Byong Chul Yoo

National Cancer Center Korea, Kōyō, Gyeonggi Province, South Korea

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Publications (53)192.55 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Gouania leptostachya DC. var. tonkinensis Pitard. Rhamnaceae is a traditional medicinal plant used in Thailand for treating various inflammatory symptoms. However, no systematic studies have been performed concerning the anti-inflammatory effects or molecular mechanisms of this plant. The immunopharmacological activities of a methanol extract from the leaves and twigs of G. leptostachya (Gl-ME) were elucidated based on the gastritis symptoms of mice treated with HCl/EtOH and the inflammatory responses, such as nitric oxide (NO) release and prostaglandin E2 (PGE2 ) production, from RAW264.7 cells and peritoneal macrophages. Moreover, inhibitory target molecules were also assessed. Gl-ME dose-dependently diminished the secretion of NO and PGE2 from LPS-stimulated RAW264.7 cells and peritoneal macrophages. The gastritis lesions of HCl/EtOH-treated mice were also attenuated after Gl-ME treatment. The extract (50 and 300 µg/mL) clearly reduced mRNA expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2, nuclear translocation of p65/nuclear factor (NF)-κB, phosphorylation of p65-activating upstream enzymes, such as protein kinase B (AKT), inhibitor of κBα kinase (IKK), and inhibitor of κB (IκBα), and the enzymatic activity of Src. By HPLC analysis, one of the major components in the extract was revealed as resveratrol with NO and Src inhibitory activities. Moreover, this compound suppressed NO production and HCl/EtOH-induced gastric symptoms. Therefore, these results suggest that Gl-ME might be useful as an herbal anti-inflammatory medicine through the inhibition of Src and NF-κB activation pathways. The efficacy data of G. leptostachya also implies that this plant could be further tested to see whether it can be developed as potential anti-inflammatory preparation. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.
    Phytotherapy research : PTR. 11/2014;
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    ABSTRACT: To perform chemoradiotherapy (CRT) effectively, it is clinically beneficial to identify predictors of tumor response after CRT. This study examined the association between plasma fibrinogen level before preoperative CRT and tumor response in advanced rectal cancer.
    Annals of Surgical Oncology 11/2014; · 4.12 Impact Factor
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    Mi-Yeon Kim, Byong Chul Yoo, Jae Youl Cho
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    ABSTRACT: Background Ginsenoside Rp1 (G-Rp1) is a novel ginsenoside derived from ginsenoside Rk1. This compound was reported to have anti-cancer, anti-platelet, and anti-inflammatory activities. In this study, we examined the molecular target of G-Rp1’s anti-proliferative and pro-apoptotic activities. Methods To examine the effects of G-Rp1, cell proliferation assays, propidium iodine staining, proteomic analysis by two-dimensional gel electrophoresis, immunoblotting analysis, and a knockdown strategy were employed. Results G-Rp1 dose-dependently suppressed the proliferation of colorectal cancer LoVo cells and also increased the apoptosis of these cells. Interestingly, G-Rp1 remarkably up-regulated the protein level of apolipoprotein (Apo)-A1 in LoVo, SNU-407, DLD-1, SNU-638, AGS, KPL-4, and SK-BR-3 cells. The knockdown of Apo-A1 by its siRNA increased the levels of cleaved poly(ADP-ribose) polymerase (c-PARP) and p53 and diminished the proliferation of LoVo cells. Conclusion These results suggest that G-Rp1 may act as an anti-cancer agent by strongly inhibiting cell proliferation and enhancing cell apoptosis through the up-regulation of Apo-A1.
    Journal of ginseng research 10/2014; · 2.26 Impact Factor
  • Kun Kim, Seung-Gu Yeo, Byong Chul Yoo
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    ABSTRACT: Patients show variable responses to chemoradiotherapy (CRT), which is generally administered before surgery for locally advanced rectal cancer (LARC). The aim of this study was to identify molecular markers predictive of CRT responses by analysis of low-mass ions (LMIs) in serum of LARC patients.
    Cancer research and treatment : official journal of Korean Cancer Association. 08/2014;
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    ABSTRACT: Introduction The purpose of this study was the development of 68Ga-labeled neolactosylated human serum albumin (LSA) for imaging asialoglycoprotein receptors in the liver by using positron emission tomography (PET), which would enable functional imaging with higher resolution than single-photon emission computed tomography (SPECT). Methods LSA was synthesized by conjugating α-lactose to human serum albumin (HSA) by reductive amination. LSA was conjugated with 2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (SCN-NOTA) and the resultant NOTA-LSA was labeled with 68Ga at room temperature. The labeling efficiency of NOTA-LSA was evaluated as a function of pH and time. The stability of 68Ga-NOTA-LSA in phosphate buffered saline (PBS) and human serum at 37 °C was determined. Biodistribution and PET studies of 68Ga-NOTA-LSA were performed in mice following tail vein injection of radiotracer. Results The numbers of lactose and NOTA units per HSA were determined to be 31.7 and 4.6, respectively. When the reaction was done at room temperature, the labeling efficiency of NOTA-LSA was higher than 99% at pH 4.8 and 96% at pH 6. More than 95% of the detected radioactivity was associated with the intact molecule for at least the 4 h following synthesis when incubated in PBS or human serum at 37 °C. Biodistribution and animal PET studies showed specific retention of 68Ga-NOTA-LSA in liver following intravenous administration. Conclusion 68Ga-NOTA-LSA was successfully developed for imaging asialoglycoprotein receptors in the liver with a simple labeling method, high labeling efficiency, and high stability.
    Nuclear Medicine and Biology 08/2014; · 2.52 Impact Factor
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    ABSTRACT: Ovarian cancer (OVC) is one of the most difficult types of cancer to detect in the early stages of its development. There have been numerous attempts to identify a biomarker for OVC; however, an accurate diagnostic marker has yet to be identified. The present study profiled OVC candidate metabolites from the serum to identify potential diagnostic markers for OVC. Data regarding low-mass ions (LMIs) in the serum were obtained using matrix-assisted laser desorption/ionization (MALDI)-time-of-flight analysis. MALDI-mass spectrometry (MS) analysis of each serum sample was repeated six times in order to reduce the likelihood of experimental errors. The intensity of the LMI mass peaks were normalized using total peak area sums. The normalized intensity of LMI was used in principal component analysis-discriminant analysis to differentiate between 142 patients with OVC and 100 healthy control participants. Liquid chromatography-MS/MS was used to identify the selected LMIs. Extracted ion chromatogram analysis was used to measure the relative quantity of candidate metabolites from the LMI mass peak areas. The concentration of common metabolites in the serum was determined using ELISA. The top 20 LMI mass peaks with a weigh factor over 0.05 were selected to distinguish between the patients with OVC and the controls. Among the LMIs, two with 184.05 and 496.30 m/z were identified as L-homocysteic acid (HCA) and lysophosphatidylcholine (LPC) (16:0), respectively. The relative quantity of LPC (16:0) was found to be decreased in the OVC serum (P=0.05), while the quantity of HCA was observed to be significantly higher in the OVC serum (P<0.001). HCA was not detected in 59 cases out of the 63 control participants; however, the majority of the cases of OVC (16/25) exhibited significantly higher quantities of HCA. When the cutoff was 10 nmol/ml, the sensitivity and specificity of HCA were 64.0 and 96.9%, respectively. The level of LPC (16:0) was significantly correlated with tumor grade (P=0.045). HCA and LPC (16:0) showed correlation with stage and tumor histology, but the limited sample size resulted in a lack of statistical significance. The findings of the present study suggest that HCA may have potential to be a biomarker for OVC. The stratified screening including LPC (16:0) did not significantly increase the power for OVC screening; however, the present study showed that profiling LMIs in serum may be useful for identifying candidate metabolites for OVC screening.
    Oncology letters 08/2014; 8(2):566-574. · 0.24 Impact Factor
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    ABSTRACT: Resistance to 5-fluorouracil (5-FU) in patients with colorectal cancer prevents effective treatment and leads to unnecessary and burdensome chemotherapy. Therefore, prediction of 5-FU resistance is imperative. To identify the proteins linked to 5-FU resistance, two-dimensional gel electrophoresis-based proteomics was performed using the human colon cancer cell line SNU-C4R with induced 5-FU resistance. Proteins showing altered expression in SNU-C4R were identified by matrix-associated laser desorption/ionization-time-of-flight analysis, and their roles in susceptibility to 5-FU or radiation were evaluated in various cell lines by transfection of specific siRNA or creation of overexpression constructs. Changes in cellular signaling and expression of mitochondrial apoptotic factors were investigated by Western Blot analysis. A mitochondrial membrane potential probe (JC-1 dye) and a flow cytometry system were employed to determine the mitochondrial membrane potential. Finally, protein levels were determined by Western Blot analysis in tissues from 122 patients with rectal cancer to clarify whether each identified protein is a useful predictor of a chemoradiation response. We identified mitochondrial phosphoenolpyruvate carboxykinase (mPEPCK) as a candidate predictor of 5-FU resistance. PEPCK was downregulated in SNU-C4R compared with its parent cell line SNU-C4. Overexpression of mPEPCK did not significantly alter the susceptibility to either 5-FU or radiation. Suppression of mPEPCK led to a decrease in both the cellular level of phosphoenolpyruvate and the susceptibility to 5-FU and radiation. Furthermore, the cellular levels of phosphoenolpyruvate (an end product of PEPCK and a substrate of pyruvate kinase), phosphorylated AKT, and phosphorylated 4EBP1 were decreased significantly secondary to the mPEPCK suppression in SNU-C4. However, mPEPCK siRNA transfection induced changes in neither the mitochondrial membrane potential nor the expression levels of mitochondrial apoptotic factors such as Bax, Bcl-2, and Bad. Downregulation of total PEPCK was observed in tissues from patients with rectal cancer who displayed poor responses to preoperative 5-FU-based radiation therapy. Our overall results demonstrate that mPEPCK is a useful predictor of a response to chemoradiotherapy in patients with rectal cancer.
    BMC Cancer 03/2014; 14(1):160. · 3.33 Impact Factor
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    ABSTRACT: The aim of this study was to investigate whether profiling metabolic compounds in human colon cancer cells with induced 5-florouracil resistance enables identification of predictive biomarkers for 5-florouracil resistance.
    Hepato-gastroenterology 03/2014; 61(130):343-8. · 0.77 Impact Factor
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    ABSTRACT: Numerous derivatives of kojic acid have been synthesised to expand its immunopharmacological uses. Kojic acid is known to have anti-cancer, anti-inflammatory, and anti-melanogenesis effects. We found that (5-hydroxy-4-oxo-4H-pyran-2-yl)methyl 6-hydroxynaphthalene-2-carboxylate (MHNC) strongly suppressed the production of nitric oxide (NO) in an initial screening experiment. In this study, we explored the in vitro and in vivo anti-inflammatory activity of MHNC and its inhibitory mechanisms using lipopolysaccharide (LPS)-treated RAW264.7 cells and HCl/EtOH-treated ICR mice. MHNC dose-dependently diminished the secretion of nitric oxide (NO) and prostaglandin (PG)E2 in LPS-treated RAW264.7 cells. This compound also suppressed the upregulation of mRNA levels for the inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 genes. Additionally, the transcriptional activation of these genes was inhibited by MHNC through the suppression of the nuclear translocation of nuclear factor (NF)-κB subunits (p65 and p50), as determined by a luciferase reporter assay. Interestingly, MHNC treatment was found to suppress a series of upstream signalling cascades consisting of IκBα, AKT, PDK1, Src, and Syk for NF-κB activation. Furthermore, a direct enzyme assay with purified Src and Syk and luciferase assays using Src and Syk overexpression indicated that these enzymes were directly inhibited by MHNC. Finally, MHNC (20mg/kg) prevented inflammatory symptoms of the stomach in mice treated with HCl/EtOH by reducing phospho-IκBα levels. Taken together, our data suggest that MHNC may negatively modulate in vitro and in vivo inflammatory responses via the direct suppression of Syk/Src and NF-κB.
    International immunopharmacology 02/2014; · 2.21 Impact Factor
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    ABSTRACT: Inflammation is a natural host defensive process that is largely regulated by macrophages during the innate immune response. Mitogen-activated protein kinases (MAPKs) are proline-directed serine and threonine protein kinases that regulate many physiological and pathophysiological cell responses. p38 MAPKs are key MAPKs involved in the production of inflammatory mediators, including tumor necrosis factor- α (TNF- α ) and cyclooxygenase-2 (COX-2). p38 MAPK signaling plays an essential role in regulating cellular processes, especially inflammation. In this paper, we summarize the characteristics of p38 signaling in macrophage-mediated inflammation. In addition, we discuss the potential of using inhibitors targeting p38 expression in macrophages to treat inflammatory diseases.
    Mediators of Inflammation 01/2014; 2014:352371. · 3.88 Impact Factor
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    ABSTRACT: Activating transcription factor 2 (ATF2) is a member of the leucine zipper family of DNA-binding proteins and is widely distributed in tissues including the liver, lung, spleen, and kidney. Like c-Jun and c-Fos, ATF2 responds to stress-related stimuli and may thereby influence cell proliferation, inflammation, apoptosis, oncogenesis, neurological development and function, and skeletal remodeling. Recent studies clarify the regulatory role of ATF2 in inflammation and describe potential inhibitors of this protein. In this paper, we summarize the properties and functions of ATF2 and explore potential applications of ATF2 inhibitors as tools for research and for the development of immunosuppressive and anti-inflammatory drugs.
    Mediators of Inflammation 01/2014; 2014:950472. · 3.88 Impact Factor
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    ABSTRACT: Current fecal screening tools for colorectal cancer (CRC), such as fecal occult blood tests (FOBT), are limited by their low sensitivity. Calgranulin B (CALB) was previously reported as a candidate fecal marker for CRC. This study investigated whether a combination of the FOBT and fecal CALB has increased sensitivity and specificity for a diagnosis of CRC.
    PLoS ONE 01/2014; 9(9):e106182. · 3.53 Impact Factor
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    ABSTRACT: Cancer stem cells (CSCs) are known to be resistant to conventional chemotherapy and radiotherapy. Specific CSC targeting and eradication is therefore a therapeutically important challenge. CD133 is a colorectal CSC marker with unknown function(s). Assessing proteomic changes induced by CD133 may provide clues not only to new CD133 functions but also to the chemotherapy and radiation susceptibility of colon cancer cells. To identify the proteins affected by CD133, CD133-positive (CD133+), and CD133-negative (CD133-) human colon cancer cells were obtained by cell sorting. Whole proteomes were profiled from SW620/CD133+ and SW620/CD133- cells and analyzed by 2D-based proteome analysis. Nucleophosmin (NPM1) was identified as a protein regulated by CD133. CD133 protein level was not affected by NPM1, and an interaction between the two proteins was not observed. CD133 and NPM1 protein levels were positively correlated in 11 human colon cancer cell lines. The CD133+ subpopulation percentage or its value normalized against CD133 protein level was only linked to intrinsic susceptibility of human colon cancer cells to 5-fluorouracil (5-FU). However, either suppression of CD133 or NPM1 significantly increased 5-FU susceptibility of SW620. The present study suggests that CD133-regulated NPM1 protein level may provide a clue to novel CD133 function(s) linked to human colon cancer cell susceptibility to chemotherapy.
    Electrophoresis 11/2013; · 3.26 Impact Factor
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    ABSTRACT: Blood metabolites can be detected as low-mass ions (LMIs) by mass spectrometry (MS). These LMIs may reflect the pathological changes in metabolism that occur as part of a disease state, such as cancer. We constructed a LMI discriminant equation (LOME) to investigate whether systematic LMI profiling might be applied to cancer screening. LMI information including m/z and mass peak intensity was obtained by five independent MALDI-MS analyses, using 1,127 sera collected from healthy individuals and cancer patients with colorectal cancer (CRC), breast cancer (BRC), gastric cancer (GC) and other types of cancer. Using a two-stage principal component analysis to determine weighting factors for individual LMIs and a two-stage LMI selection procedure, we selected a total of 104 and 23 major LMIs by the LOME algorithms for separating CRC from control and rest of cancer samples, respectively. CRC LOME demonstrated excellent discriminating power in a validation set (sensitivity/specificity; 93.21%/96.47%). Furthermore, in a fecal occult blood test (FOBT) of available validation samples, the discriminating power of CRC LOME was much stronger (sensitivity/specificity; 94.79%/97.96%) than that of the FOBT (sensitivity/specificity; 50.00%/100.0%), which is the standard CRC screening tool. The robust discriminating power of the LOME scheme was reconfirmed in screens for BRC (sensitivity/specificity; 92.45%/96.57%) and GC (sensitivity/specificity; 93.18%/98.85%). The present study demonstrates that LOMEs might be powerful non-invasive diagnostic tools with high sensitivity/specificity in cancer screening. The use of LOMEs could potentially enable screening for multiple diseases (including different types of cancer) from a single sampling of LMI information. © 2013 Wiley Periodicals, Inc.
    International Journal of Cancer 10/2013; · 6.20 Impact Factor
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    ABSTRACT: Adenosine dialdehyde (AdOx) inhibits transmethylation by the accumulation of S-adenosylhomocysteine (SAH), a negative feedback inhibitor of methylation, through the suppression of SAH hydrolase (SAHH). In this study, we aimed to determine the regulatory effect of AdOx on cancer invasion by using three different cell lines: MDA-MB-231, MCF-7, and U87. The invasive capacity of these cells in the presence (MCF-7) or absence (MDA-MB-231 and U87) of phorbal 12-myristate 13-actate (PMA) was strongly decreased by AdOx treatment. Furthermore, the expression, secretion, and activation of matrix metalloproteinase (MMP)-9, a critical enzyme regulating cell invasion, in these cells were diminished by AdOx treatment. AdOx strongly suppressed AP-1-mediated luciferase activity and, in parallel, reduced the translocation of c-Fos and c-Jun into the nucleus. AdOx was shown to block a series of upstream AP-1 activation signaling complexes composed of extracellular signal-related kinase (ERK), mitogen-activated protein ERK kinase (MEK)1/2, Raf-1, and Ras, as assessed by measuring the levels of the phosphorylated and membrane-translocated forms. Furthermore, we found that suppression of SAHH by siRNA and 3-deazaadenosine, knock down of isoprenylcysteine carboxyl methyltransferase (ICMT), and treatment with SAH showed inhibitory patterns similar to those of AdOx. Therefore, our data suggest that AdOx is capable of targeting the methylation reaction regulated by SAHH and ICMT and subsequently downregulating MMP-9 expression and decreasing invasion of cancer cells through inhibition of the Ras/Raf-1/ERK/AP-1 pathway.
    Biochemical pharmacology 08/2013; · 4.25 Impact Factor
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    ABSTRACT: Renal cell carcinoma (RCC), the predominant form of kidney cancer, is characterized by high resistance to radiation and chemotherapy. This study shows that expression of protein cross-linking enzyme transglutaminase 2 (TGase 2) is markedly increased in 7 renal cell carcinoma (RCC) cell lines in comparison to HEK293 and other cancer cell lines, such as NCI 60. However, the key role of TGase 2 in RCC was not clear. The down-regulation of TGase 2 was found to stabilize p53 expression, thereby inducing a 3- to 10-fold increase in apoptosis for 786-O, A498, CAKI-1, and ACHN cell lines by DAPI staining. MEF cells from TGase 2(-/-) mice showed stabilized p53 under apoptotic stress to compare to MEFs from wild-type mice. TGase 2 directly cross links the DNA binding domain of p53, leading to p53 depletion via autophagy in RCC. TGase 2 and p53 expression showed an inverse relationship in RCC cells. This finding implies that induced expression of TGase 2 promotes tumor cell survival through p53 depletion in RCC.-Ku, B.M., Kim, D.-S. Kim, K.-H., Yoo, B.C., Kim, S.-H., Gong, Y.-D., Kim, S.-Y. Transglutaminase 2 inhibition found to induce p53 mediated apoptosis in renal cell carcinoma.
    The FASEB Journal 05/2013; · 5.70 Impact Factor
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    ABSTRACT: Transmethylation is an important reaction that transfers a methyl group in S-adenosylmethionine (SAM) to substrates such as DNA, RNA, and proteins. It is known that transmethylation plays critical roles in various cellular responses. In this study, we examined the effects of transmethylation on tumorigenic responses and its regulatory mechanism using an upregulation strategy of adenosylhomocysteine (SAH) acting as a negative feedback inhibitor. Treatment with adenosine dialdehyde (AdOx), an inhibitor of transmethylation-suppressive adenosylhomocysteine (SAH) hydrolase (SAHH), enhanced the level of SAH and effectively blocked the proliferation, migration, and invasion of cancer cells; the treatment also induced the differentiation of C6 glioma cells and suppressed the neovascular genesis of eggs in a dose-dependent manner. Through immunoblotting analysis, it was found that AdOx was capable of indirectly diminishing the phosphorylation of oncogenic Src and its kinase activity. Interestingly, AdOx disrupted actin cytoskeleton structures, leading to morphological changes, and suppressed the formation of a signaling complex composed of Src and p85/PI3K, which is linked to various tumorigenic responses. In agreement with these data, the exogenous treatment of SAH or inhibition of SAHH by specific siRNA or another type of inhibitor, 3-deazaadenosine (DAZA), similarly resulted in antitumorigenic responses, suppressive activity on Src, the alteration of actin cytoskeleton, and a change of the colocalization pattern between actin and Src. Taken together, these results suggest that SAH/SAHH-mediated transmethylation could be linked to the tumorigenic processes through cross-regulation between the actin cytoskeleton and Src kinase activity.
    Biochemical pharmacology 01/2013; · 4.25 Impact Factor
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    ABSTRACT: The hydroxylated benzene metabolite hydroquinone (HQ) is mainly generated from benzene, an important industrial chemical, and is also a common dietary component. Although numerous papers have addressed the potential role of HQ in tumorigenic responses, the immunosuppressive and anti-inflammatory effects of hydroquinone have also been considered. In this study, we characterized the mechanism of the induction of hemeoxygenase (HO)-1 and other phase 2 enzymes by HQ and its derivatives. HQ upregulated the mRNA and protein levels of HO-1 by increasing the ARE-dependent transcriptional activation of NRF-2. Src knockdown or deficiency induced via siRNA treatment and infection with a retrovirus expressing shRNA targeting Src as well as exposure to PP2, a Src kinase inhibitor, strongly abrogated HO-1 expression. Interestingly, HQ directly targeted and bound to the sulfhydryl group of Cysteine-483 (C483) and C400 residues of Src, potentially leading to disruption of intracellular disulfide bonds. Src kinase activity was dramatically enhanced by mutation of these Cysteine sites, implying that these sites may play an important role in the regulation of Src kinase activity. Therefore, our data suggest that Src and, particularly, its C483 target site can be considered as prime molecular targets of the HQ-mediated induction of phase 2 enzymes, which is potentially linked to HO-1-mediated cellular responses such as immunosuppressive and anti-inflammatory actions.
    Free Radical Biology and Medicine 01/2013; · 5.27 Impact Factor
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    ABSTRACT: Abstract HangAmDan-B (HAD-B) is a powdered mixture of eight ethnopharmacologically characterized folk medicines that is prescribed for solid masses and cancers in Korea. In view of the finding that macrophage-mediated inflammation is a pathophysiologically important phenomenon, we investigated whether HAD-B modulates inflammatory responses and explored the associated molecular mechanisms. The immunomodulatory activity of HAD-B in toll-like receptor-activated macrophages induced by lipopolysaccharide (LPS) was assessed by measuring nitric oxide (NO) and prostaglandin E(2) (PGE(2)) levels. To identify the specific transcription factors (such as nuclear factor [NF]-κB and signaling enzymes) targeted by HAD-B, biochemical approaches, including kinase assays and immunoblot analysis, were additionally employed. HAD-B suppressed the production of PGE(2) and NO in LPS-activated macrophages in a dose-dependent manner. Furthermore, the extract ameliorated HCl/EtOH-induced gastritis symptoms. Moreover, HAD-B significantly inhibited LPS-induced mRNA expression of inducible NO synthase and cyclooxygenase (COX)-2. Interestingly, marked inhibition of NF-κB and activating transcription factor was observed in the presence of HAD-B. Data from direct kinase assays and immunoblot analysis showed that HAD-B suppresses activation of the upstream signaling cascade involving spleen tyrosine kinase, Src, p38, c-Jun N-terminal kinase, and transforming growth factor β-activated kinase 1. Finally, kaempferol, but not quercetin or resveratrol was identified as a bioactive compound in HAD-B. Therefore, our results suggest that HAD-B possesses anti-inflammatory activity that contributes to its anticancer property.
    Journal of medicinal food 12/2012; · 1.39 Impact Factor
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    ABSTRACT: BACKGROUND: Caldesmon (CaD), a major actin-associated protein, is found in smooth muscle and non-muscle cells. Smooth muscle caldesmon, h-CaD, is a multifunctional protein, and non-muscle cell caldesmon, l-CaD, plays a role in cytoskeletal architecture and dynamics. h-CaD is thought to be an useful marker for smooth muscle tumors, but the role(s) of l-CaD has not been examined in tumors. METHODS: Primary colon cancer and liver metastasis tissues were obtained from colon cancer patients. Prior to chemoradiotherapy (CRT), normal and cancerous tissues were obtained from rectal cancer patients. Whole-tissue protein extracts were analyzed by 2-DE-based proteomics. Expression and phosphorylation level of main cellular signaling proteins were determined by western blot analysis. Cell proliferation after CaD siRNA transfection was monitored by MTT assay. RESULTS: The expression level of l-CaD was significantly increased in primary colon cancer and liver metastasis tissues compared to the level in the corresponding normal tissues. In cancerous tissues obtained from the patients showing poor response to CRT (Dworak grade 4), the expression of l-CaD was increased compared to that of good response group (Dworak grade 1). In line with, l-CaD positive human colon cancer cell lines were more resistant to 5-fluorouracil (5-FU) and radiation treatment compared to l-CaD negative cell lines. Artificial suppression of l-CaD increased susceptibility of colon cancer cells to 5-FU, and caused an increase of p21 and c-PARP, and a decrease of NF-kB and p-mTOR expression. CONCLUSION: Up-regulated expression of l-CaD may have a role for increasing metastatic property and decreasing CRT susceptibility in colorectal cancer cells.
    BMC Cancer 12/2012; 12(1):601. · 3.33 Impact Factor

Publication Stats

573 Citations
192.55 Total Impact Points

Institutions

  • 2004–2014
    • National Cancer Center Korea
      • Colorectal Cancer Branch
      Kōyō, Gyeonggi Province, South Korea
  • 2013
    • National Cancer Institute (USA)
      Maryland, United States
  • 2012–2013
    • Sungkyunkwan University
      • Department of Genetic Engineering
      Seoul, Seoul, South Korea
  • 2010–2011
    • Kangwon National University
      • Department of Bioengineering and Technology
      Shunsen, Gangwon, South Korea
  • 2008
    • Seoul National University Hospital
      • Department of Surgery
      Seoul, Seoul, South Korea
  • 2004–2007
    • Seoul National University
      • Cancer Research Institute
      Seoul, Seoul, South Korea