• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6791-6798
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• 2014

Background: To investigate the effect of silibinin on proliferation and apoptosis in human gastric cancer cell line MGC803 and its possible mechanisms. Materials and Methods: Human gastric cancer cell line MGC803 cells were treated with various concentration of silibinin. Cellular viability was assessed by CCK-8 assay andapoptosis and cell cycle distribution by flow cytometry. Protein expression and mRNA of STAT3, and cell cycle and apoptosis regulated genes were detected by Western blotting and real-time polymerase chain reaction, respectively. Results: Silibinin inhibits growth of MGC803 cells in a dose- and time-dependent manner. Silibinin effectively induces apoptosis of MGC803 cells and arrests MGC803 cells in the G2/M phase of the cell cycle, while decreasing the protein expression of p-STAT3, and of STAT3 downstream target genes including Mcl-1, Bcl-xL, survivin at both protein and mRNA levels. In addition, silibinin caused an increase in caspase 3 and caspase 9 protein as well as mRNA levels. Silibinin caused G2/M phage arrest accompanied by a decrease in CDK1 and Cyclin B1 at protein and mRNA levels.. Conclusions: These results suggest that silibinin inhibits the proliferation of MGC803 cells, and it induces apoptosis and causes cell cycle arrest by down-regulating CDK1, cyclinB1, survivin, Bcl-xl, Mcl-1 and activating caspase 3 and caspase 9, potentially via the STAT3 pathway.

• Bulletin of the Korean Chemical Society
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• v.15 no.6
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• pp.432-436
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• 1994

Monomeric rhodium and iridium-diaryltetrazene complexes $Cp^*$M(RNN=NNR)($Cp^*$=1,2,3,4,5-pentamethylcyclope ntadienyl; M=Rh, Ir; R=Ph, 4-tolyl) have been synthesized from [$Cp^*MCl_2]_2$(M=Rh, Ir) and 2 equiv. of $[Li(THF)_x]_2(RN_4$R) in benzene. We have determined the crystal structure of (${\eta}^5$-pentamethylcyclopentadienyl)diphenyltetrazene iridium by using graphite-monochromated Mo-$K_a$ radiation. The compound was crystallized in the monoclinic space group $P2_{1/c}$ with a=13.781(3), b=9.035(l), c=17.699(3) ${\AA}$, and ${\beta}=111.93(l)^{\circ}$. An X-ray crystal structure of complex 1 showed a short N(2)-N(3) distance ($1.265 {\AA}$) consistent with the valence tautomer A with Ir(III) rather than Ir(I). All complexes are highly colored and decompose on irradiation at 254 nm. Electrochemical studies show that complex 1 displays a quasi-reversible reduction.

• Advances in Traditional Medicine
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• v.10 no.4
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• pp.254-262
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• 2010

Artemisia capillaris (A. capillaries) is known to play roles in many cellular events, such as cell proliferation, differentiation, and apoptosis. We investigated the antifibrogenic efficacy of A. capillaris in the immortalized human hepatic stellate cell line LX2. Cell proliferation was determined by the MTT assay. Cell cycle was analyzed by the flow cytometry. Apoptotic cells were measured using a cell death detection ELISA. Caspase activity was detected by a colorimetric assay. The mRNA level of Bcl-2 and Bax mRNA were measured by real-time PCR. MEK and ERK protein were detected by Western blot analysis. We provide evidence that A. capillaris induces cell cycle arrest, apoptosis, and potently inhibits the mitogen-activated protein kinase pathway. A. capillaris inhibited cell proliferation of LX2 cells in a dose- and time-dependent manner, increased the apoptosis fraction at cell cycle analysis with an accompanying DNA fragmentation, and resulted in a significant decrease in Bcl-2 mRNA levels and an increase in Bax expression. Exposure of LX2 cells to A. capillaris induced caspase-3 activation, but co-treatment of A. capillaris with the pan-caspase inhibitor Z-VAD-FMK, and the caspase-3 inhibitor Z-DEVE-FMK, blocked apoptosis. A. capillaris down-regulated Mcl-1 protein levels and inhibited phosphorylation of MEK/ERK, suggesting that it mediates cell death in LX2 cells through the down-regulation of Mcl-1 protein via a MEK/ERK-independent pathway.

• Biomolecules & Therapeutics
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• v.14 no.2
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• pp.90-95
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• 2006

CKD-602 exerts its antitumor effect via inhibition of topoisomerase I in cancer cells. Multicellular spheroid (MCS) and Multicellular layers (MCLs) are known as in vitro 3-dimensional models which closely represent tumor conditions in vivo. In order to investigate the potential of CKD-602 against human colorectal tumors, we evaluated the anti-proliferative activity and penetration ability of CKD-602 in MCS and MCL cultures of DLD-l human colorectal cancer cells, respectively. The maximum effects($E_{max}$) induced by CKD-602 were significantly lower in MCS compared to monolayers (48% vs 92%). With prolonged drug exposure, the $IC_{50's}$ of CKD-602 decreased to $23.5{\pm}1.0nM$ in monolayers after 24 h exposure and $42.3{\pm}1.7nM$ in MCS after 6 days, respectively. However, no further increase in effect was observed for exposure time longer than growth doubling time (Td) in both cultures. Activity of CKD-602 was significantly reduced after penetration through MCL and also with cell-free insert membrane. In conclusion, CKD-602 showed significantly decreased anti-proliferative activity in 3D cultures (MCS) of human colorectal cancer cells. Tumor penetration of CKD-602 could not be determined due to loss of activity after penetration through cell free insert membrane, which warrants further evaluation using a modified model.

• Journal of Life Science
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• v.22 no.10
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• pp.1277-1285
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• 2012

The tumor necrosis, factor-related, apoptosis-inducing ligand (TRAIL) is regarded as a potentially useful anticancer agent with excellent selectivity for cancer cells. However, a considerable number of cancer cells are resistant to apoptosis induction by TRAIL. Developing strategies to overcome this resistance are important for the successful use of TRAIL for cancer therapy. Here, we revealed that siRNA-mediated downregulation of SIRT1 or SIRT1 inhibitor Amurensin G upregulated DR5 and c-Myc and downregulated c-$FLIP_{L/S}$ and Mcl-1, which was associated with sensitization of TRAIL-resistant MCF-7 cells to TRAIL. This result was followed by the activation of caspases, PARP cleavage, and downregulation of Bcl-2 in both TRAIL-treated MCF-7 cells transfected with SIRT1 siRNA and cells co-treated with Amurensin G and TRAIL. Our results suggest that the induction of DR5 and downregulation of c-FLIP via suppression of SIRT1 expression may be a useful strategy to increase the susceptibility of TRAIL-resistant cancer cells to TRAIL-induced cell death.

• Journal of Soil and Groundwater Environment
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• v.16 no.6
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• pp.133-142
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• 2011

A total of 247 samples were collected from groundwater being used for drinking-water supply, and hydrogeochemistry and radionuclide analysis were performed. In-situ analysis of groundwaters resulted in ranges of $13.7{\sim}25.1^{\circ}C$ for temperature, 5.9~8.5 for pH, 33~591 mV for Eh, $66{\sim}820{\mu}S/cm$ for EC, and 0.2~9.4 mg/L for DO. Major cation and anion concentrations of groundwaters were in ranges of 0.5~227.6 for Na, 1.0~279.3 for Ca, 0.0~9.3 for K, 0.1~100.1 for Mg, 0.0~3.3 for F, 0.9~779.1 for Cl, 0.3~120.4 for $SO_4$, 0.0~27.4 for $NO_3$-N, and 6~372 mg/L for $HCO_3$. Uranium-238 and radon-222 concentrations were detected in ranges of N.D-$131.1{\mu}g/L$ and 18-15,953 pCi/L, respectively. In case of some groundwaters exceeding USEPA MCL level ($30{\mu}g/L$) for uranium concentration, their pH ranged from 6.8 to 8.0 and Eh showed a relatively low value(86~199 mV) compared to other areas. Most groundwaters belonged to Ca-(Na)-$HCO_3$ type, and groundwaters of metamorphic rock exhibited the highest concentration of Na, Mg, Ca, Cl, $NO_3$-N, U, and those of plutonic rock showed the highest concentration of $HCO_3$, and Rn. Uranium and fluoride from granite areas did not show any correlation. However, uranium and bicarbonate displayed a positive relation of some areas in plutonic rocks($R^2$=0.3896).

• Journal of Environmental Science International
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• v.27 no.8
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• pp.651-663
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• 2018

The hydrochemistry of groundwater from 47 wells in the Chungwon area, Korea was analyzed to examine the occurrence of natural radionuclides like uranium and radon. The range of Electrical Conductivity (EC) value in the study area was $67{\sim}1,404{\mu}S/cm$. In addition to the high EC value, the content of cations and anions also tends to increase. Uranium concentrations ranged from $ND{\sim}178{\mu}g/L$ (median value, $0.8{\mu}g/L$) and radon concentrations ranged from 80~12,900 pCi/L (median value, 1,250 pCi/L). Uranium concentrations in one well, that is 2.8% of the samples, exceeded $30{\mu}g/L$, which is the Maximum Contaminant Level (MCL) proposed by the US Environmental Protection Agency (EPA), based on the chemical toxicity of uranium. Radon concentrations in three wells, that is 6% of the samples, and one well, that is 2.8% of the samples, exceeded 4,000 pCi/L (AMCL of the US EPA) and 8,100 pCi/L (Finland's guideline level), respectively. Concentrations of uranium and radon related to geology of the study area show the highest values in the groundwater of the granite area. The uranium and radon contents in the groundwater were found to be low compared to those of other countries with similar geological settings. It is likely that the measured value was lower than the actual content due to the inflow of shallow groundwater by the lack of casing and grouting.

• Journal of Microbiology and Biotechnology
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• v.15 no.6
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• pp.1330-1336
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• 2005

Polyhydroxyalkanoic acid (PHA) inclusion bodies were analyzed in situ by $^{13}C$-nuclear magnetic resonance ($^{13}C$-NMR) spectroscopy. The PHA inclusion bodies studied were composed of poly(3-hydroxybutyrate) or poly(3hydroxybutyrate-co-4-hydroxybutyrate), which was accumulated in Hydrogenophaga pseudoflava, and medium-chain-length PHA (MCL-PHA), which was accumulated in Pseudomonas fluorescens BM07 from octanoic acid or 11-phenoxyundecanoic acid (11-POU). The quantification of the $^{13}C$-NMR signals was conducted against a standard compound, sodium 2,2-dimethyl-2-silapentane-5-sulfonate (DSS). The chemical shift values for the in vivo NMR spectral peaks agreed well with those for the corresponding purified PHA polymers. The intracellular degradation of the PHA inclusions by intracellular PHA depolymerase(s) was monitored by in vivo NMR spectroscopy and analyzed in terms of first-order reaction kinetics. The H. pseudoflava cells were washed for the degradation experiment, transferred to a degradation medium without a carbon source, but containing 1.0 g/l ammonium sulfate, and cultivated at $35^{\circ}C$ for 72 h. The in vivo NMR spectra were obtained at $70^{\circ}C$ for the short-chain-length PHA cells whereas the spectra for the aliphatic and aromatic MCL-PHA cells were obtained at $50^{\circ}C\;and\;80^{\circ}C$, respectively. For the H. pseudoflava cells, the in vivo NMR kinetics analysis of the PHA degradation resulted in a first-order degradation rate constant of 0.075/h ($r^{2}$=0.94) for the initial 24 h of degradation, which was close to the 0.050/h determined when using a gas chromatographic analysis of chloroform extracts of sulfuric acid/methanol reaction mixtures of dried whole cells. Accordingly, it is suggested that in vivo $^{13}C$-NMR spectroscopy is an important tool for studying intracellular PHA degradation in terms of kinetics.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.11
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• pp.1599-1606
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• 2015

The purpose of this study was to assess the quality characteristics of Moju made with Hovenia dulcis Thunb. and its physiological effects on ICR mice. According to the sensory score, we selected Moju made with 1% Hovenia dulcis Thunb. among Moju made with 0, 0.5, 1, 5, and 10% Hovenia dulcis Thunb. Compared to Moju made without Hovenia dulcis Thunb., Moju made with 1% Hovenia dulcis Thunb. had higher proportions of moisture (86.77 g/100 g) and carbohydrates (11.86 g/100 g). The mean values of the physicochemical analyses were as follows: pH 4.91, acidity 0.28, $^{\circ}Brix$ 12.63, reducing sugar 68.97, alcohol content 0.1, alcohol density 0.998. Moju made with 1% Hovenia dulcis Thunb. did not have effects on DPPH radical scavenging activity; however, superoxide dismutase activity was significantly higher than that of Moju made without Hovenia dulcis Thunb. For assessing physiological activities, 4-week-old male ICR mice were divided into six groups (n=10): normal control group (NC), ethanol-administered group (EC), EC plus low-dose Moju made with 0% Hovenia dulcis Thunb. (MCL), EC plus high-dose Moju made with 0% Hovenia dulcis Thunb. (MCH), EC plus low-dose Moju made with 1% Hovenia dulcis Thunb. (MDL), and EC plus high-dose Moju made with 1% Hovenia dulcis Thunb. (MDH). Serum triglyceride (TG) level was reduced by 11.17% and 19.61% in the MDL and MDH groups, respectively, compared to the EC group. Serum total-cholesterol levels of MDL and MDH groups were significantly lower as compared to the EC group. Serum high-density lipoprotein-cholesterol levels of the MDL and MDH groups were significantly higher than those of the EC group. Liver TG levels were significantly reduced in the MCL and MDL groups. From these results, Moju made with Hovenia dulcis Thunb. demonstrated antioxidant activity and reduction of hyperlipidemia markers. Therefore, Moju made with Hovenia dulcis Thunb. can serve as a non-alcoholic beverage and functional food source.

• The Journal of Engineering Geology
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• v.23 no.4
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• pp.477-491
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• 2013

Natural radionuclides in groundwater in the Danyang area were investigated to characterize the behaviors of uranium and radon with respect to lithology and physico-chemical components, which can aid our understanding of their occurrence, properties, and origins. To this end, a total of 100 groundwater samples were collected and analyzed, and radionuclide levels were used to construct detailed concentration maps. The water type of the groundwater, assessed using a Piper diagram, is mainly Ca-Na-$HCO_3$. The concentrations of uranium range from 0.02 to $251.0{\mu}g/L$ (average, $3.85{\mu}g/L$) and only 1% exceed USEPA's MCL (Maximum Contaminant Level). Uranium is enriched in groundwaters of Cretaceous granites and Precambrian metamorphic rocks, whereas it is depleted in groundwaters of sedimentary rocks. The concentrations of radon range from 13 to 28,470 pCi/L (average, 2397 pCi/L). Only 15% of the samples exceed AMCL (Alternative Maximum Contaminant Level) of 4000 pCi/L. The radon concentration is highest in groundwater of Cretaceous granites and lowest in groundwater of sedimentary rocks. In conclusion, the distribution and occurrence of radionuclides are intimately related to the basic geological characteristics of the rocks in which the radiogenic minerals are primarily contained. The behavior of uranium is only weakly related to that of radon (correlation coefficient = 0.15). There are also weak correlations between radionuclides and the main chemical components, pH, EC, Eh, and well depth. Of note, the correlation coefficient between radon and $SiO_2$ is 0.68, and that between radon and $HCO_3$ is -0.48. Factor analysis shows that radionuclides behave somewhat independently of each other because there are no significant factors that control the behavior of chemical components as well as radionuclides. The detailed concentration maps during this study will be used to establish useful database of radionuclide distribution and geological properties throughout Korea.