• Genomics & Informatics
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• v.14 no.4
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• pp.255-264
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• 2016

The plethora of genome sequence information of bacteria in recent times has ushered in many novel strategies for antibacterial drug discovery and facilitated medical science to take up the challenge of the increasing resistance of pathogenic bacteria to current antibiotics. In this study, we adopted subtractive genomics approach to analyze the whole genome sequence of the Fusobacterium nucleatum, a human oral pathogen having association with colorectal cancer. Our study divulged 1,499 proteins of F. nucleatum, which have no homolog's in human genome. These proteins were subjected to screening further by using the Database of Essential Genes (DEG) that resulted in the identification of 32 vitally important proteins for the bacterium. Subsequent analysis of the identified pivotal proteins, using the Kyoto Encyclopedia of Genes and Genomes (KEGG) Automated Annotation Server (KAAS) resulted in sorting 3 key enzymes of F. nucleatum that may be good candidates as potential drug targets, since they are unique for the bacterium and absent in humans. In addition, we have demonstrated the three dimensional structure of these three proteins. Finally, determination of ligand binding sites of the 2 key proteins as well as screening for functional inhibitors that best fitted with the ligands sites were conducted to discover effective novel therapeutic compounds against F. nucleatum.

• Korean Journal of Microbiology
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• v.45 no.2
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• pp.177-184
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• 2009

Three hundred lactic acid bacteria isolated from human feces were studied their probiotic characters to develop potential probiotics. The properties were tested on the basis of guideline for probiotic selection protocol such as tolerance for acid or bile salt, thermal stability, antimicrobial, anticancer cell, and antiviral activity. Strain Miny-148 was selected as a potential probiotic bacterium which showed resistance to low pH, bile salts and thermal stability. On the basis of fatty acid profiles and 16S rDNA sequences analysis, the strain was identified as Lactobacillus pentosus (similarity 99.9%). The strain, L. pentosus Miny-148, showed broad antimicrobial spectrum against E. coli O157:H7, Shigella flexneri, Bacillus anthracis, Staphylococcus aureus, E. coli, Vibrio cholerae, V. vulnificus, Salmonella typhimurium, and Methicillin-resistant S. aureus (MRSA). Cell-free culture supernatant of the strain also inhibited against the growth of HT-29 colon cancer cell and transmissible gastroenterits virus.

• Journal of Life Science
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• v.19 no.5
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• pp.633-638
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• 2009

We investigated the inhibitory effects of solvent extracts from dried tuna on the growth of cancer cell lines (HT1080 human fibrosarcoma and HT-29 human colon cancer cells) and $H_2O_2$-induced oxidative stress. Inhibitory effects of acetone with methylene chloride (A+M) and methanol (MeOH) extracts on the growth of HT1080 and HT-29 cancer cells increased in a dose dependent manner (p<0.05). The inhibitory effect was more significant on the growth of HT1080 cells, and A+M extracts had a higher inhibitory effect compared to MeOH extracts. The treatments of hexane, 85% aq. methanol, butanol and water fractions significantly inhibited the growth of both cancer cells (p<0.05). Among the fractions, hexane and 85% aq. methanol fractions showed higher inhibitory effects. In order to determine the protective effect on $H_2O_2$-induced oxidative stress, a DCHF-DA (dichlorodihydrofluorescin diacetate) assay was conducted. All fractions, including crude extracts of dried tuna, appeared to significantly reduce the levels of intracellular reactive oxygen species (ROS) with dose responses (p<0.05). Among the fractions, BuOH and 85% methanol fractions showed a higher protective effect on the production of lipid peroxides. These results indicate that the consumption of tuna may be recommended as a potent functional food for preventing cellular oxidation and cancer.

• The Korean Journal of Nuclear Medicine
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• v.22 no.1
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• pp.83-92
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• 1988

The cocktails of two $^{131}I$ labeled Monoclonal antibody (MCAB) (Anti CA 19-9 F$(ab')_2$ + Anti CEA $F(ab')_2$ fragment), which react specially, with human gastrointestinal cancers, were administered to 10 patients with colorectal (7), stomach(2) and pancreas(1) cancer for scintigraphic detection. All patients were known or postoperatively recurrent cases, and serum tumor markers, CA 19-9 and CEA, were measured with immunoradiometric assay, just before immunoscintigraphy (ISG). The tumor marker's level in serum is not correlated with positive tumor uptake in ISG. The sensitivity and specificity of ISG in detection of 21 tumor sites, based on surgery, CT, ultrasonography and pathology, were 90.5% and 100% One case of colon cancer showed gall bladder metastasis, which was neglected on CT study. Tumor/non tumor uptake ratio of radiolabelled antibody were progressively increased from day 3 to day 7 during study. We summerized as follows 1) The use of cocktails of CEA and CA 19-9 MCAB $F(at')_2$ increased sensitivity and specificity in ISG. 2) Delayed imaging (later than 5 days) increases sensitivitv and specificity due to exclusion of nonspecific iodine accumulation in stomach and lung. 3) Second tracer technique is essential for anatomical landmark by use of a double isotope scan, but subtraction technique, a possible source of artifacts, is no longer necessory when delayed imaging is performed. 4) It may be possible to use two MCAB cocktails of CA 19-9 and CEA in Radioimmunodetection of stomach and pancreas cancer. In conclusion, ISG using MCAB cocktails, $F(ab')_2$ fragment of anti CA 19-9 and Anti CEA, provide additional opportunity for tumor localization and detection of colorectal and other G-I cancer, such as stomach and pancreas.

• Environmental Mutagens and Carcinogens
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• v.22 no.2
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• pp.65-69
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• 2002

To elucidate the effect of microsphere coinjection on the administration of oligodeoxynucleotides (ODN), we have investigated biodistribution of ［S-35］-labeled antisense ODN targeted to cAMP-dependent protein kinase (PKA) RI-$\alpha$ subunit in nude mice xenografted with WiDr (human colon cancer, ATCC CCL218). The strategy of using microsphere has been proposed for cancer treatment as a carrier of therapeutic ODN so that it could offer an advantage with respect to maintaining constant ODN levels in blood and obtaining higher therapeutic ODN concentration at tumor sites. Comparative biodistribution studies were performed in nude mice (female, 20 g of body weight, n = 4-6) xenografted with WiDr cancer cells, when 0.1 $\mu$Ci (specific activity, 2.94 mCi/$\mu$mole) of ［S-35］-labeled RI-$\alpha$ antisense ODN was injected alone or with microsphere (PLG-18, polylactic copolymer with cationic surfactant DDAB18). Peak tumor uptake of ［S-35］-labeled ODN was significantly increased from 17.7% (at 6 h) of injected dose per gram of tissue (ID/g) to 42.5% (at 24 h) ID/g when microsphere was coinjected with ODN. The different biodistribution in the kidney accumulation (e.g., 100.2% ID/g for ODN alone and 54.9%/ID/g for microshpere coinjection) may contribute to higher blood concentration (e.g., 21.5%ID/$m\ell$ for ODN alone and 37.5%ID/$m\ell$ for microsphere coinjection) of radiolabeled ODN. Of importance is the fact that the whole body retention of radioactivity increased with microsphere coinjection from 50.8%ID/g to 68.0%ID/g after 24-h of injection. This decreased kidney accumulation and increased whole body retention of ［S-35］-labeled ODN resulted in a significant improvement of ODN targeting to the tumor site. In conclusion, the coinjection of microsphere appears to be an important carrier system in vehiculation of antisense oligonucleotide to the tumor tissue in vivo.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.7
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• pp.1022-1028
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• 2013

Chaga mushroom (Inonotus obliquus) was considered a functional food with an anti-cancer effect in colon, gastric, and lung cancer. Therefore, this study was conducted in order to elucidate the effect of chaga mushroom extract in brain cancer. Glioblastoma U-87 MG cells were used in investigation of cell survivability, apoptosis, and cell cycle arrest analysis. Treatment with various concentrations of chaga mushroom extract resulted in inhibition of cell proliferation and cell cycle arrest. Although caspase-3 expression was increased over $100{\mu}g/mL$ of chaga mushroom extract treatment, apoptosis factors with Bcl-2, Bax and p53 did not change. In analysis of cell cycle regulatory factors, expression of cyclin D1 and CDK2 decreased in a dose-dependent manner. We have demonstrated the anti-cancer effect of chaga mushroom extract in glioblastoma, which may be mediated by activation of the caspase pathway and induction of cell cycle arrest.

• Journal of Ginseng Research
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• v.44 no.2
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• pp.282-290
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• 2020

Background: Ginseng is a commonly used herbal medicine in treating various medical conditions. Chronic gut inflammation is a recognized factor for the development of colorectal cancer (CRC). In this project, Asian ginseng berry polysaccharide preparations were used to assess their effects on CRC and related immune regulation mechanisms. Methods: Ginseng berry polysaccharide extract (GBPE) and purified ginseng berry polysaccharide portion (GBPP) were used to evaluate their activities on human HCT-116 and HT-29 CRC cell proliferation. Interleukin-8 secretion analysis was performed on HT-29 cells. Naive CD4 cell isolation and T-helper cell differentiation were performed and determined using flow cytometry for Th1 and Treg in addition to cell cycle and apoptotic investigation. Results: GBPE and GBPP significantly inhibited interleukin-8 secretion and cancer cell proliferation, inhibited CD4⁺IFN-γ⁺ cell (Th1) differentiation, and decreased CD4⁺FoxP3⁺ cell (Treg) differentiation. Compared to the GBPE, GBPP showed more potent antiinflammatory activities on the malignant cells. This is consistent with the observation that GBPP can also inhibit Th1-cell differentiation better, suggesting that it has an important role in antiinflammation, whereas Treg cells hinder the body's immune response against malignancies. Supported by cell cycle and apoptosis data, GBPE and GBPP, at various degrees, remarkably enhanced the anticancer activities of 5-fluorouracil. Conclusion: Data from this project suggested that Asian ginseng berry potentially has clinical utility in managing enteric inflammation and suppressing CRC through immunomodulation mechanisms.

• Korean Journal of Food Science and Technology
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• v.34 no.3
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• pp.505-509
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• 2002

In the course of screening program for VHR DS-PTPase (dual-specificity protein tyrosine phosphatase) from natural sources, Gastrodia elata was selected. One compound showing potent inhibitory activity was isolated by the solvent extraction and column chromatography including silica gel, ODS RP-18, Sephades LH-20, and HPLC. This compound was identified as baicalein by several NMR techniques such as $^1H-NMR$, $^{13}C-NMR$, and DEPT. Baicalein showed selective inhibitory activity against VHR DS-PTPase with $IC_{50}=2.4\;{\mu}M$, and showed cytotoxicity against several human cancer cell lines with an $GI_{50}$ of $5.26{\sim}12.93\;{\mu}g/mL$ range, including, melanoma (LOX-IMVI), lung cancer (NCI H23 and A549), colon cancer (HCT 116 and SW 620), prostate cancer (PC-3), and leukemia (MOLT 4F).

• Korean Journal of Microbiology
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• v.42 no.4
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• pp.319-325
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• 2006

[ $\beta$ ]-Glucans (AG) were prepared from Agaricus blazei cultured in the medium fortified with the roots of Pueraria spp. by repeated extraction with hot water, gel filtration chromatography and DEAE ion exchange chromatography. Oligosaccharides (AO) were derived from the hydrolysis of AG by an endo-$\beta$-(1$\rightarrow$6)-glucanase from Bacillus megaterium. The anti-HT-29 human colon cancer activity of AG or AO was investigated using MTT assay, apoptosis assay, cell cycle analysis, and cDNA microairay. AG and AO both inhibited proliferation and growth of HT-29 cells, and stimulated apoptosis of the cells in a dose-dependent manner. In cell cycle analysis, treating HT-29 cells with AG or AO resulted in the increase of cells in the G0 (sub-G1) and G1 phase. Especially, AO was more effective in inducing G0/G1 cell cycle arrest than AG. To screen the genes involved in the increase of apoptosis, the gene expression profile of the HT-29 cells treated with AO was examined by cDNA microarray. While several genes involved in cell cycle progression (CCND2 and CDK2) were down-regulated, many genes involved in apoptosis (TNFSF9, TNFRSF9, FADD, CASP8, BAD, CRADD, CASP9 etc), cell cycle inhibitor (CDKN2A), immune response (IL6, IL18, IL6R etc), and tumor suppressor (CEACAM1, TP53BP2, IRF1, and PHB) were up-regulated. These results suggest that AO could inhibit the proliferation and growth of HT-29 cells by G0/G1 cell cycle arrest and induction of apoptosis.

• Applied Biological Chemistry
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• v.49 no.3
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• pp.227-232
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• 2006

Styela clava (also called as rough sea squirt or leathery tunicate) is regarded as native to the northwest Pacific region including Korea and widely distributed in parts of northwestern Europe, North America and Australia. To evaluate Styela clava as a potential bioactive agent, the antioxidant activity of aceton extracts from Styela clava (whole, substance and tunic) was tested by measuring inhibitory effect of $H_2O_2$ induced DNA damage using comet assay. Also, anticancer activity on human colon cancer cell (HT-29) was investigated by MTT reduction assay. The $200\;{\mu}M$ $H_2O_2$ induced DNA damage was inhibited with Styela clava aceton extract in dose dependent manner in human leukocytes. The maximum inhibition was by 62.8, 62.1 and 78.3% at the concentration of $50\;{\mu}g/ml$ of whole, substance and tunic extracts, respectively. The aceton extracts from S. clava were also found to inhibit the growth of human colon cancer cell. The cell proliferation rates decreased to 26.9, 30.6 and 12.0% at the concentration of $500\;{\mu}g/ml$ of whole, substance and tunic extracts, respectively. These results support that aceton extracts from S. clava may be a potential candidate as a possible antimutagenic and chemotherapeutic agent.