• BMB Reports
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• v.42 no.12
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• pp.806-811
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• 2009

Recently, various phenolic acid phenethyl ureas (PAPUs) have been synthesized from phenolic acids by Curtius rearrangement for the development of more effective anti-oxidants. In this study, we examined the anti-tumor activity and cellular mechanism of the synthetic compound (E)-1-(3,4-dihydroxyphenethyl)-3-styrylurea (PAPU1) using melanoma B16/F10 and M-3 cells. Results showed that PAPU1 inhibited the cell proliferation and viability, but did not induce cytotoxic effects on primary cultured fibroblasts. PAPU1 induced apoptotic cell death rather than necrosis in melanoma cells, a result clearly proven by the shift of cells into sub-$G_1$ phase of the cell cycle and by the substantial increase in cells positively stained with TUNEL or Annexin V. Collectively, this study revealed that PAPU1 induced apoptosis in a caspase-dependent manner, suggesting a potential role as a cancer chemopreventive agent for melanoma cells.

• Natural Product Sciences
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• v.10 no.3
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• pp.129-133
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• 2004

Quercetin is a dietary anticancer chemical that is capable of inducing apoptosis in tumor cells. However, little is known about its biological effect in nonmalignant hepatic cells. Using embryonic normal hepatic cell line (BNL CL.2) and its SV40-transformed tumorigenic cell line (BNL SV A.8), we evaluated the effects of quercetin on cell proliferation and apoptosis. As the results, our present study demonstrated that quercetin had a selective growth inhibition in normal versus tumorigenic hepatic cells such that BNL SV A.8 cells were very sensitive to the quercetin-mediated cytotoxicity. In particular, as evidenced by the increased number of positively stained cells in the TUNEL assay, the induction of characteristic nuclear DNA ladders, and the migration of many cells to sub-G1 phase in the BNL SV A.8 cells, quercetin treatment more sensitively induced apoptosis in BNL SV A8 cells than in BNL CL.2 cells. Collectively, our findings suggest that quercetin can be approached as a potential agent that is capable of inducing selective growth inhibition and apoptosis of hepatic cancer cells.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2018.04a
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• pp.80-80
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• 2018

Chlorogenic acid is a phenolic compound found in Cudrania tricuspidata fruits. In the present study, the effect of chlorogenic acid on the inhibition of adipogenesis in 3T3-L1 adipocytes was investigated. Cells were stained with Oil red O reagent to detect lipid droplets in adipocytes. The 3T3-L1 cells were lysed and measured for intracellular triglyceride and adipokine by ELISA kit. The protein expression of adipogenesis-related gene was evaluated by Western blot analysis. Chlorogenic suppressed lipid droplet and intracellular triglyceride accumulation in a concentration manner and also decreased secretion of adipokines such as leptin and adiponectin, compared with fully differentiated adipocytes. Treatment of 3T3-L1 cells with chlorogenic acid reduced the protein levels of peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) and, CCAAT/enhancer binding proteins alpha ($C/EBP{\alpha}$). This indicates that chlrogenic acid was effective as an anti-obesity agent by repressing the differentiation of 3T3-L1 into adipocytes and inhibiting triglyceridef formation in adipocyte and that it exerts its role mainly through the significant down-regulation of $PPAR{\gamma}$ and $C/EBP{\alpha}$.

• Journal of Korean Biological Nursing Science
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• v.8 no.2
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• pp.41-59
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• 2006

Chronic liver diseases and hepatic cancer have been reported as 10% of cause of death in Koreans. Regardless of various causes, chronic liver disease accompanies commonly hepatic fibrosis. But still the mechanism of hepatic fibrosis remains poorly understood. Using the dimethylnitrosamine(DMN)-induced hepatic fibrosis rat model, We performed to evaluate the possible therapeutic effect of RIP(extracts of Phellodendron amurense and Patrinia scabiosaefolia) and to investigate the changes in referential connective tissue proteins($TGF-{\beta}_1$, ${\alpha}$-smooth muscle actin, and vimentin) as a marker of fibrogenesis. For these purposes, liver tissues were stained with H & E, and Azan staining for estimation of developing fibrosis. In the DMN-treated rat liver tissue, fibrosis were developed forming incomplete septal fibrosis. Whereas, in the RIP-treated rat liver tissues, the fibrosis were decreased recovering to normal morphology. The expressions of $TGF-{\beta}_1$, ${\alpha}$-smooth muscle actin($\alpha-SMA$), and vimetin were increased in the DMN-treated rat liver tissues, but decreased in the various areas of RIP-treated rat liver tissues. According to these results, RIP could be a possible therapeutic agent to reduce hepatic fibrosis, and the $TGF-{\beta}_1$, ${\alpha}$-SMA, and vimentin could be possible indicative markers of hepatic fibrosis development and recovery.

• Applied Microscopy
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• v.23 no.1
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• pp.35-55
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• 1993

cis-Dichlorodiammineplatinum (II) (cis-Platin), a metallic compound, has widely been used as an effective anticancer chemotherapeutic agent. The precise mechanism of action of this agent is still unknown, but it is postulated that cis-Platin may act on the cancer cell like bifunctional alkylating agents. Although this agent is very beneficial to the patients with cervical cancer, germinoma of testis, neuroblastoma and others, it may also damage to the normal cell so that many side effects; severe hemorrhagic enterocolitis, bone marrow depression, renal damage and liver damage will develope. This experiment has been undertaken to pursue the cytotoxic effects of the cis-Platin on the ultrastructures of the interalveolar septum in the mouse lung. A total of 55 healthy male mice of ICR strain were used as experimental animals and divided into 5 mice of normal control group and 50 mice of cis-Platin treated group. The mice of cis-Platin treated group were sacrificed by carotid exsanguination at 6, 12, 24 hours, 3 days and 7 days after intraperitoneal injection of 6.0 mg of cis-Platin ($Abiplatin^R$ Abic Co. Ltd.) per kg of mouse body weight. The specimen obtained from the lower lobe of left lung were sliced into $1mm^3$ and prefixed with 2% glutaraldehyde -2.5% paraformaldehyde solution prepared with Millonig's phosphatae buffer solution (pH 7.4) at $4^{\circ}C$ for 3-4 hours. After postfixation with 1% osmium tetroxide solution all specimens were embedded in Epon 812. Ultrathin sections about $600-800{\AA}$ in thickness were stained with uranyl acetate and lead citrate and observed with Hitachi-600 electron microscope. The results obtained were as follows: 1. Local swellings with increase of electron density and number of pinocytic vesicles in the cytoplasms of the type I pneumocyte and endothelial cell of the blood air barrier in interalveolar septum of cis-platin treated mice were observed. 2. Cisternae of rough endoplasmic reticulum were dilated and sacculated in association with detachment of membrane bound ribosomes of the type II pneumocyte in interalveolar septum of cis-Platin treated mice. 3. Swollon mitochondria with uneven electron density of their matrix were observed in the type II pneumocyte of interalveolar septum in the cis-Platin treated mice. 4. The lamellae of lammelar bodies in type II pneumocyte of interalveolar septum in cis-Platin treated mice were devoided or transformed into homogeneous electron dense material. It is consequently suggested that cis-Platin would induce the cellular edema of type I pneumocyte and endothelial cell, and degenerative changes of cytoplasmic organelles of the type II pneumocyte in the interalveolar septum of the mouse lung.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.1
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• pp.57-61
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• 2002

The renoprotective activities of white ginseng radix and rootlet were compared in spontaneously hypertensive rat (SHR) with diabetes. During oral administration of white ginseng radix (Ginseng Radix Alba, GRA) and white ginseng rootlet (Ginseng Radix Palva, GRP) for four weeks, arterial blood pressure and blood glucose levels were determined at every 10 days. In both GRA- and GRP-treatment groups, arterial blood pressures started to go down after 10 days of administration and maintained throughout the study period. After four weeks administrations of GRA and GRP, diastolic blood pressures were significantly decreased with 17% and 9%, respectively. GRA treatment also decreased blood glucose levels after 10 days of administration when compared with diabetic SHR group. At the end of the experiment, serum creatinine (Scr) and blood urea nitrogen (BUN) were not significantly different between the groups, except 62% higher value of BUN in diabetic SHR group when compared with SHR group. In the diabetic SHR group, the excretion of urinary albumin was increased significantly when compared with SHR. The level of urinary albumin in GRA treated group was markedly reduced when compared with diabetic SHR group $(67.8{\pm}4.7\;vs.\;131.3{\pm}13.5\;mg/24\;h).$ To examine the effects of ginseng radices on an overt diabetic nephropathy, index of kidney hypertrophy and transforming growth $factor-{\beta}1\;(TGF-{\beta}1)$ protein levels were evaluated. The glomerular and tubular cells stained positive for $TGF-{\beta}1$ seemed to be more abundant in diabetic SHR than in those with SHR, and GRA treated rats showed somewhat less $TGF-{\beta}1$ protein in glomerular and tubular cells when compared with diabetic SHR. Our results suggest that GRA might be a useful antihypertensive and antidiabetic agent with renoprotective effect.

• Biomedical Science Letters
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• v.16 no.4
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• pp.213-220
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• 2010

Although an adequete intake of calcium (Ca) is recommended for the treatment and prevention of osteoporosis, the intake of Ca should be restricted because of its low rate of intestinal absorption. The purpose of this experiment was to identity the effect of the combined administration of Aquamin F (AQF) (a calcium agent) and lactic acid bacteria (LAB) on osteoporosis. Thirty ovariectomized (OVX) rats and six control rats were assigned to the following six groups, with six animals per group: sham Ca-deficient diet (Ca-D), OVX, LAB, AQF, and LAB-AQF. During the experiment, the body weight was measured; and after the experiment was completed, the serum biochemical analysis, the alkaline phosphatase, calcium, and inorganic phosphorus leves were measured. The tissue of the femur was stained and then scanned via CT. The body weight of the OVX group increased more significantly than that of the control group. The results of the bone mineral content (BMC), Bone mineral density (BMD), serum biochemical analysis and histological test on the femur epiphysis showed no difference between the OVX group and the LAB group, whereas the results of the AQF group were more significant than those of the OVX group. In particular, the LAB+AQF group showed more significant increases in the aforementioned results than the AQF group. This experiment showed that the combined administration of AQF and LAB in ovariectomized rats more significantly increased bone density than did a single administration of either AQF or LAB.

• Molecular & Cellular Toxicology
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• v.2 no.2
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• pp.126-133
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• 2006

Thioacetamide (TA) is well known hepatotoxic and hepatocarcinogenic agent. TA also diminishes the contents of hepatic cytochrome P450 and inhibits the enzyme activity of the hepatic mixed function oxidases. TA metabolite, thioacetamide-s-oxide, is further transformed into a still unknown highly reactive metabolite that binds to macromolecules. In this study, we focused on TA-induced gene expression at hepatotoxic dose. Mice were exposed to two levels (5 mg/kg or 50 mg/kg i.p.) of TA, sampled at 6 or 24 h, and hepatic gene expression levels were determined to evaluate dose and time dependent changes. We evaluated hepatotoxicity by serum AST and ALT level and histopathological observation. Mean serum activities of the liver leakage enzymes, AST and ALT, were slightly increased compare to control. H & E and PAS evaluation of stained liver sections revealed TA-associated histopathological finding in mice. Centrilobular eosinophilic degeneration was observed at high dose-treated mice group. Hepatic gene expression was analyzed by QT clustering. Clustering of high dose-treated samples with TA-suggests that gene expressional changes could be associated from toxicity as measured by traditional biomarkers in this acute study.

• Toxicological Research
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• v.18 no.4
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• pp.369-374
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• 2002

The present study was performed to validate an automated image analysis system (Loats Automated Micronucleus Scoring System) for the mouse bone marrow micronucleus assay, comparing with conventional microscopic scoring. Two studies were conducted to provide slides for a comparison of micro-nucleated polychromatic erythrocytes (MNPCEs) values collected manually to those collected by the auto-mated system. Test article A was used as an example of a compound negative for the induction of micronuclei and test article B was wed as a micronucleus-inducing agent to elicit a positive response. Cyclophosphamide was included to provide an positive control in two studies. Bone marrow samples were collected 24 h after administration of test article A and B in male ICR mice. The cells were fixed with absolute methanol and stained with May-Grunwald and Giemsa. The number of MNPCEs was determined by the analysis of 1000 total PCEs per bone marrow sample. In addition to micronucleus scoring, an index of bone marrow toxicity based on PCE ratio (% of PCEs to total erythrocytes) was determined for each sample. The automated and manual scoring was similar when the MNPCEs incidence induced by each test article was less than 10. However manual scoring was able to effectively enumerate micronucleated PCEs in mouse bone marrow when MNPCEs incidence was more than 10, such as cyclophosphamide treatment. Conversely, PCE ratio was superior in computer-assisted image analysis. Taken together, it is suggested that improvement of the automated image analysis may be necessary to render the automatic scoring as sensitive as manual scoring for routine counting of micronuclei, especially because it is superior in objectivity and high throughput scoring.

• BMB Reports
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• v.38 no.4
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• pp.391-398
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• 2005

3-hydrogenwadaphnin (3-HK) is a new daphnane-type diterpene ester isolated from Dendrostellera lessertii with strong anti-tumoral activity in animal models and in cultures. Here, prolonged effects of this new agent on proliferation and viability of several different cancerous cell lines were evaluated. Using [$^3H$]thymidine incorporation, it was found that the drug inhibited cell proliferation and induced G1/S cell cycle arrest in leukemic cells 24 h after a single dose treatment. The cell viability of Jurkat cells was also decreased by almost 10%, 31% and 40% after a single dose treatment (7.5 nM) at 24, 48 and 72 h, respectively. The drug-treated cells were stained with acridine orange/ethidium bromide to document the chromatin condensation and DNA fragmentation. These observations were further confirmed by detection of DNA laddering pattern in the agarose gel electrophoresis of the extracted DNA from the treated cells. Treatment of K562 cells with the drug at 7.5, 15 and 30 nM caused apoptosis in 25%, 45% and 65% of the cells, respectively. Exogenous addition of $25-50\;{\mu}M$ guanosine and/or deoxyguanosine to the cell culture of the drug-treated cells restored DNA synthesis, released cell arrest at G1/S checkpoint and decreased the apoptotic cell death caused by the drug. These observations were not made using adenosine. However, the drug effects on K562 cells were potentiated by hypoxanthine. Based on these observations, perturbation of GTP metabolism is considered as one of the main reasons for apoptotic cell death by 3-HK.