• Korean Journal of Veterinary Service
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• v.29 no.3
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• pp.347-364
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• 2006

This study is concerned with assessment of diethylnitrosamine (DEN 0.01 %) induced liver cell carcinogenesis by measurement of changes preceding the development of neoplasms. Therefore, it was undertaken to investigate changes of liver-specific enzyme activities in Sprague-Dawley (SD) rats by ad libitum feeding of DEN. And also. the changes of hepatic morphology in SD rats were detected by haematoxylineosin stain and immunohistochemistry (PCNA). 5- Fluorouracil (5- FU) is one of the most widely used anticancer agents for digestive cancers including hepatocellular carcinoma, and is known to affect the cell cycle and induce apoptosis of cancer cells. In the present study, SD rats were given drinking water containing 0.01% diethylnitrosamine (DEN) for 8 weeks. Minor behavioral change, brittleness of hair and decreased amount of water and diet intake were observed in rats 4 weeks after DEN administration. The body and liver weights were significantly (p < 0.05) decreased in rats 11 weeks after DEN administration. The liver weight ratio to body weight was rather stable and not significantly decreased in the all treatment groups. The liver specific enzyme activities (AST, ALT, ${\gamma}$-GTP) were significantly increased in all treatment groups compared to control group (p < 0.05). Variable size of liver tumor and hepatomegaly were observed in rats treated with DEN after 10 weeks. Numerous vacuoles were seen on the midzonal and or peripheral areas of hepatic lobules. The large and polymorphological hepatocytes with eosinophilic cytoplasm or densely basophilic mitotic nucleoli were seen. Several proliferative small round cells were seen on vacuolated and necrotic areas in peripheral hepatic lobules or portal areas. PCNA-positive cells were seen on the vacuolated portal areas and peripheral areas of hepatic lobules in the areas of small round cells. We examined functional and morphological changes of livers by 5 - FU treatments on DEN -treated rat. The DEN -treated rats compared to 5 - FU -treated rats after DEN treatment for 8 weeks. The serum total protein and triglyceride were significantly (p < 0.05) decreased, and the liver enzyme activities of AST and ALT were significantly(p < 0.05) increased. After 8 weeks, in the non-5-FU -treated group, the size of liver tumor were varied and hepatomegaly were observed, hepatocellular vacuolization, necrosis and steatosis were observed on the midzonal and peripheral areas of hepatic lobules. The large and polymorphological hepatocytes were seen, the interlobular connective tissues were proliferated. PCNA positive cells were seen in the portal areas and peripheral areas of hepatic lobules in the non-5-FU-treated group. In hepatocytes, condensation of nuclear chromatin and vacuolization were observed, shape of the nuclei were irregular, the degraded nuclei and organelles were observed. The livers of rats in the 5 - FU treatment group were seen grossly brilliant, red-brown color, and the vacuolated and degenerated regions, hyperplastic nodules were not nearly observed. In the electron microscope, the cytoplasm of the hepatocytes contained a large number of mitochondria, rough endoplasmic reticulum, developed organelles surrounding nuclei. The above findings suggest that 5 - FU will be effective as anti -liver tumor drug.

• Applied Biological Chemistry
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• v.49 no.2
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• pp.91-96
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• 2006

Antioxidant activities and biological properties such as antimutagenic and cytotoxic effect of Phellinus linteus extracts from different extraction conditions were measured against Salmonella typhimurium and human cancer cell lines. DPPH free radical scavenging activities of the extracts were higher in the solutions extracted with ethanol (17.14) and ethanol after water (17.79), respectively. In the Ames test, ethanol extract of P. linteus alone did not exhibit any mutagenicity but showed substantial inhibitory effect against mutations induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), 4-nitroquinoline-1-oxide (4NQO), and benzo $({\alpha})$ pyrene $(B({\alpha})P)$. The extracts of ethanol and ethanol after water of P. linteus $(200\;{\mu}g/plate)$ had the highest inhibitory effect of 61.5 and 60.9%, respectively, on the mutagenesis on S. typhimurium TA98 strain induced by $B({\alpha})P$. Extracted solutions of ethanol and ethanol after water of P. linteus showed high antimutagenic effect against MNNG, 4NQO, Trp-P-1 and $B({\alpha})P$, causing mutations in S. typhimurium TA100 strain. The anticancer effects of P. linteus extracts were investigated against human fibrosarcoma HT-29 and human hepatocellular carcinoma HepG2. The treatment of 0.5 mg/ml of ethanol, ethanol after water and water extracts of P. linteus had the highest cytotoxicity of 59, 57, 54%, respectively against HT-27 cell line, whereas low cytotoxicity effects were observed against HepG2 cell line in the range of $10{\sim}30%$. The ethanol and water extracts of P. linteus also showed the nitrate scavenging ability at different pHs. The ethanol extract showed higher nitrate-scavenging ability compared to water extract of P. linteus.

• The Korean Journal of Food And Nutrition
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• v.28 no.4
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• pp.594-601
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• 2015

In the present study, the total content of polyphenols and flavonoids, the antioxidant activities, and cytotoxic effects of the ethanol extracts from different parts of Taraxacum coreanum Nakai were investigated for their use as functional foods. The extract yields of the flower, leaf, and root were $32.15{\pm}3.21%$, $31.63{\pm}0.63%$, and $27.48{\pm}2.47%$, respectively. Total polyphenol and flavonoid content of the flower extract were $61.29{\pm}2.11mg/g$ and $46.11{\pm}1.88mg/g$, respectively, which were much higher than those of any other plant parts. The antioxidant activities of the flower, leaf, and root extracts were $89.99{\pm}2.83%$, $85.29{\pm}2.22%$, and $37.88{\pm}2.34%$, respectively, at a concentration of 1.0 mg/mL. Cell cytotoxicity effects of AGS (human gastric carcinoma), HCT116 (human colon carcinoma), and A549 (human pulmonary carcinoma) cells were the highest in the flower extract, with values of $62.85{\pm}4.63%$, $69.89{\pm}3.44%$, and $85.72{\pm}4.17%$, respectively, at a concentration of 400 mg/kg. Both the antioxidant activities and cytotoxic effects of the ethanol extracts from all the parts of the T. coreanum Nakai increased dose-dependently. These results provide preliminary data for the development of T. coreanum Nakai as an edible functional food material.

• Journal of Life Science
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• v.27 no.9
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• pp.1020-1030
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• 2017

Epidemiology studies have reported a reduced incidence of colon cancer among populations that consume a large quantity of ${\omega}3-polyunsaturated$ fatty acids (${\omega}3-PUFAs$) of marine origin. Herein, we demonstrated a mechanism of anticancer action of ${\omega}3-PUFAs$, showing that they suppressed invasion and tumorigenicity in colon cancer cells. Docosahexaenoic acids (DHA) inhibited the cell growth of HT29 cells. This action likely involved apoptosis, given that the DHA treatment increased the cleaved form of PARP and sub G1 cells. Moreover, the invasiveness of HT29 cells was inhibited following DHA treatment, whereas arachidonic acid (AA) had no effect. The levels of Matrix-metalloproteinase-9 (MMP-9) and MMP-2 mRNA decreased after DHA pretreatment. DHA treatment inhibited MMP-9 and MMP-2 promoter activities and reduced VEGF promoter activity. DHA pretreatment also inhibited the activities of prostaglandin-2 (PGE2)-induced MMPs and the VEGF promoter. Cyclooxygenase-2 (COX-2) overexpression increased the activity of MMPs and that of the Vascular endotherial growth factor (VEGF) promoter in HT29 cells, and DHA inhibited NF-kB and COX-2 promoter reporter activities. As shown by in vivo experiments, when mouse colon cancer cells (MCA38) were implanted into Fat-1 and wild-type mice, both the tumoral size and volume were dramatically inhibited in Fat-1 transgenic mice. Furthermore, TUNEL-positive cells increased in tumors from Fat-1 mice compared with wild mice. In immunohistochemistry, the intensity of CD31 in Fat-1 tumors was weaker. These findings suggest that ${\omega}3-PUFAs$ may inhibit tumorigenicity and angiogenesis as well as cancer cell invasion by suppression of COX-2, MMPs and VEGF via the reduction of NF-kB in colon cancer.

• Journal of Yeungnam Medical Science
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• v.12 no.1
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• pp.32-47
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• 1995

Glutathione(GSH) has a very important role in detoxification of cells and is closely related to antitumor drug-resistance of cancer cells. In order to evaluate the importance of glutathione metabolism in the drug-resistant cancer cells, the concentration of celluar GSH and activities of ${\gamma}$-glutamylcysteine synthetase(GCS), ${\gamma}$-glutamyl transpeptidase (GGT) and glutathione S-transferases(GST) in the adriamycin, vincristine, or cisplatin resistant L1210 (L1210AdR, L1210VcR, or L1210Cis) sublines were measured. Expression and amplification of GCS, GGT, and GST-${\pi}$ genes were also observed in the parent Ll210 and the drug-resistant Ll210 sublines. The concentration of GSH was increased 5.34 fold in L1210Cis, 2.83 fold in L1210VcR, and 1.78 fold in L1210AdR, compared to L1210. The activities of GCS and GGT were increased in drug-resistant L1210 sublines. The GST activity was increased in L1210VcR and L1210Cis but decreased in L1210AdR compared to Ll210. Expression of GCS, GGT, and GST-${\pi}$ genes were increased in the resistant L1210 sublines compare to the parent L1210 in northern blot analyses. Overexpression of GCS, GGT, and GST-${\pi}$ were observed in the resistant sublines, and the increases of the concentration of glutathione and the activities of GCS and GGT in the resistant sublines may be involved in a part of the drug-resistance in the resistant sublines.

• Food Science and Industry
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• v.53 no.1
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• pp.2-32
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• 2020

In recent years, significant importance has been given to chitooligosaccharides (COS) due to its potent notable biological applications. COS can be derived from chitosan which is commonly produced by partially hydrolyzed products from crustacean shells. In order to produce COS, there are several approaches including chemical and enzymatic methods which are the two most common choices. In this regard, several new methods were intended to be promoted which use the enzymatic hydrolysis with a lower cost and desired properties. Hence, the dual reactor system has gained more attention than other newly developed technologies. Enzymatic hydrolysis derived COS possesses important biological activities such as anticancer, antioxidant, anti-hypersentive, anti-dementia (Altzheimer's disease), anti-diabeties, anti-allergy, anti-inflammatory, etc. Results strongly suggest that properties of COS can be potential materials for nutraceutical, pharmaceutical, and cosmeceutical product development.

• Korean Journal of Ichthyology
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• v.26 no.3
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• pp.171-178
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• 2014

Myogenesis is the formation process of multinucleated myofiber with a contractile capacity from muscle satellite cell (MSCs) during life. This process is tightly controlled by several transcription factors such as Pax3 and Pax7 (paired box protein 3 and 7), MEF2C (myocyte enhancer factor 2) and MRFs (myogenic regulatory factors) etc. On the contrary, myostatin (MSTN) is a transforming growth factor-${\beta}$ superfamily, which functions as a negative regulator of skeletal muscle development and growth. Carnosic acid (CA) is a major phenolic component in rosemary (Rosmarinus officinalis) and have been reported various biological activities such as anticancer, antioxidant, antimicrobial and therapeutic agents for amnesia, dementia, alzheimer's disease. This study was confirmed to effects of CA on muscle cell line and muscle tissue alteration of zebrafish by intramuscular injection or feeding methods. $10{\mu}M$ CA showed a non-cytotoxic on myoblast and a complete inhibition effect against myostatin activity on luciferase assay. In intramuscular injection experiment, the total protein and triglyceride amount of $10{\mu}M/kg$ of CA injected group increased by 11% and decreased by 13% compared to these of the no injected group. In histology analysis of muscle tissues by hematoxylin/eosin staining, the number of muscle fiber of $10{\mu}M/kg$ of CA injected group decreased by 29% and fiber area increased 40% compared to these of no injected group. In feeding experiment, the total protein and triglyceride amount no significance difference compared to these of the normal feeding group. In histology analysis, the number of muscle fiber of 1% CA fed group decreased by 35% and fiber area increased 56% compared to these of normal fed group. We identified that CA have an effect on hypertrophy of muscle fiber in adult zebrafish and the results of this study are considered as the basic data that can reveal the mechanisms of muscle formation via gene and protein level analysis.

• Journal of Ginseng Research
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• v.25 no.4
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• pp.156-161
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• 2001

We investigated the effects of polyacetylenes of ginseng on farnesyl protein transferase (FPTase) and carboxyl methyl transferase (CMTase) activities related to post-translational modification of Ras protein. We also investigated the effect of petroleum ether extract (PEE) of ginseng on progression of cell cycle. FPTase activity was respectively inhibited 16.2% by 10mM panaxynol and 21.3% by 10mM panaxydol, whereas CMTase activity was not inhibited by panaxynol or panaxydol. Treatment of PEE significantly reduced the numbers and size of human colon cancer cell (HT-29) and human liver cancer cell(HepG2) cultured, respectively. To investigate the mechanism of growth inhibition by PEE of ginseng, we analyzed the cell cycle progressions of PT-29 and HepG2 cells, respectively. We found that PEE significantly inhibited progression of cell cycle from G1 to S phase. These results suggest that anticancer effects of PEE were derived from the arrest of G1 phase in cell cycle progression.

• Journal of Life Science
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• v.23 no.9
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• pp.1126-1132
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• 2013

Cytochrome P450 2J2 (CYP2J2) is an enzyme mainly found in human extrahepatic tissues, with predominant expression in the cardiovascular system. CYP2J2 plays important roles in the metabolism of endogenous metabolites and therapeutic drugs, such as arachidonic acid, astemizole, ebastine, and terfenadine. CYP2J2 is also overexpressed in human cancer tissues and cancer cell lines and may represent a potential target for therapy of human cancers. In this study, 10 natural products obtained from plants and microorganisms were screened as potential CYP2J2 inhibitors. Among them, thelephoric acid showed strong inhibition of astemizole O-demethylation activity ($IC_{50}=3.23{\mu}M$) in a dose-dependent manner. Evaluation of the substrate dependency of the inhibitory activity of thelephoric acid showed that it strongly inhibited CYP2J2-mediated ebastine hydroxylation ($IC_{50}=5.32{\mu}M$) and terfenadine hydroxylation ($IC_{50}=3.27{\mu}M$) in a substrate nondependent manner. The present data suggest that this compound might be a potential candidate for further evaluation for anticancer activity.

• Journal of Applied Biological Chemistry
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• v.55 no.3
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• pp.157-161
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• 2012

The aim of this research was to investigate the industrial application of Sedum sarmentosum. Antibacterial activities of the n-hexane, methylene chloride (MC), ethyl acetate, and n-butanol fractions of S. sarmentosum were tested against Escherichia coli, Staphylococcus aureus, and Helicobacter pylori. The MC fraction showed the strongest antibacterial activity against E. coli, with an inhibition zone greater than 13 mm in disc assays. At $100{\mu}g/mL$, all fractions scavenged more than 50% of 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radicals (${\cdot}OH$). In particular, the MC fraction showed the strongest scavenging activity against DPPH and ${\cdot}OH$. In addition, we found that treatment with the MC fraction inhibited the growth of H. pylori and gastric adenocarcinoma cells. The present results suggest that the MC fraction of S. sarmentosum would play the promising protective role against pathogenic bacteria and free radicals.