effect of cytotoxicity by introducing G-dots in cells such as Chinese hamster ovary cells (CHO-K1), mouse muscle cells (C2C12), and African green monkey kidney cells (COS-7), up to a concentration of 2 mg mL(-1) for 24 h. Due to their high photostability and low cytotoxicity, these G-dots are excellent probes for in vitro bioimaging. Moreover, the byproducts (not including G-dots) of G-dot synthesis from large food-waste derived sources promoted the growth and development of seedlings germinated on 3DW-supplemented gauze. Because of the combined advantages of green synthesis, high aqueous stability, high photostability, and low cytotoxicity, the G-dots show considerable promise in various areas, including biomedical imaging, solution state optoelectronics, and plant seed germination and/or growth.

H3K4 mono- and di-methyltransferase MLL4 is required for enhancer activation during cell differentiation
Ji‐Eun Lee, Chaochen Wang, Shiliyang Xu, Young‐Wook Cho +4 more
2013· eLife511doi:10.7554/elife.01503

Enhancers play a central role in cell-type-specific gene expression and are marked by H3K4me1/2. Active enhancers are further marked by H3K27ac. However, the methyltransferases responsible for H3K4me1/2 on enhancers remain elusive. Furthermore, how these enzymes function on enhancers to regulate cell-type-specific gene expression is unclear. In this study, we identify MLL4 (KMT2D) as a major mammalian H3K4 mono- and di-methyltransferase with partial functional redundancy with MLL3 (KMT2C). Using adipogenesis and myogenesis as model systems, we show that MLL4 exhibits cell-type- and differentiation-stage-specific genomic binding and is predominantly localized on enhancers. MLL4 co-localizes with lineage-determining transcription factors (TFs) on active enhancers during differentiation. Deletion of Mll4 markedly decreases H3K4me1/2, H3K27ac, Mediator and Polymerase II levels on enhancers and leads to severe defects in cell-type-specific gene expression and cell differentiation. Together, these findings identify MLL4 as a major mammalian H3K4 mono- and di-methyltransferase essential for enhancer activation during cell differentiation. DOI: http://dx.doi.org/10.7554/eLife.01503.001.

Size‐Dependent Magnetic Properties of Colloidal Mn<sub>3</sub>O<sub>4</sub> and MnO Nanoparticles
Won Seok Seo, Hyong Hoon Jo, Kwangyeol Lee, Bongsoo Kim +2 more
2004· Angewandte Chemie International Edition505doi:10.1002/anie.200352400

Highly crystalline and monodisperse MnO and Mn3O4 nanoparticles are prepared by thermal decomposition of [Mn(acac)2] in oleylamine under an inert atmosphere in the presence and absence of a small amount of water, respectively (see picture). The particle size of both manganese oxide systems can be easily manipulated by changing the employed reaction temperature, and it has been demonstrated that the magnetic behavior depends on the size of the particles. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2004/z52400_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Overcoming Artifacts from Metallic Orthopedic Implants at High-Field-Strength MR Imaging and Multi-detector CT
Mi‐Jung Lee, Sung Jun Kim, Sung-Ah Lee, Ho‐Taek Song +4 more
2007· Radiographics504doi:10.1148/rg.273065087

At magnetic resonance (MR) imaging and multidetector computed tomography (CT), artifacts arising from metallic orthopedic hardware are an obstacle to obtaining optimal images. Although various techniques for reducing such artifacts have been developed and corroborated by previous researchers, a new era of more powerful MR imaging and multidetector CT modalities has renewed the importance of a systematic consideration of methods for artifact reduction. Knowledge of the factors that contribute to artifacts, of related theories, and of artifact reduction techniques has become mandatory for radiologists. Factors that affect artifacts on MR images include the composition of the metallic hardware, the orientation of the hardware in relation to the direction of the main magnetic field, the strength of the magnetic field, the pulse sequence type, and other MR imaging parameters (mainly voxel size, which is determined by the field of view, image matrix, section thickness, and echo train length). At multidetector CT, the factors that affect artifacts include the composition of the hardware, orientation of the hardware, acquisition parameters (peak voltage, tube charge, collimation, and acquired section thickness), and reconstruction parameters (reconstructed section thickness, reconstruction algorithm used, and whether an extended CT scale was used). A comparison of images obtained with different hardware and different acquisition and reconstruction parameters facilitates an understanding of methods for reducing or overcoming artifacts related to metallic implants.

Polyunsaturated fatty acid biosynthesis pathway determines ferroptosis sensitivity in gastric cancer
Ji-Yoon Lee, Miso Nam, Hye Young Son, Kwangbeom Hyun +4 more
2020· Proceedings of the National Academy of Sciences480doi:10.1073/pnas.2006828117

Ferroptosis is an iron-dependent regulated necrosis mediated by lipid peroxidation. Cancer cells survive under metabolic stress conditions by altering lipid metabolism, which may alter their sensitivity to ferroptosis. However, the association between lipid metabolism and ferroptosis is not completely understood. In this study, we found that the expression of elongation of very long-chain fatty acid protein 5 (ELOVL5) and fatty acid desaturase 1 (FADS1) is up-regulated in mesenchymal-type gastric cancer cells (GCs), leading to ferroptosis sensitization. In contrast, these enzymes are silenced by DNA methylation in intestinal-type GCs, rendering cells resistant to ferroptosis. Lipid profiling and isotope tracing analyses revealed that intestinal-type GCs are unable to generate arachidonic acid (AA) and adrenic acid (AdA) from linoleic acid. AA supplementation of intestinal-type GCs restores their sensitivity to ferroptosis. Based on these data, the polyunsaturated fatty acid (PUFA) biosynthesis pathway plays an essential role in ferroptosis; thus, this pathway potentially represents a marker for predicting the efficacy of ferroptosis-mediated cancer therapy.

Best practices for fNIRS publications
Meryem A. Yücel, Alexander von Lühmann, Felix Scholkmann, Judit Gervain +4 more
2021· Neurophotonics472doi:10.1117/1.nph.8.1.012101

The application of functional near-infrared spectroscopy (fNIRS) in the neurosciences has been expanding over the last 40 years. Today, it is addressing a wide range of applications within different populations and utilizes a great variety of experimental paradigms. With the rapid growth and the diversification of research methods, some inconsistencies are appearing in the way in which methods are presented, which can make the interpretation and replication of studies unnecessarily challenging. The Society for Functional Near-Infrared Spectroscopy has thus been motivated to organize a representative (but not exhaustive) group of leaders in the field to build a consensus on the best practices for describing the methods utilized in fNIRS studies. Our paper has been designed to provide guidelines to help enhance the reliability, repeatability, and traceability of reported fNIRS studies and encourage best practices throughout the community. A checklist is provided to guide authors in the preparation of their manuscripts and to assist reviewers when evaluating fNIRS papers.

A Self-Calibrating Bipartite Viscosity Sensor for Mitochondria
Zhigang Yang, Yanxia He, Jaehong Lee, Nayoung Park +4 more
2013· Journal of the American Chemical Society465doi:10.1021/ja403851p

A self-calibrating bipartite viscosity sensor 1 for cellular mitochondria, composed of coumarin and boron-dipyrromethene (BODIPY) with a rigid phenyl spacer and a mitochondria-targeting unit, was synthesized. The sensor showed a direct linear relationship between the fluorescence intensity ratio of BODIPY to coumarin or the fluorescence lifetime ratio and the media viscosity, which allowed us to determine the average mitochondrial viscosity in living HeLa cells as ca. 62 cP (cp). Upon treatment with an ionophore, monensin, or nystatin, the mitochondrial viscosity was observed to increase to ca. 110 cP.

Novel and therapeutic effect of caffeic acid and caffeic acid phenyl ester on hepatocarcinoma cells: complete regression of hepatoma growth and metastasis by dual mechanism
Tae‐Wook Chung, Sung‐Kwon Moon, Young‐Chae Chang, Jeong‐Heon Ko +4 more
2004· The FASEB Journal457doi:10.1096/fj.04-2126com

Our previous studies have clearly shown that the angiogenic enzymes, matrix metalloproteinase (MMP) -2/9, are directly involved in human hepatic tumorigenesis and metastasis and suggest that the MMP-2/9 inhibitors, which have dual inhibitory activities on enzyme activity and transcription, represent the best candidates for achieving tumor regression. Many anti-cancer drugs have strong cellular cytotoxicity and side effects, indicating that strong anti-cancer drugs that have no or minimal cytotoxicity and side effects need to be developed. The specific aim of the present study was to develop powerful anti-cancer drugs with specific tumor regression and anti-metastatic potential having the dual inhibitory activities of specific MMP-2 and -9 enzyme activities and gene transcription at the molecular level. Caffeic acid (CA), a strong and selective MMP-9 activity and transcription inhibitor, was isolated from the plant Euonymus alatus and its derivative, caffeic acid phenethyl ester (CAPE), was synthesized. CA and CAPE selectively inhibited MMP-2 and -9 but not -1, -3, -7, or cathepsin K. Treatment of HepG2 cells with CA (100 microg/mL) and CAPE (5 microg/mL) suppressed phorbol 12-myristate 13-acetate (PMA) -induced MMP-9 expression by inhibiting the function of NF-kappaB, but not AP-1. We confirmed that CA and CAPE suppressed the growth of HepG2 tumor xenografts in nude mice in vivo. The subcutaneous and oral administrations of CA and CAPE significantly reduced the liver metastasis. These results confirm the therapeutic potential of the compounds and suggest that the anti-metastatic and anti-tumor effects of CA and CAPE are mediated through the selective suppression of MMP-9 enzyme activity and transcriptional down-regulation by the dual inhibition of NF-kappaB as well as MMP-9 catalytic activity.