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ABSTRACT: Sophoricoside (SOPH) is an isoflavone isolated from Sophora japonica (Leguminosae). In this study, the inhibitory effect of SOPH on contact dermatitis was investigated. At dosages of 3 and 10mg/kg, SOPH ameliorated 2,4-dinitrochlorobenzene-induced acute and chronic contact dermatitis by 50-70%. As cellular targets, SOPH mainly affected the functions of B cells rather than T cells, macrophages and dendritic cells. As signaling targets, SOPH inhibited the phosphorylation and degradation of IκBα/β and the nuclear translocation of NF-κB p65 in B cells, but not in dendritic cells and macrophages. SOPH did not affect the phosphorylation of ERK, p38, and JNK MAPKs, in B cells, dendritic cells, and macrophages. Taken together, these results suggest that SOPH ameliorates contact dermatitis by inhibiting mainly NF-κB signaling in B cells.
International immunopharmacology 02/2013; 15(3):467-473. · 2.21 Impact Factor
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Jung Hyu Shin,
Chang Woo Lee,
Soo Jin Oh,
Jieun Yun,
Kiho Lee,
Song-Kyu Park,
Hwan Mook Kim,
Sang-Bae Han,
Youngsoo Kim,
Hyung Chin Kim, Jong Soon Kang
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ABSTRACT: Silymarin has been known to exert antioxidant, anti-carcinogenic and anti-inflammatory effects. In this study, we examined the effect of silymarin on gastritis in rats. Oral administration of silymarin dose-dependently decreased gastric lesions in ethanol-induced gastritis model. Silymarin also significantly suppressed the development of gastric lesions in aspirin- or water immersionrestraint stress-induced gastritis models. Further study demonstrated that the gastroprotective effect of silymarin was blocked by nitric oxide (NO) synthase inhibitor L-NAME, SH blocker Nethylmaleimide or TRPV1 antagonist capsazepine in ethanol-induced gastritis model. In addition, ex vivo analysis revealed that ethanol-induced decrease in gastric mucus and non-protein sulfhydryl (NPSH) groups was significantly reversed by silymarin treatment and lipid peroxidation was also suppressed by silymarin in ethanol-induced gastritis model. Taken together, these results suggest that silymarin exerts gastroprotective effects and the gastroprotective effects of silymarin might be related to the protection of gastric mucosal NO and NP-SH and the modulation of capsaicin-sensitive gastric sensory afferents.
Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 01/2013; · 2.99 Impact Factor
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ABSTRACT: To determine the effect of type-2 diabetes and obesity on the hepatic metabolism of sulfur amino acids, hepatic sulfur amino acid metabolism was determined in db/db mice. Hepatic methionine was markedly decreased in db/db mice, although the hepatic activity of betaine homocysteine methyltransferase was increased. The decrease in hepatic methionine was reflected by decreased sulfur-containing methionine metabolites, including S-adenosylmethionine, homocysteine, cysteine, and hypotaurine in liver and plasma. In contrast, S-adenosylhomocysteine, putrescine, and spermidine were increased in db/db mice. The hepatic level and activity of methionine adenosyltransferase I/III, an S-adenosylmethionine synthesizing enzyme, were significantly increased. These results suggest that increased polyamine synthesis, in conjunction with decreased hepatic methionine levels, is partly responsible for the reduction in hepatic S-adenosylmethionine. Decreased homocysteine in liver and plasma may be attributable to the decrease in hepatic methionine and upregulation of hepatic betaine homocysteine methyltransferase. Glutathione in liver and plasma did not change despite decreased -glutamylcysteine ligase activity. The decreased hepatic hypotaurine may be attributable to the downregulation of cysteine dioxygenase. The major finding of this study is that db/db mice exhibited decreases in hepatic methionine and its sulfurcontaining metabolites.
Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 12/2012; · 2.99 Impact Factor
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ABSTRACT: Kamebakaurin (KA) has anti-cancer and anti-inflammatory activities through direct inhibition of DNA-binding activity of nuclear factor-kappa B (NF-κB) p50. We suggest here another molecular target of KA by the use of lipopolysaccharide-treated dendritic cells. In cell- and enzyme-based assays, KA directly inhibited autophosphorylation and kinase activity of TAK1, followed by the inhibition of TAK1-downstream signaling cascades, such as IKK phosphorylation-IκBα degradation-nuclear translocation of NF-κB, phosphorylation of MEK3/6-p38 mitogen activated protein kinase (MAPK), and MKK4/7-c-Jun N-terminal kinase MAPK. These results demonstrated that TAK1 might be the direct molecular target of KA.
International immunopharmacology 11/2012; · 2.21 Impact Factor
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ABSTRACT: Effusanin C, a constituent of Isodon japonicus, has been used in oriental countries as a traditional folk medicine to treat inflammatory diseases, but its mechanism of action remains unknown. Here, we investigate the inhibitory activity of effusanin C in inflammatory monocytes. Effusanin C markedly inhibited the production of inflammatory mediators including nitric oxide, IL-1β, and TNF-α in macrophages and dendritic cells. Furthermore, molecular studies showed that effusanin C inhibited phosphorylation of p38, JNK, and ERK, degradation of IκBβ, and nuclear translocation of NF-κB p50/p65 in these cells. Taken together, these data show that effusanin C inhibits inflammatory responses by blocking NF-κB and MAPK signalings in monocytes.
International immunopharmacology 11/2012; · 2.21 Impact Factor
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ABSTRACT: Artemisinin is a well-known anti-malarial drug and has been shown to inhibit nitric oxide (NO) production. In this study, we investigated the effect of artemisinin on lipopolysaccharide (LPS)-induced production of IFN-β and characterized the potential relationship between artemisinin-mediated inhibition of IFN-β and NO production. Artemisinin suppressed IFN-β production and mRNA expression in a dose-dependent manner in LPS-stimulated RAW 264.7 cells. LPS-induced phosphorylation of signal transducer and activator of transcription-1 (STAT-1) was also inhibited by artemisinin treatment in RAW 264.7 cells. In addition, artemisinin suppressed LPS-induced production of NO in RAW 264.7 cells. Further study demonstrated that artemisinin-mediated inhibition of NO production and STAT-1 phosphorylation was reversed by addition of exogenous IFN-β. Moreover, artemisinin does not affect IFN-β-induced STAT-1 phosphorylation in RAW 264.7 cells. Collectively, these results suggest that the inhibition of IFN-β production by artemisinin and concomitant attenuation of STAT-1 activation might be involved in artemisinin-mediated inhibition of NO production in macrophages.
International immunopharmacology 10/2012; 14(4):580-584. · 2.21 Impact Factor
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ABSTRACT: Paecilomyces cicadae have been reported to have immunomodulatory properties. In this study, we investigated the effect of polysaccharide (PCP) isolated from P. cicadae on the macrophages. PCP increased the production of nitric oxide (NO) and the gene expression of IL-1β, IL-6, and TNF-α in RAW 264.7 cells. To investigate the membrane receptor, we examined the effect of PCP on primary macrophages isolated from wild type C3H/HeN and C3H/HeJ mice having mutant-TLR4. PCP induced NO production and cytokine gene expression in macrophages from C3H/HeN, but not from tlr4-mutated C3H/HeJ mice, which suggests that TLR4 is the membrane receptor for PCP. PCP induced the phosphorylation of ERK, JNK, and p38, and the nuclear translocation of NF-κB p50/p65, which are the main signaling molecules downstream from TLR4. Among them, p38 and NF-κB signaling played a crucial role in PCP-induced NO production by macrophages. These results indicate that PCP activates macrophages through the TLR4 signaling pathway.
Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 06/2012; 50(9):3190-7. · 2.99 Impact Factor
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Moo Rim Kang,
Song-Kyu Park,
Chang Woo Lee,
Ig Jun Cho,
Yeong Nang Jo,
Jeong Wook Yang,
Jin-Ah Kim,
Jieun Yun,
Ki Hoon Lee,
Hyun Ju Kwon,
Byung Woo Kim,
Kiho Lee, Jong Soon Kang,
Hwan Mook Kim
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ABSTRACT: Widdrol, a natural sesquiterpene present in Juniperus sp., has been shown to exert anticancer and antifungal effects. Emerging evidence has suggested that AMP-activated protein kinase (AMPK), which functions as a cellular energy sensor, is a potential therapeutic target for human cancers. In this study, we found that AMPK mediates the anticancer effects of widdrol through induction of apoptosis in HT-29 colon cancer cells. We showed that widdrol induced the phosphorylation of AMPK in a dose- and time-dependent manner. The selective AMPK inhibitor compound C abrogated the inhibitory effect of widdrol on HT-29 cell growth. In addition, we demonstrated that widdrol induced apoptosis and this was associated with the activation of caspases, including caspase‑3/7 and caspase-9, in HT-29 cells. We also demonstrated that transfection of HT-29 cells with AMPK siRNAs significantly suppressed the widdrol-mediated apoptosis and the activation of caspases. However, cell cycle arrest induced by widdrol was not affected by transfection of HT-29 cells with AMPK siRNAs. Furthermore, widdrol inhibited HT-29 tumor growth in a human tumor xenograft model. Taken together, our results suggest that the anticancer effect of widdrol may be mediated, at least in part, by induction of apoptosis via AMPK activation.
Oncology Reports 05/2012; 27(5):1407-12. · 1.84 Impact Factor
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ABSTRACT: BAFF is associated with various immunological diseases. Previously, we have reported that mouse B cell activating factor (mBAFF) expression was dependent on nuclear localization of co-activator, p300 and the activation of transcription factors including NF-κB and CREB. Here, we investigated whether transcription factor, c-Fos, regulates human (h) BAFF expression through promoter activation by PMA-induced reactive oxygen species (ROS) production. We cloned hBAFF promoter into luciferase-expressing pGL3-basic vector. The activity of 1.0 kb hBAFF promoter was higher than that in 0.75, 0.5 or 0.25 kb hBAFF promoter. The existence of three AP-1 binding motifs was computer-analyzed in hBAFF promoter. The stimulation with PMA and ionomycin (IOM) increased 1.0 kb hBAFF promoter activity, time-dependently. PMA/IOM-stimulation rapidly enhanced c-Fos expression in THP-1 human pro-monocytic cells. Binding of c-Fos to hBAFF promoter was detected by chromatin immunoprecipitation (ChIP) assay. hBAFF expression and its promoter activity were decreased by the transfection with small interference (si) RNA of c-Fos. ROS production in THP-1 cells was increased by PMA/IOM-stimulation. In addition, hBAFF activity stimulated by PMA/IOM was reduced by N-acetyl-cysteine (NAC), a well-known ROS scavenger. Serum starvation (0.5% FBS) producing ROS and the exogenous H(2)O(2) treatment also enhanced hBAFF promoter activity. c-Fos expression and AP-1 binding to oligonucleotide were reduced by the treatment with NAC. H(2)O(2) was not able to induce hBAFF expression in the presence of staurosporine, PKC inhibitor. Data suggest that hBAFF expression could be regulated by promoter activation through c-Fos association, which might be dependent on PMA-induced ROS production.
Cytokine 04/2012; 59(1):115-23. · 3.02 Impact Factor
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ABSTRACT: To evaluate the reliability and accuracy of the apparent diffusion coefficient (ADC) for monitoring antiangiogenic treatment in a longitudinal study.
Tumor volume and ADC were monitored by T2-weighted magnetic resonance imaging (MRI) and diffusion-weighted MRI, respectively, in 18 mice with angiogenesis-dependent tumors (U118MG) before (day 0) and after 2, 7, 14, and 21 days of administration of the antiangiogenic agent sunitinib maleate (n = 12) or vehicle (n = 6). Percent changes in tumor volume and ADC were calculated and correlations between tumor volume and ADC were evaluated.
Tumor volume and ADC showed a negative correlation at 69 of the 72 (96%) follow-up measurements. In the 13 mice with tumor regrowth, ADC started to decrease before (27%) or at the same time (73%) as tumor regrowth. Pretreatment ADC and percent change in ADC change on days 0-2 were similar in mice with positive and negative responses to treatment (0.851 vs. 0.999, 24% vs. 16%). Percent change of ADC showed significant negative correlation with percent change in tumor volume in both the control (r = -0.69) and treated (r = -0.65) groups.
Percent change in ADC is a reliable and accurate marker for monitoring the effects of antiangiogenic treatment, whereas pretreatment ADC and early changes in ADC (ie, days 0-2) are limited in predicting treatment outcome.
Journal of Magnetic Resonance Imaging 02/2012; 35(6):1430-6. · 2.70 Impact Factor
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Moo Rim Kang, Jong Soon Kang,
Jeong Wook Yang,
Bo Geun Kim,
Jin-Ah Kim,
Yeong Nang Jo,
Kiho Lee,
Chang Woo Lee,
Ki Hoon Lee,
Jieun Yun,
Hwan Mook Kim,
Gyoonhee Han,
Jong Seong Kang,
Song-Kyu Park
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ABSTRACT: The aim of this study was to investigate the anti-tumor activity of KBH-A42, a novel synthetic histone deacetylase (HDAC) inhibitor. KBH-A42 was shown to significantly suppress the proliferation of all 14 human cancer cell lines tested. Among these cell lines, the human leukemia cell line K562 was the most sensitive, whereas the UM-UC-3 bladder cancer cells were the least sensitive. Additionally, in a human tumor xenograft model using Balb/c nude mice, KBH-A42 was shown to significantly inhibit the growth of K562 tumors, although it only slightly inhibited the growth of UM-UC-3 tumors. The results of flow cytometry analysis and caspase 3/7 activation assays showed that the growth inhibition of K562 cells by KBH-A42 was mediated, at least in part, by the induction of apoptosis, but its growth inhibitory effects on UM-UC-3 cells were not mediated by apoptotic induction. In an effort to gain insight into the mechanism by which KBH-A42 inhibits the growth of cancer cells, a microarray analysis was conducted. Four genes were selected from the genes that were down-regulated or up-regulated by KBH-A42 and confirmed via reverse transcription-polymerase chain reaction as follows: Harakiri (HRK), tumor necrosis factor receptor superfamily, member 10b (TNFRSF10B), PYD and CARD domain containing protein gene (PYCARD) and tumor necrosis factor receptor superfamily, member 8 (TNFRSF8). Collectively, the in vitro and in vivo results suggested that KBH-A42 exhibits anti-cancer activity, but various types of cells may be regulated differentially by KBH-A42.
Oncology letters 01/2012; 3(1):113-118. · 0.11 Impact Factor
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ABSTRACT: The clinical efficacy of dendritic cell (DC) vaccine in cancer patients has been unsatisfactory due, at least in part, to the deficiency of maturation and impaired migration of ex vivo generated DCs to the draining lymph nodes. To solve this problem, we used angelan, a natural TLR4 ligand, to enhance the maturation and migration of DCs. Angelan increased the expression of MHC-I/II, CD80, and CD86, DC maturation markers, through the NF-κB pathway. This compound also increased CCR7 expression in DCs through NF-κB and p38 pathway and enhanced their migration against CCL19, which is a key chemokine that guides DCs into lymph nodes. We also showed that angelan enhanced in vivo DC homing from tissues to draining lymph nodes. When treated to DCs in vitro and vivo, angelan increased antitumor activity of DCs in B16F10 syngeneic tumor model. Taken together, the present data suggest that a natural TLR4 ligand might be helpful for overcoming the disadvantages of DC-based cancer therapy, such as impaired maturation and poor migration in cancer patients.
Cancer letters 12/2011; 313(2):226-34. · 4.86 Impact Factor
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Hyo-Jung Kwon,
Young-Suk Won,
Ki-Taek Nam,
Yeo-Dae Yoon,
Hyang Jee,
Won-Kee Yoon,
Ki-Hoan Nam, Jong-Soon Kang,
Sang-Uk Han,
In-Pyo Choi,
Dae-Yong Kim,
Hyoung-Chin Kim
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ABSTRACT: Vitamin D(3) upregulated protein 1 (VDUP1) is a potent tumour suppressor whose expression is dramatically reduced in various types of human cancers, including gastric cancer. However, the precise mechanisms underlying tumour development remain unclear. In the present study, the authors examined the effect of VDUP1 on Helicobacter pylori-induced gastric carcinogenesis in mice.
Gastric cancer was generated in VDUP1 knockout (KO) and wild-type mice using a combination of N-methyl-N-nitrosourea treatment and H pylori infection. Fifty weeks after treatment, gastric tissues from both types of mice were examined by histopathology, immunohistochemistry and immunoblotting. In vitro tests on the human gastric cancer cell line, AGS, were also performed to identify the underlying mechanisms of cancer development.
The overall incidence of gastric cancer was significantly higher in VDUP1 KO mice than in wild-type mice. Similarly, VDUP1 KO mice showed more severe chronic gastritis, glandular atrophy, foveolar hyperplasia, metaplasia and dysplasia. Although no differences in the apoptotic index were apparent, lack of VDUP1 increased the rate of gastric epithelial cell proliferation in non-cancerous stomachs, with corresponding increases in tumour necrosis factor alpha (TNFα) level, nuclear transcription factor kappa B (NF-κB) activation and cyclooxygenase-2 (COX-2) expression. An in vitro study showed that H pylori-associated cell proliferation and induction of TNFα, NF-κB and COX-2 were inhibited in cells transfected with VDUP1. In addition, overexpression of VDUP1 in AGS cells suppressed TNFα-induced NF-κB activation and COX-2 expression.
Our data show that VDUP1 negatively regulates H pylori-associated gastric carcinogenesis, in part by disrupting cell growth and inhibiting the induction of TNFα, NF-κB and COX-2. These findings provide important insights into the role of VDUP1 in H pylori-associated tumourigenesis.
Gut 09/2011; 61(1):53-63. · 10.11 Impact Factor
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Jong Soon Kang,
Won Kyung Lee,
Chang Woo Lee,
Won Kee Yoon,
Nayang Kim,
Sang-Ki Park,
Heon-Sik Lee,
Hyoung Kook Park,
Sang-Bae Han,
Jieun Yun,
Kiho Lee,
Ki Hoon Lee,
Song-Kyu Park,
Hwan Mook Kim
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ABSTRACT: In the present study, we examined the effect of a mixture of dietary components, including red grape extract, soy isoflavone and L-carnitine (RISC), on obesity. RISC substantially inhibited high-fat diet (HFD)-induced increase in body weight in a dose-dependent manner in C57BL/6 mice. The amount of subcutaneous and mesenteric fat was also significantly decreased by RISC treatment in HFD-fed C57BL/6 mice, whereas epididymal fat was not affected. Moreover, HFD-induced plasma leptin levels were down-regulated by RISC treatment. In these mice, RISC treatment significantly increased the plasma level of high density lipoprotein cholesterol without affecting the level of low density lipoprotein cholesterol and triglycerides. In addition, HFD-induced increase in liver weight and lipid accumulation in liver was significantly suppressed by RISC treatment in C57BL/6mice. Plasma level of glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase was also inhibited by RISC treatment. These results demonstrate that RISC suppresses HFD-induced obesity and suggest that RISC supplementation might be a promising adjuvant therapy for the treatment of obesity and its complications, such as cardiovascular and non-alcoholic fatty liver diseases.
Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 09/2011; 49(9):2453-8. · 2.99 Impact Factor
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ABSTRACT: Paecilomyces cicadae Miquel Samson is the anamorph of Cordyceps cicadae Shing and is used in functional foods for the prevention and treatment of various diseases. In the present study, we examined the effects of P. cicadae polysaccharide (PCP) on dendritic cell (DC) maturation. Phenotypic maturation of DCs by PCP was confirmed by the elevated expressions of CD80, CD86, major histocompatibility complex (MHC)-I, and MHC-II molecules and functional maturation by increased expression of interleukin-12, interleukin-1β, and tumor necrosis factor-α, enhanced allogenic T cell stimulation, and decreased endocytosis. PCP induced the maturation of DCs from C3H/HeN and C57BL/6 mice but not from Toll-like receptor (tlr) 4⁻/⁻ knockout mice and TLR4-mutated C3H/HeJ mice, which suggests that TLR4 is the membrane receptor for PCP. PCP increased the degradation of inhibitor of nuclear factor-κB (NF-κB) α/β, which enhanced the nuclear translocation of NF-κB p50/p65 and induced the phosphorylation of extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinases, which are signaling molecules downstream of TLR4. These results indicate that PCP induces DC maturation through TLR4 signaling.
Journal of medicinal food 06/2011; 14(7-8):847-56. · 1.39 Impact Factor
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ABSTRACT: This study was performed to elucidate the anticancer mechanism of a lipid-soluble ginseng extract (LSGE) by analyzing induction of apoptosis and arrest of cell cycle progression using the NCI-H460 human lung cancer cell line. Proliferation of NCI-H460 cells was potently inhibited by LSGE in a dose-dependent manner. The cell cycle arrest at the G0/G1 phase in NCI-H460 cells was induced by LSGE. The percentage of G0/G1 phase cells significantly increased, while that of S phase cells decreased after treatment with LSGE. The expression levels of cyclin-dependent kinase2 (CDK2), CDK4, CDK6, cyclin D3 and cyclin E related to G0/G1 cells progression were also altered by LSGE. In addition, LSGE-induced cell death occurred through apoptosis, which was accompanied by increasing the activity of caspases including caspase-8, caspase-9 and caspase-3. Consistent with enhancement of caspase activity, LSGE increased protein levels of cleaved caspase-3, caspase-8, caspase-9, and poly-ADP-ribose polymerase (PARP). These apoptotic effects of LSGE were inhibited by the pan-caspase inhibitor Z-VAD-fmk. These findings indicate that LSGE inhibits NCI-H460 human lung cancer cell growth by cell cycle arrest at the G0/G1 phase and induction of caspase-mediated apoptosis.
Materiae Vegetabiles 05/2011; 66(2):101-6. · 2.51 Impact Factor
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Seung Jin Lee,
Hye Young Kang,
Seog Young Kim,
Jin Hwa Chung,
Seung Jun Oh,
Jin-Sook Ryu,
Sung-Bae Kim, Jong Soon Kang,
Song-Kyu Park,
Hwan Mook Kim,
Myung-Hwa Kim,
Dae Hyuk Moon
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ABSTRACT: We determined whether [(18)F]fluorothymidine (FLT) positron emission tomography (PET) can detect early effects on tumor proliferation of JAC106, a new anti-tubulin agent.
Inhibition of tubulin polymerization and [(3)H]colchicine binding were assessed in vitro. The effects of JAC106 on cytotoxicity, mitotic arrest, [(18)F]FLT uptake, and thymidine kinase 1 (TK1) activity were examined in SW620 and KB-V1 cells. Dose-dependent antitumor effects of JAC106 were monitored by measuring tumor growth and by dynamic [(18)F]FLT PET imaging in mice bearing SW620 and KB-V1 tumors. The proliferation status of tumors was examined.
JAC106 potently inhibited tubulin polymerization and decreased the viability of SW620 (p < 0.001, half maximal inhibitory concentration, IC(50) = 3.15 ± 1.4) and KB-V1 (p < 0.01, IC(50) = 21.84 ± 24.59) cells. Exposure to JAC106 induced mitotic arrest starting at 18 h and dose-dependently increased [(18)F]FLT uptake/1 × 10(5) cells (p < 0.05) and TK1 activity and expression in vitro. Administration of 30 mg/kg JAC106 to mice inhibited the growth of SW620 and KB-VI tumors (%T/C 3.34 and 20.6%, respectively). The baseline standardized uptake values (SUV) of SW620 and KB-V1 tumors were 0.96 ± 0.31 and 2.29 ± 0.70, respectively, with a significant difference (p < 0.01). After 3 days of treatment with 30 mg/kg JAC106, the [(18)F]FLT SUVs of SW620 and KB-V1 tumors, normalized to those before treatment, were 77.9 ± 22.4% (p = 0.059) and 43.2 ± 14.0% (p < 0.01), respectively. JAC106 significantly decreased the number of Ki-67-positive cells, TK1 activity, cell fraction in G(0)G(1) phase, and tumor expression of cyclins E, A, and B1 on day 3.
[(18)F]FLT PET can be used to monitor JAC106 inhibition of tumor growth, beginning 3 days after treatment. Incorporation of [(18)F]FLT PET may be useful in the early clinical development of JAC106.
European Journal of Nuclear Medicine 04/2011; 38(8):1436-48. · 4.53 Impact Factor
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Jong Soon Kang,
Won Kyung Lee,
Won Kee Yoon,
Nayang Kim,
Sang-Ki Park,
Hyoung Kook Park,
Sun Yung Ly,
Sang-Bae Han,
Jieun Yun,
Chang Woo Lee,
Kiho Lee,
Ki Hoon Lee,
Song-Kyu Park,
Hwan Mook Kim
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ABSTRACT: To develop a therapeutic agent for obesity-related metabolic disorders, a mixture of dietary components was prepared, including grape extract, green tea extract and l-carnitine (RGTC), and its effects on obesity, hyperlipidemia and non-alcoholic fatty liver disease examined. The RGTC dramatically inhibited the high-fat diet (HFD)-induced increase in body weight and fat in C57BL/6 mice, whereas food consumption was not affected by RGTC treatment. The RGTC also concentration-dependently suppressed the HFD-induced increase in plasma lipids, such as low-density lipoprotein cholesterol and triglycerides. In addition, increases in liver weight and liver steatosis were returned to normal by RGTC treatment in HFD-fed C57BL/6 mice. The plasma levels of glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase were also significantly down-regulated by RGTC treatment. These results suggest that RGTC suppressed HFD-induced obesity, hyperlipidemia and non-alcoholic fatty liver disease, suggesting that RGTC supplementation might be a promising adjuvant therapy for the treatment of these metabolic disorders.
Phytotherapy Research 04/2011; 25(12):1789-95. · 2.09 Impact Factor
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ABSTRACT: Histone deacetylases (HDACs) are involved in post-translational modification and gene expression. Cancer cells recruited amounts of HDACs for their survival by epi-genetic down regulation of tumor suppressor genes. HDACs have been the promising targets for treatment of cancer, and many HDAC inhibitors have been investigated nowadays. In previous study, we synthesized δ-lactam core HDAC inhibitors which showed potent HDAC inhibitory activities as well as cancer cell growth inhibitory activities. Through QSAR study of the δ-lactam based inhibitors, the smaller core is suggested as more active than larger one because it fits better in narrow hydrophobic tunnel of the active pocket of HDAC enzyme. The smaller γ-lactam core HDAC inhibitors were designed and synthesized for biological and property optimization. Phenyl, naphthyl and thiophenyl groups were introduced as the cap groups. Hydrophobic and bulky cap groups increase potency of HDAC inhibition because of hydrophobic interaction between HDAC and inhibitors. In overall, γ-lactam based HDAC inhibitors showed more potent than δ-lactam analogues.
Bioorganic & medicinal chemistry letters 02/2011; 21(4):1218-21. · 2.65 Impact Factor
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Hyung Sook Kim,
Jee Youn Kim,
Hong Kyung Lee,
Moo Sung Kim,
Sang Rin Lee, Jong Soon Kang,
Hwan Mook Kim,
Kyung-Ae Lee,
Jin Tae Hong,
Youngsoo Kim,
Sang-Bae Han
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ABSTRACT: Lichen-derived glucans have been known to stimulate the functions of immune cells. However, immunostimulatory activity of glucan obtained from edible lichen, Umbilicaria esculenta, has not been reported. Thus we evaluated the phenotype and functional maturation of dendritic cells (DCs) following treatment of extracted glucan (PUE).
The phenotypic and functional maturation of PUE-treated DCs was assessed by flow cytometric analysis and cytokine production, respectively. PUE-treated DCs was also used for mixed leukocyte reaction to evaluate T cell-priming capacity. Finally we detected the activation of MAPK and NF-κB by immunoblot.
Phenotypic maturation of DCs was shown by the elevated expressions of CD40, CD80, CD86, and MHC class I/II molecules. Functional activation of DCs was proved by increased cytokine production of IL-12, IL-1β, TNF-α, and IFN-α/β, decreased endocytosis, and enhanced proliferation of allogenic T cells. Polymyxin B, specific inhibitor of lipopolysaccharide (LPS), did not affect PUE activity, which suggested that PUE was free of LPS contamination. As a mechanism of action, PUE increased phosphorylation of ERK, JNK, and p38 MAPKs, and enhanced nuclear translocation of NF-κB p50/p65 in DCs.
These results indicate that PUE induced DC maturation via MAPK and NF-κB signaling pathways.
Immune Network 12/2010; 10(6):188-97.
