Yoongho Lim

Konkuk University, Sŏul, Seoul, South Korea

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Publications (165)383.11 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: The selective killing of tumor cells is an important strategy for cancer therapeutics. The aim of this study was to develop a novel antitumor agent that is safe for normal cells with the ability to selectively target cancer cells. Experimental Design: Based on quantitative structure-activity relationship, we synthesized a novel polyphenol conjugate, (E)-3-(3,5-dimethoxyphenyl)-1-(2-methoxyphenyl)prop-2-en-1-one (DPP-23). We evaluated the effect of DPP-23 on proliferation, cell cycle, and apoptosis in various tumor cells. We also assessed molecular targets of DPP-23 using genome-wide expression profiling by DNA microarray and real-time PCR array systems. Results: DPP-23 effectively inhibited the growth of cancer cells in vitro and in vivo (xenografts in Balb/c nude mice). At a molecular level, DPP-23 targeted the unfolded protein response (UPR) in the endoplasmic reticulum (ER) through the production of reactive-oxygen species (ROS) in cancer cells, but not in normal cells, resulting in selective killing of tumor cells via caspase-dependent apoptosis. Conclusions: The selective generation of ROS in cancer cells could be an attractive strategy for the selective killing of cancer cells, while maintaining negligible cytotoxicity to normal cells. DPP-23 represents a promising novel therapeutic agent for the selective production of ROS in cancer cells.
    Clinical cancer research : an official journal of the American Association for Cancer Research. 06/2014;
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    Dongsoo Koh, Yoongho Lim, Alan J Lough
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    ABSTRACT: The asymmetric unit of the title compound, C20H18N2O2, contains two independent mol-ecules in which the dihedral angles between the naphthalene ring system [r.m.s. deviations = 0.012 (1) and 0.015 (1) Å] and the benzene ring are 71.65 (6) and 74.51 (6)°. In the crystal, pairs of N-H⋯O hydrogen bonds form two independent inversion dimers with graph-set notation R 2 (2)(14). In addition, each mol-ecule contains an intra-molecular O-H⋯N hydrogen bond with an S(6) motif.
    Acta Crystallographica Section E Structure Reports Online 04/2014; 70(Pt 4):o464. · 0.35 Impact Factor
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    ABSTRACT: Ovarian carcinoma remains the most lethal among gynecological cancers. Chemoresistance is a clinical problem that severely limits treatment success. To identify potent anticancer agents against the cisplatin-resistant human ovarian cancer cell line A2780/Cis, 26 polyphenols bearing a cinnamaldehyde scaffold were synthesized. Structural differences in their inhibitory effect on clonogenicity of A2780/Cis cells were elucidated using comparative molecular field analysis and comparative molecular similarity indices analysis. Structural conditions required for increased inhibitory activity can be derived based on the analysis of their contour maps. The two most active compounds (16 and 19) were selected and further characterized their biological activities. We found that compounds 16 and 19 trigger cell cycle arrest at the G2/M phase and apoptotic cell death in cisplatin-resistant A2780/Cis human ovarian cancer cells. The molecular mechanism of compound 16 was elucidated using in vitro aurora A kinase assay, and the binding mode between the compound 16 and aurora A kinase was interpreted using in silico docking experiments. The findings obtained here may help us develop novel plant-derived polyphenols used for potent chemotherapeutic agents. In conclusion, compounds 16 and 19 could be used as promising lead compounds for the development of novel anticancer therapies in the treatment of cisplatin-resistant ovarian cancers.
    Bioorganic & medicinal chemistry 02/2014; · 2.82 Impact Factor
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    ABSTRACT: In recent years, a number of adulterants in foods, such as melamine in infant formula and horse meat in beef, have been reported. For ensuring the food safety, proper regulation of these adulterated foods is necessary. In this work, we have studied an adulteration of maltitol in a commercial galactooligosaccharide (GOS) product using the flow-injection electrospray ionization tandem mass spectrometry (ESI-MS/MS) and the MassBank database. Firstly, qualitative analysis of the adulterated maltitol in a GOS product was achieved by the flow-injection ESI-MS/MS in negative ion mode. Secondly, mass spectral data obtained from the ESI-MS/MS were compared with the MassBank database. Lastly, final confirmation and quantitative analysis of the adulterated maltitol was carried out by HPLC-RI using a reference material. As a result, content of the adulterated maltitol in a GOS product was determined to be 60.2%, which was not indicated on the label. On the other hand, unlike the labeled statement, content of raffinose was only 18.4% instead of labeled 100%. Although maltitol is generally considered to be safe, it is also known that large quantities of maltitol can have a laxative effect. Furthermore, consumers have the rights to know what are in the foods they eat. Therefore, food adulterations, including this case of maltitol, should be properly controlled by the regulatory authorities.
    Food Control 02/2014; 36(1):280-286. · 2.74 Impact Factor
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    ABSTRACT: Wound healing plays an important role in protecting the human body from external infection. Cell migration and proliferation of keratinocytes and dermal fibroblasts are essential for proper wound healing. Recently, several studies have demonstrated that secondary compounds produced in plants could affect skin cells migration and proliferation. In this study, we identified a novel compound DK223 ([1E,2E-1,2-bis(6-methoxy-2H-chromen-3-yl)methylene]hydrazine) that concomitantly induced human keratinocyte migration and dermal fibroblast proliferation. We evaluated the regulation of epithelial and mesenchymal protein markers, such as E-cadherin and Vimentin, in human keratinocytes, as well as extracellular matrix (ECM) secretion and metalloproteinase families in dermal fibroblasts. DK223 upregulated keratinocyte migration and significantly increased the epithelial marker E-cadherin in a time-dependent manner. We also found that reactive oxygen species (ROS) increased significantly in keratinocytes after 2 h of DK223 exposure, returning to normal levels after 24 h, which indicated that DK223 had an early shock effect on ROS production. DK223 also stimulated fibroblast proliferation, and induced significant secretion of ECM proteins, such as collagen I, III, and fibronectin. In dermal fibroblasts, DK223 treatment induced TGF-β1, which is involved in a signaling pathway that mediates proliferation. In conclusion, DK223 simultaneously induced both keratinocyte migration via ROS production and fibroblast proliferation via TGF-β1 induction.
    International Journal of Molecular Sciences 01/2014; 15(7):13091-110. · 2.46 Impact Factor
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    ABSTRACT: The natural chalcones and their derivatives exhibit many biological activities, such as anti-inflammatory and antitumoral. However, the precise mechanism(s) of action of benzochalcone derivatives is currently unknown. Here, a set of benzochalcones was synthesized, and the molecular mechanisms underlying inhibition of tumor growth were investigated. Colony forming assays revealed that among tested compounds, 2-hydroxy-4-methoxy-2',3'-benzochalcone (HymnPro) most effectively inhibited the clonogenicity of Capan-1 human pancreatic cancer cells. HymnPro inhibited cell proliferation in several human solid tumor cell lines and suppressed xenografted tumor growth in nude mice. Mechanistically, HymnPro induced cell cycle arrest at the G2/M phase, followed by an increase in apoptotic cell death. These events were associated with the inhibition of tubulin polymerization through binding of HymnPro to tubulin, leading to the formation of abnormal mono- or multipolar mitotic microtubule structures accompanied by spherical arrangement of multinucleated chromosomes. Furthermore, HymnPro activated caspase-2, -9, -3, and -7 and increased the cleavage of poly(ADP-ribose) polymerase (PARP). HymnPro increased the phosphorylation of JNK1/2, Erk1/2, and p38 kinase. Pretreatment with SP600125, U0126, or SB600125 abrogated HymnPro-induced activation of caspase-3, and -7 and the cleavage of PARP, suggesting that MAPK signalings are involved in HymnPro-induced apoptosis. We conclude that a novel HymnPro compound exerts antitumor activity by disrupting microtubule assembly, which leads to mitotic arrest and sequential activation of caspase pathway, resulting in apoptosis.
    Journal of Agricultural and Food Chemistry 12/2013; · 2.91 Impact Factor
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    ABSTRACT: Cell migration plays an important role in multicellular development and preservation. Because wound healing requires cell migration, compounds promoting cell migration can be used for wound repair therapy. Several plant-derived polyphenols are known to promote cell migration, which improves wound healing. Previous studies of flavonoids on cell lines have focused on their inhibitory effects and not on wound healing. In addition, studies of flavonoids on wound healing have been performed using mixtures. In this study, individual flavonoids were used for cellular migration measurements. Relationships between the cell migration effects of flavonoids and their structural properties have never been reported. Here, we investigated the migration of keratinocytes caused by 100 flavonoids and examined their relationships using hologram quantitative structure-activity relationships. The structural conditions responsible for efficient cell migration on keratinocyte cell lines determined from the current study will facilitate the design of flavonoids with improved activity.
    Phytomedicine: international journal of phytotherapy and phytopharmacology 11/2013; · 2.97 Impact Factor
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    ABSTRACT: Structure-activity relationship (SAR) calculations were used to find monoamine oxidase-B (MAO-B) inhibitors by identifying pharmacophores exhibiting high inhibitory activities. Several such chromenylchalcones were designed and synthesized accordingly. Their inhibitory effects on MAO-B were determined using an HPLC-based method and an MAO-B enzyme assay kit. (E)-3-(6-Methoxy-2H-chromen-3-yl)-1-(2-methoxyphenyl)prop-2-en-1-one exhibited a half-maximal inhibitory concentration of 320nM. Its molecular-level binding mode with the three-dimensional structure of MAO-B was elucidated using an in silico docking study. The chromenylchalcone scaffold, which is derived from natural products including isoflavonoids and chalcones, had not been previously reported as an MAO-B inhibitor.
    Bioorganic & medicinal chemistry 10/2013; · 2.82 Impact Factor
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    ABSTRACT: Colorectal cancer is the third and fourth leading cause of cancer in males and females, respectively. Flavonoids, including chalcones, are secondary metabolites in plants that exhibit diverse biological activities, including antibacterial, antimalarial, and antitumor activities. In order to find potent and novel chemotherapy drugs for colorectal cancer, a series of benzochalcone derivatives, in which an α,β-unsaturated carbonyl group was replaced with a pyrazoline, was designed and synthesized. A clonogenic survival assay was performed with each derivative to evaluate antitumor activity. 1-(5-(2,4-Dimethoxyphenyl)-4,5-dihydro-1H-pyrazol-3-yl)naphthalen-2-ol (derivative 7) had the most potent inhibitory effect on the long-term clonogenicity of HCT116 human colorectal cancer cells (IC50=2.4μM). The results of Western blot and flow cytometric analyses suggested that derivative 7 could inhibit the proliferation of colorectal cancer cells through inhibition of cell cycle progression and induction of apoptosis. To elucidate its molecular mechanism, in vitro kinase binding assays were carried out, which demonstrated that derivative 7 inhibited aurora kinases A and B selectively. The binding modes between the compound and aurora kinases were interpreted using in silico docking experiments to explain the selective inhibitory effects on aurora kinases A and B. These findings will facilitate the design of potent novel benzochalcones as anticancer agents.
    Bioorganic & medicinal chemistry 09/2013; · 2.82 Impact Factor
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    ABSTRACT: Growth-regulated oncogene α (GROα) plays an important role in a wide range of normal and pathological conditions, including inflammation, angiogenesis, wound healing, tumor invasion, and metastasis. Egr-1 is a member of the zinc-finger transcription factor family induced by diverse stimuli, including TNFα. However, the role of Egr-1 in GROα expression was previously unknown. This study shows that Egr-1 directly binds to the GROα promoter and transactivates the GROα gene. Silencing of Egr-1 by expression of Egr-1 siRNA abrogated TNFα-induced GROα transcription. We also found that Egr-1 mediates ERK and JNK MAPKs-dependent GROα transcription upon TNFα stimulation. Our findings suggest that Egr-1 may play an important role in tumor development through transactivation of the GROα gene in response to TNFα within the tumor microenvironment.
    Biochimica et Biophysica Acta 07/2013; · 4.66 Impact Factor
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    ABSTRACT: To find potent new chemotherapy drugs, we designed and synthesized a series of naphthochalcones bearing naphthalenyl-phenyl-pyrazoline moieties. The complete (1) H and (13) C NMR data for these compounds are reported here and can be used to identify further new naphthochalcones bearing the desired pyrazoline moieties. Copyright © 2013 John Wiley & Sons, Ltd.
    Magnetic Resonance in Chemistry 07/2013; · 1.53 Impact Factor
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    ABSTRACT: Chalcones are known to act on various physiological targets. As a result, structural modifications of chalcones have been studied extensively. Benzochalcones, in which the A-ring of chalcone is substituted with a naphthalene unit, inhibits breast cancer resistance protein. Chalcones in which the α,β-unsaturated carbonyl group is switched with a pyrazoline moiety are potent cytotoxic agents against various cancer cell lines, and chalcones with a pyrazoline-1-carbothioamide group instead of an α,β-unsaturated carbonyl group exhibit antimicrobial activities. The present report describes hybrid molecules designed from benzochalcone and pyrazoline-carbothioamide. Methoxylation of plant-derived polyphenols alters their hydrophobicity, resulting in changes in biological function and intracellular compartmentation. In the current study, 22 novel methoxylated 3-(naphthalen-2-yl)-N,5-diphenyl-pyrazoline-1-carbothioamide derivatives were prepared. This report provides complete assignments of their (1) H and (13) C NMR data, which can be used to subsequently identify chalcones bearing pyrazoline-carbothioamide groups. Copyright © 2013 John Wiley & Sons, Ltd.
    Magnetic Resonance in Chemistry 06/2013; · 1.53 Impact Factor
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    ABSTRACT: 2-chloro-10-[3(-dimethylamino)propyl]phenothiazine mono hydrochloride (chlorpromazine; CPZ) is an antipsychotic agent, that was originally developed to control psychotic disorders. The cytotoxic properties of the CPZ are well known, but its mechanism of action is poorly understood. Here, we investigated the role of apoptosis and autophagy in CPZ-induced cytotoxicity in U-87MG glioma cells. CPZ treatment inhibited cell proliferation and long-term clonogenic survival. Additionally, CPZ triggered autophagy, as indicated by electron microscopy and accumulation of the membrane form of LC3 (LC3-II); however, CPZ did not induce apoptosis. Inhibition of autophagy by expression of Beclin 1 siRNA in U-87MG cells attenuated CPZ-induced LC3-II formation. Furthermore, U-87MG cells expressing Beclin1 siRNA attenuated CPZ-induced cell death. CPZ inhibited phosphatidylinositol 3-kinase (PI3K)/AKT/ mTOR pathway in U-87MG cells. Treatment with LY294002, a PI3K inhibitor, alone increased the accumulation of LC3-II and potentiated the effect of CPZ. By contrast, exogenous expression of AKT partially inhibited CPZ-induced LC3-II formation. When U-87MG cells were implanted into the brain of athymic nude mouse, CPZ triggered autophagy and inhibited xenograft tumor growth. These results provided the first evidence that CPZ-induced cytotoxicity is mediated through autophagic cell death in PTEN-null U-87MG glioma cells by inhibiting PI3K/AKT/mTOR pathway.
    Carcinogenesis 05/2013; · 5.64 Impact Factor
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    ABSTRACT: Due to toxicity problems, various plant-derived compounds have been screened to find the chemotherapeutic agents. As anticancer therapeutic agents, chalcones have advantages such as poor interaction with DNA and low risk of mutagenesity. Chromenones show anticancer activities too. Therefore, hybrids of chalcone and chromenone may be potent chemotherapeutic agents. We prepared 16 synthetic chromenylchalcones and applied a clonogenic long-term survival assay method for them on HCT116 human colorectal cancer cell lines. One of chromenylchalcones tested here, chromenylchalcone 11, showed IC50 of 93.1nM which can be competed with the IC50 values of well-known flavonoids such as catechin gallate and epicatechin gallate. Further biological experiments including cell cycle analysis, apoptosis assay, Western blot analysis, and immunofluorescent microscopy were carried out for this compound. In addition, in vitro kinases binding assay performed to explain its molecular mechanism demonstrated the compound inhibited aurora kinases. The binding modes between chromenylchalcone 11 and aurora kinases were elucidated using in silico docking experiments. These findings could be used for designing cancer therapeutic or preventive plant-derived chromenylchalcone agents.
    Bioorganic & medicinal chemistry 05/2013; · 2.82 Impact Factor
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    ABSTRACT: In the title mol-ecule, C18H18O4, the C=C bond of the central enone group adopts a trans conformation. The relative conformation of the C=O and C=C bonds is s-cisoid. The dihedral angle between the planes of the benzene rings is 29.49 (12)°. In the crystal, weak C-H⋯O hydrogen bonds link the mol-ecules into chains along [010].
    Acta Crystallographica Section E Structure Reports Online 05/2013; 69(Pt 5):o666. · 0.35 Impact Factor
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    ABSTRACT: Chalcones are of interest to medicinal chemists because their structures can be easily modified with various functional groups. The syntheses and biological activities of chalcones from natural sources are well known. In this study, 24 2'-hydroxychalcones bearing methoxy substituents were synthesized, among which five are new. The NMR data for all synthesized chalcones are described for the first time. The complete assignments of the (1) H and (13) C NMR data can be used for the identification of newly discovered and widely isolated, synthesized chalcones. Copyright © 2013 John Wiley & Sons, Ltd.
    Magnetic Resonance in Chemistry 04/2013; · 1.53 Impact Factor
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    Yoongho Lim, Dongsoo Koh
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    ABSTRACT: In the title mol-ecule, C18H18O4, the dihedral angle between the benzene rings is 52.52 (7)°. The C=C bond of the central enone group adopts a trans conformation. The relative conformation of the two double bonds in the enone group is s-transoid. In the crystal, mol-ecules are linked by pairs of weak C-H⋯O hydrogen bonds, forming inversion dimers.
    Acta Crystallographica Section E Structure Reports Online 04/2013; 69(Pt 4):o514. · 0.35 Impact Factor
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    ABSTRACT: Flavonoids are major active ingredients in plants and are considered components of food that provide medical or health benefits. They have diversified structures and have effects on human health, including wound healing induction. More than a hundred flavonoids were screened for HaCaT keratinocytes cellular migration measurements and the relationships between their structural properties and the effects promoting cellular migration were examined. Here, among flavonoids used in the previous structure-activity relationship calculations, 4′,6,7-trimethoxyisoflavone (TMF) was one of the compounds showing the best activity, so that its molecular mechanism of the wound healing effect on HaCaT keratinocytes was investigated in more detail. Our data revealed that TMF increased the wound healing rate, but not the proliferation rate, in a dose-dependent manner. Treatment of keratinocytes with TMF influenced signaling pathways, affecting the phosphorylation of AKT and ERK in a time-dependent manner. TMF also induced the cell–cell adhesion protein E-cadherin, which is essential for promoting collective cell migration. Furthermore, the TMF treatment group also showed higher ROS and NOX2 transcriptional and protein levels. Correlating with matrix metalloproteinase induction by TMF, levels of extracellular matrix proteins such as collagens I and III were significantly lower in the treatment group. To confirm that the effects of TMF occur through the NOX2 pathway, we co-treated cells with TMF plus an NADPH inhibitor (DPI) or a ROS scavenger (NAC). Western blotting revealed that DPI and NAC attenuated the effect of TMF, suggesting that TMF induces ROS through the NOX2 pathway and regulates keratinocyte migration. In summary, TMF promotes wound healing through NOX2 induction, which leads to collective migration and MMP activation.
    Phytomedicine: international journal of phytotherapy and phytopharmacology 01/2013; · 2.97 Impact Factor
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    ABSTRACT: Plant-derived polyphenols are being tested as chemopreventive agents; some polyphenols arrest the cell cycle at G1 phase, whereas others inhibit cell cycle proliferation at G2/M phase. Therefore, polyphenols have been proposed to inhibit cell cycle progression at different phases via distinct mechanisms. Indeed, our previous studies showed that small structural differences in polyphenols cause large differences in their biological activities; however, the details of the structural properties causing G1 cell cycle arrest remain unknown. In this study, we prepared 27 polyphenols, including eight different scaffolds, to gain insight into the structural conditions that arrest the cell cycle at G1 phase in a quantitative structure-activity relationship study. We used cell cycle profiles to determine the biophores responsible for G1 cell cycle arrest and believe that the biophores identified in this study will help design polyphenols that cause G1 cell cycle arrest.
    International Journal of Molecular Sciences 01/2013; 14(8):16970-85. · 2.46 Impact Factor
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Publication Stats

950 Citations
383.11 Total Impact Points


  • 2001–2014
    • Konkuk University
      • • Department of Bioscience and Technology
      • • Bio/Molecular Informatics Center
      Sŏul, Seoul, South Korea
  • 2013
    • Dongduk Women's University
      Sŏul, Seoul, South Korea
  • 2009–2013
    • Jeju National University
      Tse-tsiu, Jeju, South Korea
  • 2012
    • Korea Basic Science Institute KBSI
      • Jeonju Center
      Seoul, Seoul, South Korea
  • 2009–2011
    • Konkuk University Medical Center
      Changnyeong, South Gyeongsang, South Korea
  • 2006–2011
    • Hanyang University
      • • Department of Molecular and Life Science
      • • Major in Medical Genetics
      Seoul, Seoul, South Korea
  • 2005–2009
    • Gwangju Institute of Science and Technology
      • • International Environmental Research Center
      • • School of Environmental Science and Engineering
      Kwangju, Gwangju, South Korea
    • Hanyang University Medical Center
      Sŏul, Seoul, South Korea
  • 2002–2004
    • Kunsan National University
      Gunzan, North Jeolla, South Korea
    • Sungkyunkwan University
      • Department of Chemistry
      Seoul, Seoul, South Korea
  • 2003
    • Seoul National University
      • Department of Agricultural Biotechnology
      Seoul, Seoul, South Korea