Jung-Hyun Shim

Mokpo National University, Mokuho, Jeollanam-do, South Korea

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Publications (62)200.05 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to investigate anti-inflammatory and anti-cancer effects of honokiol (HK) in two oral squamous cancer cell carcinoma (OSCC) cell lines, HN22 and HSC4, through the regulation of inducible nitric oxide synthase (iNOS) and endoplasmic reticulum resident protein 44 (ERp44). Griess assay, zymography, and quantitative PCR were performed to study iNOS expression and subsequent nitric oxide (NO) production in OSCC cell lines. Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomic analysis was used to elucidate the proteins associated with ER stress and cellular cytotoxic response induced by HK. Pull-down assay and molecular modeling were performed to better understand how HK interacts with ERp44. In vitro and in vivo experiments in which ERp44 expression was knocked down were performed to better understand the effects of ERp44 on a cellular level and anti-cancer effects of HK. Expression levels of iNOS and subsequent NO secretion were reduced in OSCC cell lines treated with HK. ERp44 was significantly decreased in OSCC cell lines by HK treatment. HK directly bound to ERp44, and ERp44 knock-down significantly inhibited oral cancer cell proliferation and colony formation. Moreover, HK treatment effectively inhibited tumor growth and ERp44 levels in BALB/c nude mice bearing HN22 cell xenografts. Our findings suggest that HK inhibited inflammation and induced apoptosis by suppressing both iNOS/NO and ERp44 expression in HN22 and HSC4 cells and xenograft tumors, and thus could be a potent anti-inflammatory and anti-cancer drug candidate for human oral cancer treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Biomaterials 06/2015; 53. DOI:10.1016/j.biomaterials.2015.02.091 · 8.31 Impact Factor
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    ABSTRACT: Recently, biphenolic components derived from the Magnolia family have been studied for anti-cancer, anti-stress, and anti-inflammatory pharmacological effects. However, the pharmacological mechanism of action of 4-O-methylhonokiol (MH) is not clear in oral cancer. The aim of this study was to investigate the role of MH in apoptosis and its molecular mechanism in oral squamous cell carcinoma (OSCC) cell lines, HN22 and HSC4, as well as tumor xenografts. Here, we demonstrated that MH decreased cell growth and induced apoptosis in HN22 and HSC4 cells through the regulation of specificity protein 1 (Sp1). We employed several experimental techniques such as MTS assay, DAPI staining, PI staining, Annexin-V/7-ADD staining, RT-PCR, western blot analysis, immunocytochemistry, immunohistochemistry, TUNEL assay and in vivo xenograft model analysis. MH inhibited Sp1 protein expression and reduced Sp1 protein levels via both proteasome-dependent protein degradation and inhibition of protein synthesis in HN22 and HSC4 cells; MH did not alter Sp1 mRNA levels. We found that MH directly binds Sp1 by Sepharose 4B pull-down assay and molecular modeling. In addition treatment with MH or knocking down Sp1 expression, suppressed oral cancer cell colony formation. Moreover, MH treatment effectively inhibited tumor growth and Sp1 levels in BALB/c nude mice bearing HN22 cell xenografts. These results indicated that MH inhibited cell growth, colony formation and also induced apoptosis via Sp1 suppression in OSCC cells and xenograft tumors. Thus MH is a potent anti-cancer drug candidate for oral cancer. Copyright © 2015. Published by Elsevier Ltd.
    The international journal of biochemistry & cell biology 05/2015; 64. DOI:10.1016/j.biocel.2015.05.007 · 4.24 Impact Factor
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    ABSTRACT: β-lapachone (β-lap) is a naturally occurring quinone obtained from the bark of lapacho tree (Tabebuia avellanedae) with anti-proliferative properties against various cancers. The present study investigated the cell proliferation and apoptosis effect of β-lap on two oral squamous cell carcinoma lines (OSCCs). We carried out a series of 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl-2H-tetrazolium (MTS) assays, 4',6-diamidino-2-phenylindole (DAPI) staining, cell cycle analysis, and western blot analysis to characterize β-lap and its underlying signaling pathway. We demonstrated that β-lap-treated cells significantly reduced cell proliferation but increased DNA condensation and increased sub-G1 population in OSCCs. Particularly, β-lap suppresses activation of transcription factor specificity protein 1 (Sp1) followed by apoptosis in a concentration-dependent manner in OSCCs. Furthermore, β-lap modulated protein expression levels of cell cycle regulatory proteins and apoptosis-related proteins that are known as Sp1 target genes, resulting in apoptosis. Our results collectively indicated that β-lap was able to modulate Sp1 transactivation and induce apoptosis through the regulation of cell cycle and apoptosis-related proteins. Therefore, β-lap may be used in cancer prevention and therapies to improve clinical outcome as an anticancer drug candidate.
    International Journal of Oncology 04/2015; DOI:10.3892/ijo.2015.2972 · 2.77 Impact Factor
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    ABSTRACT: 17-(Dimethylaminoethylamino)-17-demethoxygeldanamycin (DMAG) acts as an inhibitor of heat shock protein 90 (HSP 90), which serves as a nodal protein of diverse signaling networks leading to a variety of biological implications. HSP90 plays the role of a chaperone for a variety of client proteins including receptor interacting protein 1 (RIP1). Since RIP1 and RIP3 are, respectively, required for zVAD- and tumor necrosis factor alpha (TNFα)-mediated necrotic cell death, we pursued to address the effects of DMAG on receptor- and nonreceptor-mediated necroptotic cell death. DMAG facilitated the degradation of receptor interacting protein 3 (RIP3) as well as RIP1, a known client protein of HSP90, in L929 cells. Consequently, DMAG rendered cells more sensitive to TNFα stimulation while it rescued cells from necrotic cell death caused by zVAD. From this study, we propose that DMAG-downregulated RIP1 can shift cell death typing from necroptosis to apoptosis. In contrast, the protective effect of DMAG on zVAD-induced cytotoxicity could be partly explained by the fact that zVAD mediates cytotoxicity via a RIP1-dependent route. In summary, functional disruption of HSP90 by DMAG destabilized necroptosis proteins RIP1 and RIP3, which in turn regulated zVAD- and TNFα-induced necroptosis. Therefore, pharmacological modulation of necroptotic cell death through HSP90 could be a promising strategy for overcoming cancer drug resistance or protecting ischemic cell death.
    Pharmazie 03/2015; 70(3). DOI:10.1691/ph.2015.4689 · 1.00 Impact Factor
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    ABSTRACT: Licochalcone A (LCA) is a natural product derived from the roots of Glycyrrhiza inflata exhibiting a wide range of bioactivities such as antitumor, anti-oxidant and anti-bacterial effects. Malignant pleural mesothelioma (MPM) is an extremely aggressive type of cancer with a poor prognosis because of its rapid progression. However, LCA has not been investigated concerning its effects on MPM. Preliminarily, we observed that LCA negatively modulated not only cell growth, but also specificity protein 1 (Sp1) expression in MSTO-211H and H28 cell lines. It was found that IC50 values of LCA for growth inhibition of MSTO-211H and H28 cells were approximately 26 and 30 µM, respectively. Consistent with downregulation of Sp1, expression of Sp1 regulatory proteins such as Cyclin D1, Mcl-1 and Survivin was substantially diminished. Mechanistically, LCA triggered the mitochondrial apoptotic pathway by affecting the ratio of mitochondrial proapoptotic Bax to anti-apoptotic Bcl-xL. Bid induced loss of mitochondrial membrane potential, eventually leading to multi-caspase activation and increased sub-G1 population. Moreover, nuclear staining with DAPI highlighted nuclear condensation and fragmentation of apoptotic features. Flow cytometry analyses after staining cells with Annexin V and propiodium iodide corroborated LCA-mediated apoptotic cell death of MPM cells. In conclusion, these results present that LCA may be a potential bioactive material to control human MPM cells by apoptosis via the downregulation of Sp1.
    International Journal of Oncology 01/2015; 46(3). DOI:10.3892/ijo.2015.2839 · 2.77 Impact Factor
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    ABSTRACT: The most active anticancer component in green tea is epigallocatechin-3-gallate (EGCG). Protein interaction with EGCG is a critical step for mediating the effects of EGCG on the regulation of various key molecules involved in signal transduction. By using computational docking screening methods for protein identification, we identified a serine/threonine kinase, 90-kDa ribosomal S6 kinase (RSK2), as a novel molecular target of EGCG. RSK2 includes two kinase catalytic domains in the N-terminal (NTD) and the C-terminal (CTD) and RSK2 full activation requires phosphorylation of both terminals. The computer prediction was confirmed by an in vitro kinase assay in which EGCG inhibited RSK2 activity in a dose-dependent manner. Pull-down assay results showed that EGCG could bind with RSK2 at both kinase catalytic domains in vitro and ex vivo. Furthermore, results of an ATP competition assay and a computer-docking model showed that EGCG binds with RSK2 in an ATP-dependent manner. In RSK2+/+ and RSK2-/- murine embryonic fibroblasts, EGCG decreased viability only in the presence of RSK2. EGCG also suppressed epidermal growth factor-induced neoplastic cell transformation by inhibiting phosphorylation of histone H3 at Ser10. Overall, these results indicate that RSK2 is a novel molecular target of EGCG.
    PLoS ONE 01/2015; 10(6):e0130049. DOI:10.1371/journal.pone.0130049 · 3.53 Impact Factor
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    ABSTRACT: 7,8-Dihydroxyflavone (7,8-DHF) is a member of the flavonoid family and has recently been identified as a brain-derived neurotrophic factor mimetic that selectively activates tropomyosin-receptor kinase B with high affinity. The antioxidant and anticancer effects of 7,8-DHF have been reported. However, the pharmacological mechanisms of 7,8-DHF in oral cancer are unclear. Thus, we investigated the mechanisms of the antiproliferative action of 7,8-DHF on HN22 and HSC4 oral squamous cell carcinoma cell lines. We demonstrated that 7,8-DHF decreased cell growth and induced apoptosis in the HN22 and HSC4 cells through regulation of specificity protein 1 (Sp1) using the MTS assay, DAPI staining, Annexin V, propidium iodide staining, reverse transcription-polymerase chain reaction, immunocytochemistry, pull-down assay and western blot analysis. The results showed that the Sp1 protein bound with 7,8-DHF in the HN22 and HSC4 cells. Taken together, the results suggest that 7,8-DHF could modulate Sp1 transactivation and induce apoptotic cell death by regulating the cell cycle and suppressing antiapoptotic proteins. Furthermore, 7,8-DHF may be valuable for cancer prevention and better clinical outcomes.
    Oncology Reports 11/2014; 33(2). DOI:10.3892/or.2014.3632 · 2.19 Impact Factor
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    ABSTRACT: Esculetin (6,7-dihydroxycoumarin), a coumarin compound, is known to inhibit proliferation and induce apoptosis in several types of human cancer cells and is regarded as a promising chemotherapeutic agent. The purpose of the present study was to investigate the anti-proliferative effects of esculetin on two oral squamous cell carcinoma (OSCC) cell lines, HN22 and HSC4, through regulation of specificity protein 1 (Sp1). We examined the apoptotic effects of esculetin were measured by MTS assay, DAPI staining, Annexin V, PI staining, RT-PCR, western blot analysis and immunocytochemistry in HN22 and HSC4 cells. Taken together, the results of the present study indicate that esculetin had anti-proliferative effect on the growth of OSCC cells (HN22 and HSC4) in a dose- and time-dependent manner. The treatment of HN22 and HSC4 cells with esculetin led to a significant reduction in growth and induced apoptosis, followed by the regulation of Sp1 and Sp1 regulatory protein. This indicates that esculetin inhibited cell growth and induced apoptosis by suppressing Sp1 in HN22 and HSC4 cells, suggesting it to be a potent anticancer drug candidate for oral cancer.
    International Journal of Oncology 10/2014; 46(1). DOI:10.3892/ijo.2014.2700 · 2.77 Impact Factor
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    ABSTRACT: Cordycepin is an adenosine analog originally extracted from Cordyceps militaris that possesses many pharmacological effects including immune activation and antioxidant and antitumor effects. However, the underlying relationship between apoptosis and telomerase activity in response to cordycepin exposure has not been investigated. In this study, we found that cordycepin-induced apoptosis of human leukemia cells (H937 and THP-1 cells) was associated with inactivation of telomerase and downregulation of human telomerase reverse transcriptase (hTERT) as well as the transcription factors c-Myc and Sp1, which are required for basal transcription from the hTERT gene promoter. Cordycepin also attenuated the activation of phosphoinositide-3-kinase (PI3K)/Akt signaling, thereby reducing phosphorylation and nuclear translocation of hTERT. We further showed that the PI3K inhibitor LY29004 significantly decreased telomerase activity in cordycepin-treated cells and increased cordycepin-induced cell death. These findings demonstrate that cordycepin is cytotoxic to human leukemia cells and suppresses telomerase activity through transcriptional and post-translational suppression of hTERT by inactivating the PI3K/Akt signaling pathway.
    Journal of Bioscience and Bioengineering 10/2014; 119(3). DOI:10.1016/j.jbiosc.2014.08.008 · 1.79 Impact Factor
  • 09/2014; 22(3):469-481. DOI:10.11625/KJOA.2014.22.3.469
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    ABSTRACT: Organ transplantation is the most effective medical therapy for End-stage renal disease patients; however, there is a critical shortage of human donor organs. Therefore, xenotransplantation using genetically modified cloned porcine kidney is considered as a viable solution, but its fundamental therapeutic mechanism and difference from non-cloned porcine or human kidney for its clinical application is not well known. Here, we performed proteomic analysis to investigate the differentially expressed molecules in kidney tissue obtained from cloned porcine by SCNT, when compared with normal porcine kidney in same age as a control. A total of 80 protein spots were differentially expressed between cloned porcine kidney and control kidney, including apoptotic proteins, structural and anti-oxidant related proteins. Furthermore, very interestingly, the differential expression pattern of PrxII in the cloned porcine kidney was distinguishable from that in the control kidney in terms of the pI and molecular weight. Along with this, apoptotic marker proteins were up-regulated in the cloned porcine kidney. We confirmed that these alterations were induced by post-translational modification such as phosphorylation, which mediated by JNK. With this result, we also observed that the down-regulation of JNK activity was caused by blockage of phosphorylation in PrxII T89A region. Taken together, cloned porcine kidney is more susceptible in JNK-induced apoptosis caused by PrxII phosphorylation, in oxidative stress condition. These results will be helpful in the application of cloned porcine xeno-transplants for treating End-stage renal disease patients in a clinical setting.
    The International Journal of Biochemistry & Cell Biology 06/2014; 53. DOI:10.1016/j.biocel.2014.05.039 · 4.24 Impact Factor
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    ABSTRACT: Licochalcone A (LCA), a chalconoid derived from root of Glycyrrhiza inflata, has been known to possess a wide range of biological functions such as antitumor, anti-angiogenesis, antiparasitic, anti-oxidant, antibacterial and anti-inflammatory effects. However, the anticancer effects of LCA on oral squamous cell carcinoma (OSCC) have not been reported. Our data showed that LCA inhibited OSCC cell (HN22 and HSC4) growth in a concentration- and time-dependent manner. Mechanistically, it was mediated via downregulation of specificity protein 1 (Sp1) expression and subsequent regulation of Sp1 downstream proteins such as p27, p21, cyclin D1, Mcl-1 and survivin. Here, we found that LCA caused apoptotic cell death in HSC4 and HN22 cells, as characterized by sub-G1 population, nuclear condensation, Annexin V staining, and multi-caspase activity and apoptotic regulatory proteins such as Bax, Bid, Bcl?xl, caspase-3 and PARP. Consequently, this study strongly suggests that LCA induces apoptotic cell death of OSCC cells via downregulation of Sp1 expression, prompting its potential use for the treatment of human OSCC.
    International Journal of Oncology 05/2014; 45(2). DOI:10.3892/ijo.2014.2461 · 2.77 Impact Factor
  • Ji Hyun Bae, Jung-Hyun Shim, Young Sik Cho
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    ABSTRACT: Necroptosis is an active and well-orchestrated necrosis, distinctive from apoptosis in microscopic structure, and biochemical and molecular features. Unlike apoptosis-undergoing cells, which are removed by macrophage or neighboring cells, necrotic cell death releases danger signals and provokes inflammation, and further a severe damage to neighbor tissue. A regulated necrosis, termed as necroptosis or programmed necrosis, is emerging as a new paradigm of cell death that can be activated when apoptotic machinery is genetically or pathogenically defective. It plays biological significances in pathogenesis of a variety of inflammatory diseases as well as in a beneficial innate immune defense mechanism. This review highlights the identification of hits against necroptosis, and comprehensive approaches to discovery of small molecules that regulate necroptotic cell death. Also, the signaling molecular mechanism of necroptosis and future clinical uses of necroptosis inhibitor will be described in brief.
    Archives of Pharmacal Research 04/2014; 37(6). DOI:10.1007/s12272-014-0385-6 · 1.75 Impact Factor
  • 03/2014; 22(1):167-182. DOI:10.11625/KJOA.2014.22.1.167
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    ABSTRACT: Maillard reaction products are known to have anti inflammatory property. Objective of this study was to assess anti-arthritis effects of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal and its action mechanisms. Lipopolysaccharide (LPS)-activated macrophage (RAW264.7) and synoviocytes were treated with (E)-2,4-bis(p-hydroxyphenyl)-2-butenal for in vitro assay. (E)-2,4-bis(p-hydroxyphenyl)-2-butenal (5 mg/kg) was also periorally administered for 30 days to collagen (50 μg/g) induced arthritic mice. Clinical score, histopathological exam, NO generation, iNOS and COX2 expression, and NF-κB/IKK and STAT3 activities were determined in cultured cell and joint tissues of mice. Binding of (E)-2,4-bis(p-hydroxyphenyl)-2-butenal to STAT3 was evaluated by a Pull-down assay and its binding site was predicted using molecular docking study with Autodock VINA. (E)-2,4-bis(p-hydroxyphenyl)-2-butenal (2.5-10 μg/ml) inhibited LPS (1 μg/ml)-induced NO generation, iNOS and COX2 expression, and NF-κB/IKK and STAT3 activities in macrophage and synoviocytes. (E)-2,4-bis(p-hydroxyphenyl)-2-butenal suppressed the collagen induced arthritic responses through inhibition of the expression of iNOS and COX2, and NF-κB/IKK and STAT3 activities, and also reduced the extent of bone destruction and fibrosis in joint tissues. A Pull-down assay proved that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal interfere with the binding of ATP to STAT3. Subsequent docking study proposes that (E)-2,4-bis(p-hydroxyphenyl)-2-butenal binds to the the DNA binding interface of STAT3 possibly causing ATP binding to STAT3 in an allosteric manner. (E)-2,4-bis(p-hydroxyphenyl)-2-butenal exerted its anti-inflammatory and anti-arthritic effects through inhibition of NF-κB/STAT3 pathway via direct binding to STAT3, and that it could be a useful agent for the treatment of arthritic disease.
    British Journal of Pharmacology 02/2014; DOI:10.1111/bph.12619 · 4.99 Impact Factor
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    ABSTRACT: The Maillard reaction is a chemical reaction occurring between a reducing sugar and an amino acid, generally requiring thermal processing. Maillard reaction products (MRPs) have antioxidant, antimutagenic, and antibacterial effects; though 2,4-bis (p-hydroxyphenyl)-2-butenal (HPB242), a fructose-tyrosine MRP, appears to inhibit proliferation of cancer cells, its mechanism of action has not been studied in detail. The purpose of this study was to investigate the anti-proliferative effects of 2,4-bis (p-hydroxyphenyl)-2-butenal (HPB242) on two oral squamous cell carcinoma (OSCC) cell lines, HN22 and HSC4, through regulation of specificity protein 1 (Sp1). HPB242 treatment dramatically reduced the cell growth rate and apoptotic cell morphologies. Sp1 was significantly inhibited by HPB242 in a dose-dependent manner. Furthermore, cell cycle regulating proteins and anti-apoptotic proteins, which are known as Sp1 target genes, were altered at the molecular levels. The key important regulators in the cell cycle such as p27, Cyclin D1, myeloid leukemia sequence 1 (Mcl-1) and Survivin were up-regulated by HPB242 or suppressed Sp1 levels, whereas pro-apoptotic proteins caspase3 and PARP were cleaved in HN22 and HSC4. HPB242 may be useful as a chemotherapeutic agent for OSCC for the purpose of treatment and prevention of oral cancer and for the improvement of clinical outcomes.
    Journal of Biomedical Science 01/2014; 21(1):4. DOI:10.1186/1423-0127-21-4 · 2.74 Impact Factor
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    ABSTRACT: Isoprenoid and branched glycerol dialkanol diethers (iGDDs and bGDDs) have recently been found in marine and peat deposits, whereas their distribution and sources in soils are undetermined. We present the distributional characteristics of GDDs as well as their corresponding glycerol dialkyl glycerol tetraethers (GDGTs) in Chinese surface soils and a loess-paleosol sequence (LPS) in northwest China to study the source of GDDs and their relationship with GDGTs. The distributions of iGDDs and bGDDs are comparable with those of the corresponding GDGTs, with a dominance of iGDGTs over bGDGTs in alkaline soil and the opposite in acid soil. By extension, the GDD- and GDGT-based BIT indices exhibit the same trends in both surface soils and the LPS. The fractional abundances of individual iGDDs and bGDDs are also similar to those of the corresponding GDGTs, resulting in similar cyclization patterns for iGDGTs and iGDDs, and similar methylation indices for bGDGTs and bGDDs. These similarities indicate that bGDDs and iGDDs may share a common biological source with their corresponding GDGTs. In the LPS, the GDGT/(GDGT+GDD) ratio decreases exponentially with increased depth, which fits a first order kinetic degradation (or more specifically, transformation) model that has commonly been applied to other lipid classes; this is strong evidence for a diagenetic origin for GDDs. Although our results do not exclude production of GDDs directly by microorganisms, they do suggest that the GDDs may be the degradation products of GDGTs.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 11/2013; 63. DOI:10.1016/j.fct.2013.11.004 · 2.61 Impact Factor
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    ABSTRACT: Pin1, a conserved eukaryotic Peptidyl-prolyl cis/trans isomerase, has profound effects on numerous key-signaling molecules, and its deregulation contributes to disease, particularly cancer. Although Pin1-mediated prolyl isomerization is an essential and novel regulatory mechanism for protein phosphorylation, little is known about the upstream signaling pathway(s) that regulates Pin1 activity. Here, we identify MAP3K-related serine-threonine kinase (the gene encoding COT/Tpl2) as a kinase responsible for phosphorylation of Pin1 Ser16. COT interacts with and phosphorylates Pin1 on Ser16. Consequently, Pin1 Ser16 phosphorylation by COT increases cyclin D1 abundance and enhances tumorigenecity of MCF7 cells. In contrast, depletion of COT in MCF7 cells leads to downregulation of Pin1 Ser16 phosphorylation, which subsequently decrease cyclin D1 levels, inhibiting tumorigenecity of MCF7 cells. In a xenograft model, treatment of TKI, a COT inhibitor, and Juglone, a Pin1 inhibitor, abrogates tumor growth. In human breast cancer patients, immunohistochemical staining shows that Pin1 pSer16 levels are positively correlated with COT levels, providing strong evidence for an essential role of the COT/Pin1 axis in conveying oncogenic signals to promote aggressiveness in human breast cancer. © 2013 Wiley Periodicals, Inc.
    Molecular Carcinogenesis 11/2013; 54(6). DOI:10.1002/mc.22112 · 4.77 Impact Factor
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    ABSTRACT: The overexpression of wild-type cysteine-rich 61 (Cyr61) is associated with the aggressiveness of cancer and poor prognosis in different human cancers. The aim of this study was to examine the expression of Cyr61 protein in prostate adenocarcinomas and to investigate the effects of inhibiting Cyr61 expression using small interfering RNA on the proliferation, migration, invasiveness, and sensitivity of prostate carcinoma PC-3 cells to TNF-related apoptosis-inducing ligand. Cell proliferation was measured by XTT assay. Colony formation assay, wound healing assay, and Matrigel invasion assay were also examined. Immunohistochemical staining of prostate tumor tissues showed that prostate carcinomas had significantly increased Cyr61 level compared with benign glands adjacent to carcinoma. siRNA-based knockdown of Cyr61 resulted in decreased cellular proliferation, clonogenicity, migration, and invasion. At the same time, Cyr61 silencing effectively reduced the levels of phosphorylated Akt and integrin-β3. Cyr61-specific siRNA combined with TRAIL increased the apoptosis of PC-3 cells and the cleavage of apoptosis hallmarkers such as PARP and caspase-3. Taken together, our data provide evidence that Cyr61 modulates integrin-β3 level as well as PI3-kinase/Akt activity through which Cyr61 may mediate tumorigenesis, and suggest the potential importance of Cyr61 targeting on enhancing the therapeutic efficacy of prostate cancer.
    Animal cells and systems the official publication of the Zoological Society of Korea 10/2013; 17(5):306-314. DOI:10.1080/19768354.2013.830647 · 0.35 Impact Factor
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    ABSTRACT: Honokiol (HK), a novel plant-derived natural product, is a physiologically activated compound with polyphenolic structure, and has been identified to function as an anticancer agent. It has been widely used in several diseases as a traditional medicine for a long time. We investigated whether HK could show anticancer effects on two oral squamous cell lines (OSCCs), HN-22 and HSC-4. We demonstrated that HK-treated cells showed dramatic reduction in cell growth and apoptotic cell morphologies. Intriguingly, the transcription factor specificity protein 1 (Sp1) was significantly inhibited by HK in a dose-dependent manner. Furthermore, we checked changes in cell cycle regulatory proteins and anti-apoptotic proteins at the molecular level, which are known as Sp1 target genes. The important key regulators in the cell cycle such as p27 and p21 were up-regulated by HK-mediated down-regulation of Sp1, whereas anti-apoptotic proteins including Mcl-1 and survivin were decreased, resulting in caspase-dependent apoptosis. Taken together, results from this study suggest that HK could modulate Sp1 transactivation and induce apoptotic cell death through the regulation of cell cycle and suppression of anti‑apoptotic proteins. In addition, HK may be used in cancer prevention and therapies to improve the clinical outcome as an anticancer drug.
    International Journal of Oncology 07/2013; 43(4). DOI:10.3892/ijo.2013.2028 · 2.77 Impact Factor

Publication Stats

557 Citations
200.05 Total Impact Points


  • 2013–2015
    • Mokpo National University
      • • Department of Pharmacy
      • • College of Pharmacy
      Mokuho, Jeollanam-do, South Korea
  • 2007–2015
    • University of Minnesota Duluth
      • College of Pharmacy
      Duluth, Minnesota, United States
  • 2011–2013
    • Soonchunhyang University
      • College of Medicine
      Onyang, South Chungcheong, South Korea
  • 2007–2012
    • Konkuk University
      • Department of Bioscience and Technology
      Sŏul, Seoul, South Korea
  • 2009–2011
    • Chonbuk National University
      Tsiuentcheou, Jeollabuk-do, South Korea
    • Molecular and Cellular Biology Program
      • Department of Molecular and Cellular Biology
      Seattle, Washington, United States
  • 2008–2010
    • Chosun University
      • College of Pharmacy
      Goyang, Gyeonggi, South Korea
  • 2005
    • Korea Research Institute of Bioscience and Biotechnology KRIBB
      • Laboratory of Cell Biology
      Anzan, Gyeonggi Province, South Korea