Jung-Hyun Shim

Mokpo National University, Mokuho, South Jeolla, South Korea

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Publications (52)161.07 Total impact

  • Ka Hwi Kim, Goo Yoon, Jung Jae Cho, Jin Hyoung Cho, Young Sik Cho, Jung-Il Chae, Jung-Hyun Shim
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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;
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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; · 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; · 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; · 1.74 Impact Factor
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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;
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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; · 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; · 1.75 Impact Factor
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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; · 5.07 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. · 2.74 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; · 4.27 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; · 2.99 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; · 2.77 Impact Factor
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    ABSTRACT: Inhibitors of histone deacetylases (HDACs) represent a novel class of therapeutic anticancer agents. Panobinostat (LBH589) induces apoptosis through the regulation of specificity protein 1 (Sp1) in the oral squamous cell carcinoma (OSCC) cell lines, HN22 and HSC4. In this study, we analyzed the underlying signaling pathways and the mechanisms involved in this process by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, 4',6-diamidino-2-phenylindole (DAPI) staining, immunocytochemistry and western blot analysis. LBH589 significantly reduced cell growth and the sub-G1 cell population and induced apoptosis. Sp1 protein expression was significantly reduced following treatment with LBH589 in a concentration-dependent manner. Furthermore, LBH589 upregulated the expression of p27 and p21 and downregulated the expression of cyclin D1, myeloid cell leukemia-1 (Mcl-1) and survivin; this led to the activation of apoptotic signaling pathways through the increase of Bax expression and the decrease of Bid and Bcl-xL expression. Treatment with LBH589 also induced the cleavage of caspase‑3 and PARP in the HN22 and HSC4 cells. Taken together, our data demonstrate that LBH589 induces the apoptosis of OSCC cells by suppressing Sp1 expression, indicating that LBH589 may be a promising chemotherapeutic agent for the treatment of OSCC.
    International Journal of Molecular Medicine 07/2013; · 1.88 Impact Factor
  • Jung-Il Chae, Young-Joo Jeon, Jung-Hyun Shim
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    ABSTRACT: Malignant pleural mesothelioma (MPM) is an extremely aggressive type of cancer and is associated with a poor patient prognosis due to its rapid progression. Novel therapeutic agents such as honokiol (HNK) improve the clinical outcomes of cancer therapy, yet the mechanisms involved have not been fully elucidated. The present study examined the regulatory effects of HNK on the growth and apoptosis of MSTO-211H mesothelioma cells and investigated its anticancer mechanism. The results revealed that HNK significantly reduced the cell viability and increased the sub-G1 population in MSTO-211H cells and suppressed the expression of the specificity protein 1 protein (Sp1). HNK reduced the transcriptional activity of Sp1 regulatory proteins, including cyclin D1, Mcl-1 and survivin, and, thus, induced apoptosis signaling pathways by increasing Bax, reducing Bid and Bcl-xl and activating caspase-3 and PARP in mesothelioma cells. The results suggest that Sp1, a novel molecular target of HNK, may be related to cell cycle arrest and apoptosis induction through the modulation of signal transduction pathways in MPM.
    Oncology Reports 03/2013; · 2.19 Impact Factor
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    ABSTRACT: The Maillard reaction is a chemical reaction occurring between an amino acid and a reducing sugar, usually requiring thermal processing. Maillard reaction products (MRPs) have antioxidant, antimutagenic, and antibacterial effects, and although 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. We found that HPB242 treatment modulated expression of cyclins and tumor suppressor genes in SiHa human cervical cancer cell lines: cyclins and phospho-pRB were downregulated, whereas the expression of CDK inhibitors and p53 was enhanced. HPB242 induced apoptosis dose-dependently by suppressing E7 expression and leading to sub-G1 cell-cycle arrest in SiHa cell lines; treatment also led to the proteolytic cleavage of caspase-3, -9, and poly (ADP-ribose) polymerase. Moreover, HPB242 upregulated Fas expression, altered expressions of pro- and antiapoptotic factors, and also inhibited nuclear translocation of nuclear factor κB and phosphorylation of IκB. HPB242 treatment decreased phosphatidyl inositol-3 kinase and p-Akt expression levels, demonstrating that this survival pathway may also be inhibited by HPB242. Cumulatively, HPB242 promotes apoptosis by influencing E7 expression, inducing cell-cycle arrest at sub-G1 phase, and promoting both intrinsic (mitochondrial) and extrinsic (Fas-dependent) apoptosis in SiHa human cervical cancer cells.
    Nutrition and Cancer 11/2012; 64(8):1236-44. · 2.70 Impact Factor
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    ABSTRACT: Quercetin (Qu) is found in plants, including red onions and in the skins of red apples, and induces the apoptosis of certain malignant cells. However, no report has been issued on the apoptotic effect of Qu on human malignant pleural mesothelioma. In the present study, it was found that MSTO‑211H mesothelioma cell viability was reduced and apoptotic cell death was increased by Qu (20-80 µM), which was found to have an IC50 of 58 µM. In addition, Qu increased the sub-G1 cell population, and was found to interact with specificity protein 1 (Sp1) and significantly suppressed its expression at the protein and mRNA levels. Furthermore, Qu modulated the levels of Sp1 regulatory genes, such as cyclin D1, myeloid cell leukemia (Mcl)-1 and survivin in MSTO-211H cells. Apoptotic signaling cascades were activated by the cleavage of Bid, caspase-3 and PARP, and by the downregulation of Bcl-xL and the upregulation of Bax in MSTO-211H cells. Our results strongly suggest that Sp1 be considered as a novel molecular target of Qu in human malignant pleural mesothelioma.
    International Journal of Molecular Medicine 07/2012; · 1.88 Impact Factor
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    ABSTRACT: For thousands of years in Asia, Althaea rosea Cavanil (ARC) and Plantago major L. (PML) have been used as powerful non-toxic therapeutic agents that inhibit inflammation. However, the anticancer mechanisms and molecular targets of ARC and PML are poorly understood, particularly in epidermal growth factor (EGF)-induced neoplastic cell transformation. The aim of this study was to evaluate the chemopreventive effects and mechanisms of the methanol extracts from ARC (MARC) and PML (MPML) in EGF-induced neoplastic cell transformation of JB6 P+ mouse epidermal cells using an MTS assay, anchorage-independent cell transformation assay and western blotting. Our results showed that MARC and MPML significantly suppressed neoplastic cell transformation by inhibiting the kinase activity of the EGF receptor (EGFR). The activation of EGFR by EGF was suppressed by MARC and MPML treatment in EGFR(+/+) cells, but not in EGFR(-/-) cells. In addition, MARC and MPML inhibited EGF-induced cell proliferation in EGFR-expressing murine embryonic fibroblasts (EGFR(+/+)). These results strongly indicate that EGFR targeting by MARC and MPML may be a good strategy for chemopreventive or chemotherapeutic applications.
    Molecular Medicine Reports 07/2012; 6(4):843-7. · 1.48 Impact Factor
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    Kyung-Ae Lee, Jung-Il Chae, Jung-Hyun Shim
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    ABSTRACT: Malignant pleural mesothelioma (MPM) is a highly aggressive cancer with a very poor prognosis. Several clinical studies such as immunotherapy, gene therapy and molecular targeting agents have been tried for treatment of malignant mesothelioma, however, there is no application for effective clinical treatment. Coffee has various biological functions such as anti-oxidant, anti-inflammatory, anti-mutagenic and anti-carcinogenic activities. The therapeutic activities of the bioactive compounds in coffee was sugested to influence intracellular signaling of MPM. Regarding to the cancer-related functions, In this study, suppression of Sp1 protein level followed by induction of MSTO-211H cell apoptosis by cafestol and kahweol were investigated in oreder to determine Sp1's potential as a significant target for human MPM therapy as well. Cells were treated separately with final concentration of cafestol and kahweol and the results were analyzed by MTS assay, DAPI staining, PI staining, luciferase assay, RT-PCR, and immunoblotting. Viability of MSTO-211H and H28 cells were decreased, and apoptotic cell death was increased in MSTO-211H as a result of cafestol and kahweol treatment. Cafestol and kahweol increased Sub-G1 population and nuclear condensation in MSTO-211H cells. Roles of Sp1 in cell proliferation and apoptosis of the MSTO-211H cells by the Sp1 inhibitor of Mithramycin A were previously confirmed. Cafestol and kahweol significantly suppressed Sp1 protein levels. Kahweol slightly attenuated Sp1 mRNA, while Cafestol did not affect in MSTO-211H cells. Cafestol and kahweol modulated the promoter activity and protein expression level of the Sp1 regulatory genes including Cyclin D1, Mcl-1, and Survivin in mesothelioma cells. Apoptosis signaling cascade was activated by cleavages of Bid, Caspase-3, and PARP with cafestol and by upregulation of Bax, and downregulation of Bcl-xl by kahweol. Sp1 can be a novel molecular target of cafestol and kahweol in human MPM.
    Journal of Biomedical Science 06/2012; 19:60. · 2.74 Impact Factor
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    ABSTRACT: BACKGROUND: The aims of this study were to evaluate the apoptotic activities and molecular mechanisms of methanol extracts of Dianthus chinensis (MEDC) and Acalypha australis L. (MEAL) in human oral cancer cells. METHODS: The apoptotic effects and related molecular mechanisms of MEDC and MEAL on oral cancer cells were evaluated using MTS assay, DAPI staining, immunostaining, Western blotting, and reverse transcriptase-polymerase chain reaction. RESULTS: Sp1 was overexpressed in oral tumor tissues compared with normal oral mucosa. Downregulation of Sp1 inhibited the growth of SCC-15 and YD-15 oral cancer cells. MEDC and MEAL inhibited cell growth and induced apoptosis in both cell lines by decreasing the expression of Sp1. In addition, treatment of cells with MEDC and MEAL decreased Mcl-1 expression, which is a downstream target of Sp1. CONCLUSION: Our results indicate that MEDC and MEAL are bioactive natural products that can potentially induce apoptosis of tumor cells that overexpress the Sp1 protein. © 2012 Wiley Periodicals, Inc. Head Neck, 2012.
    Head & Neck 06/2012; · 2.83 Impact Factor
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    ABSTRACT: Post-translational modification of peptidyl cis/trans prolyl isomerase Pin1 is crucial in regulation of gene stability. Pin1 phosphorylation at Ser(16) has been regarded as a marker for Pin1 isomerase activity and introduction of phosphorylation on Ser/Thr-Pro of substrate proteins is prerequisite for its binding activity with Pin1 and subsequent isomerization. Here, we found that 90 kDa ribosomal protein S6 kinase 2 (RSK2) could form a physical complex with Pin1, leading to phosphorylation of Pin1 at Ser(16) ex vivo and in vitro respectively. Intriguingly, Pin1(+/+) mouse embryonic fibroblasts (MEFs) exhibited significantly an increase in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced RSK2 phosphorylation with a marginal Pin1 phosphorylation compared with Pin1(-/-) MEFs. Moreover, TPA-induced Ser(16) Pin1 phosphorylation as well as RSK2 phosphorylation was considerably profound in RSK(+/+) MEFs but not in RSK(-/-) MEFs. Consequently, knockdown of Pin1 using shRNA-Pin1 suppressed TPA-induced cell transformation in JB6 CI41 cells. Overall, these results indicate that Pin1 plays a critical role in TPA-induced tumorigenesis plausibly via physical interaction with RSK2 and reciprocal phosphorylation, therefore suggesting a potential therapeutic target for cancer treatment.
    Molecular and Cellular Biochemistry 05/2012; 367(1-2):85-92. · 2.39 Impact Factor

Publication Stats

439 Citations
161.07 Total Impact Points

Institutions

  • 2013–2014
    • Mokpo National University
      • College of Pharmacy
      Mokuho, South Jeolla, South Korea
  • 2009–2013
    • Chonbuk National University
      • Department of Animal Science
      Sŏul, Seoul, South Korea
  • 2008–2013
    • Chosun University
      • College of Pharmacy
      Gwangju, Gwangju, South Korea
  • 2012
    • Keimyung University
      • Department of Pharmacy
      Seoul, Seoul, South Korea
  • 2007–2012
    • Konkuk University
      • Department of Bioscience and Technology
      Sŏul, Seoul, South Korea
  • 2011
    • Soonchunhyang University
      • College of Medicine
      Onyang, South Chungcheong, South Korea
  • 2007–2011
    • University of Minnesota Duluth
      Duluth, Minnesota, United States
  • 2004–2005
    • Korea Research Institute of Bioscience and Biotechnology KRIBB
      • • Laboratory of Cell Biology
      • • Laboratory of Cellular Biology
      Ansan, Gyeonggi, South Korea