• Oncology Letters
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• v.18 no.3
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• pp.3256-3264
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• 2019

The induction of apoptosis is a useful strategy in anti-cancer research. Various Moon Hyung Yang (MHY) compounds have been developed as novel anti-cancer drug candidates; in the present study, the pro-apoptotic effects of (Z)-5-(3-ethoxy-4-hydroxybenzylidene)-2-thioxothiazolidin-4-one (MHY695) on HCT116 human colon cancer cells were assessed. MTT assays were performed to investigate the dose-dependent cytotoxic effects of MHY695 on HCT116 cells. Immunofluorescence staining and flow cytometry analyses were performed to identify apoptotic cell death, and western blot analysis was used to investigate the apoptotic-signaling pathways. A mouse xenograft model was also used to determine the effects of MHY695 in vivo. MHY695 decreased the viability of HCT116 cells and induced apoptotic cytotoxicity. The apoptotic mechanisms induced by MHY695 involved the dephosphorylation of Bcl-2-associated agonist of cell death protein following protein kinase B inactivation, induced myeloid leukaemia cell differentiation protein and BH3-interacting domain death agonist truncation, caspase-3 and -9 activation and poly (ADP-ribose) polymerase cleavage. In addition, MHY695 significantly suppressed tumor growth in the mouse xenograft model, compared with the vehicle control. Notably, MHY695 exhibited potent anti-cancer effects in four different types of human colon cancer cell line, including Caco-2, DLD-1, HT-29 and HCT116. Additionally, MHY695 showed reduced cytotoxicity in NCM460, normal colonic epithelial cells. Furthermore, MHY-induced cytotoxicity in colon cancer cells was independent of the tumor suppressor protein p53. Collectively, these observations suggested that MHY695 may be a novel drug for the treatment of colon cancer.

• 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.

• Journal of fish pathology
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• v.17 no.1
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• pp.29-38
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• 2004

The effects of dietary $\beta$-1,3/1,6-linked glucan administration on nonspecific immune responses, hematology and disease resistance against Edwardsiella tarda in olive flounder, Paralichthys olivaceus were evaluated. Fish were fed the experimental diets supplemented with 0 %, 0.01 %, 0.05 %, 0.1 %, and 0.5 % of $\beta$-glucan to a commercial diet for 7 weeks. The test was performed in two ways such as fed on each $\beta$-glucan concentrations daily and every other week alternately. The body weight gain from the fish fed on daily the 0.05 % supplemented diet and fed on alternately the 0.1 % supplemented diet of $\beta$-glucan were significantly higher than the control. Both lysozyme activity and intracellular superoxide anion production of kidney phagocytes were higher in the all experimental groups than in the control. But there was no large difference in hematology among each group. The relative percent survival rate (RPS) after an artificial challenge with $4{\times}10^6$ cells of E. tarda per fish was higher than the control, except for that fed on daily the 0.01 % supplemented diet.

• The Korea Journal of Herbology
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• v.23 no.1
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• pp.75-83
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• 2008

Objectives : The present study was carried out to investigate the effect of Hyperici Japonici Herba on the proliferation and activation of eosinophils which were prepared from lung cells of asthma-induced mice by ovalbumin(OVA) treatment. Methods : C57BL/6 mouse was exposed to OVA three times a week for 6 weeks. The mouse lung tissues were dissected out, chopped and dessiciated with collagenase(1${\mu}g$/ml). Eosinophils were activated by rIL-3/rmIL-5 co-treatments. The lung cells were treated with extract of Hyperici Japonici Herba(EHH), incubated for 48 hr at $37^{\circ}C$, and analyzed by flow cytometer. ELBA, RT-PCR, immunocytochemistry stain. Results : The cell number ratio of granulocyte, $CD3e^-$/$CCR3^+$, $CD3e^+$/$CD69^+$, $CD4^+$, $CD23^+$/$B220^+$ cells was increased in rmIL-5/rIL-3 treated control group compared to the normal group. Cells numbers in the experimental animal group treated with EHH was all decreased. In ELISA analysis, IL-4, IL-5, IL-13 protein levels and histamine release level were greatly increased in the control group compared to the normal animal group, then significantly decreased in the experimental group with 100 ${\mu}g$/ml of EHH treatment. In RT-PCR analysis, the HT value of IL-4, IL-5, IL-13, CCR3, Eotaxin were increased in the control group compared to the normal animal group, then decreased in the experimental group with 100 ${\mu}g$/ml of EHH treatment. And eosinophil proliferation levels were 18847${\pm}$1527(cpm) in the control group, 4676${\pm}$972(cpm) in the positive control group, and 8675${\pm}$159(cpm), 11352${\pm}$1005(cpm), 14325${\pm}$677(cpm) in the experimental group with 100 ${\mu}g$/ml, 10 ${\mu}g$/ml, 1 ${\mu}g$/ml of EHH treatment. Conclusions : The present data suggested that Hyperici Japonici Herba may have an effects on the inhibition of parameters associated with asthma responses in eosinpophils, and thus implicate the possibility for the clinical application of EHH.

• Microbiology and Biotechnology Letters
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• v.10 no.2
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• pp.123-132
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• 1982

These experiments were conducted to investigate the enzymatic characteristics of the purified $\alpha$-amylase (F-2A) of Bacillus circulans F-2 and the digestion rate of various starches. 1. The molecular weight was estimated to be 93000 by SDS-polyacrylamide disc gel electrophoresis. The isoelectric point was about pH 5.0. The optimum pH for the enzyme action was 6.0-6.5 and the stable pH ranged pH 5.5-12.0. The optimum temperature was 6$0^{\circ}C$, and the purified $\alpha$-amylase was stable below 4$0^{\circ}C$. 2. The purified $\alpha$-amylase was activated by Mn$^{＋＋}$ and Co$^{＋＋}$, whereas it was inhibited by Ag$^{＋}$, HT$^{＋＋}$, Cu$^{＋＋}$ and Pb$^{＋＋}$. 3. The purified $\alpha$-amylase is considered to have no sulfhydryl residue essential for its catalytic activity. 4. Michaelis constant (Km) was 1.704 mg/$m\ell$. Activation energy between 25-4$0^{\circ}C$ was 12.297 Kcal/mole, and between 40-6$0^{\circ}C$, it was 7.831 Kcal/mole. 5. The hydrolysis product from soluble starch, amylose and amylopectin in the early stage of hydrolysis was G$_{6}$, and as hydrolysis proceeds, G$_4$and G$_2$appeared. 6. Products from each oligosaccarides are as follows: G$_4$longrightarrow G$_2$＋ G$_2$,G$_3$ ＋G$_1$,G$_{5}$longrightarrow G$_4$＋G$_1$,G$_{6}$longrightarrowG$_4$＋ G$_2$,G$_{7}$ G$_4$,G$_{8}$longrightarrow G$_4$＋G$_4$, 7. On raw potato starch, raw sago starch and raw yam starch, the purified enzyme exhibited a remarkably high digestion rate than Porcine pancreatic amylase and Streptococcus bovis amylase.

• The korean journal of orthodontics
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• v.37 no.3 s.122
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• pp.171-181
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• 2007

Objective: The present study was aimed at an analytical formulation of the micro-implant related torque as a function of implant size, i.e. the diameter and length, screw size, and the bony resistance at the implant to bone interface. Methods: The resistance at the implant to cancellous bone interface $(S_{can})$ was assumed to be in the range of 1.0-2.5 MPa. Micro-implant model of Absoanchor (Dentos Inc. Daegu, Korea) was used in the course of the analysis. Results: The results showed that the torque was a strong function of diameter, length, and the screw height. As the diameter increased and as the screw size decreased, the torque index decreased. However the strength index was a different function of the implant and bone factors. The whole Absoanchor implant models were within the safe region when the resistance at the implant/cancellous bone $(=S_{can})$ was 1.0 or less. Conclusion: For bone with $S_{can}$ of 1.5 MPa, the cervical diameter should be greater than 1.5 mm if micro-implant models of 12 mm long are to be placed. For $S_{can}$ of 2.0 MPa, micro-implant models of larger cervical diameter than 1.5 mm were found to be safe only if the endosseous length was less than 8 mm.

• Archives of Pharmacal Research
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• v.25 no.5
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• pp.685-690
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• 2002

The mitogen-stimulated serine/threonine kinase $p70^{S6k}$ plays an important role in the progression of cells from $G_0/G$_1$$ to S phase of the cell cycle by translational up-regulation of a family of mRNA transcripts family of mRNA transcripts which contain polypyrimidine tract at their 5 transcriptional start site. Here, we report that $p70^{S6k}$ was constitutively phosphorylated and activated to various degrees in serum-deprived AGS, A2058, HT-1376, MG63, MCF7, MDA-MB-435S, MDA-MB-231 and MB-157. Rapamycin treatment induced a significant dephosphorylation and inactivation of $p70^{S6k}$ in all cancer cell lines, while wortmannin, a specific inhibitor of PI3-K, caused a mild dephosphorylation of $p70^{S6k}$ in AGS, MDA-MB-435S and MB-157. In addition, SQ20006, methylxanthine phosphodiesterase inhibitor, reduced the phosphorylation of $p70^{S6k}$ in all cancer cells tested. Consistent with inhibitory effect of rapamycin on $p70^{S6k}$ activity, rapamycin inhibited [$^3H$]-thymidine incorporation and increased the number of cells at $G_{0}G_{1}$ phase. Furthermore, these inhibitory effects were accompanied by the decrease in growth of cancer cells. Taken together, the results indicate that the antiproliferative activity of rapamycin might be attributed to cell cycle arrest at $G_{0}G_{1}$ phase in human cancer cells through the inhibition of constitutively activated $p70^{S6k}$ of cancer cells and suggest $p70^{S6k}$ as a potential target for therapeutic strategies aimed at preventing or inhibiting tumor growth.

• Journal of the Korean Society of Food Science and Nutrition
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• v.34 no.6
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• pp.797-804
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• 2005

Physiological activity of citrus essential oil (CEO) was determined to examine possible use of the food processing by-product as a functional material for food and cosmetic composition. The effect of gamma irradiation on the change of physiological activity also investigated at 0, 10 and 20 kGy. Limonene contents of CEO was $88.3\pm1.30\%$. Electron donating ability of CEO was $69\%$. Lipid oxidation was retarded by CEO. CEO showed antimicrobial activity against 1 yeast,4 molds and 4 bacteria species tested. More than $80\%$ of inhibition of cancer cell growth was presented by CEO using A549, HT29, HepG2, B16F10 and G361 cells at a 500 ppm level. Irradiation of CEO did not affect any physiological functions. A Salmonella mutagenicity assay indicated that the 20 kGy irradiated CEO did not show any mutagenicity Therefore, CEO, which is a major by-product in citrus processing, could be used as a functional material in various application.

• Journal of Oriental Neuropsychiatry
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• v.15 no.1
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• pp.43-64
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• 2004

The aim of this study was to evaluate the effects of Jowiseungcheongtang compared with St. John's wort in the chronic mild stress(CMS) animal model of depression. Wistar rats were used for this study. The subjects were divided into 4 groups (Naive group: without CMS procedure, CMS-vehicle: water was administered during CMS procedure, CMS-Jowiseungcheongtang: Jowiseungcheongtang was administered after 5 weeks of CMS procedure, CMS-St. John's wort: St. John's wort was administered after 5 weeks of CMS procedure) During 9 weeks of CMS procedure, The change of the consumption of sucrose and the changes of weights were measured. After CMS procedure, Morris water maze test, open field test, elevated plus maze test and Western blotting were measured. The results were as follows. 1. The consumption of sucrose solution was significantly reversed in Jowiseungcheongtang group and relatively reversed in St. John's Wort group at 7 week. 2. In open field test, Neither Jowiseungcheongtang nor St. John's wort group showed statistically significant change of exploratory activity. In EPM test, St. John's Wort group showed significant decrease of total arm entry in comparison with Naive group. And Jowiseungcheongtang group was showed no significant change. 3. In Morris water maze test, St. John's Wort group showed significant increase in escape latency of the last Morris water maze trial. And in water maze probe test, there was no significant change. 4. St. John's Wort group showed relative increase in LP1 division of 5HT1A receptor compared with Naive group. Both St. John's Wort and Jowiseungcheongtang group showed relative increase in P2 division of GluRl compared with Naive group. These results suggest that Jowiseungcheongtang is as effective as St. John's Wort in the treatment of depression.

• Archives of Pharmacal Research
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• v.21 no.5
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• pp.581-590
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• 1998

We developed a novel water-soluble camptothecin analobue, CKD602, and evaluated the inhibition of topoisomerase I and the antitumor activities against mammalian tumor cells and human tumor xenografts. CKD602 was a nanomolar inhibitor of the topoisomerase I enzyme in the cleavable complex assay. CKD602 was found to be 3 times and slightly more potent than topotecan and camptothecin as inhibitors of topoisomerase, respecitively. In tumor cell cytotoxicity, CKD602 was more potent than topotecan in 14 out of 26 human cancer cell lines tested, while it was comparable to camptothecin. CKD602 was tested for the in vivo antitumor activity against the human tumor xenograft models. CKD602 was able to imduce regression of established HT-29, WIDR and CX-1 colon tumors, LX-1 lung tumor, MX-1 breast tumor and SKOV-3 ovarian tumor as much as 80, 94, 76, 67, 87% and 88%, respectively, with comparable body weight changes to those of topotecan. Also the therapeutic margin (R/Emax: maximum tolerance dose/$ED-{58}$) of CKD602 was significantly higher than that of topotecan by 4 times. Efficacy was determined at the maximal tolerated dose levels using schedule dependent i.p. administration in mice bearing L1210 leukemia. On a Q4dx4 (every 4 day for 4 doses) schedule, the maximum tolerated dose (MTD) was 25 mg/kg per administration, which caused great weight loss and lethality in <5% tumor bearing mouse. this schedule brought significant increase in life span (ILS), 212%, with 33% of long-term survivals. The ex vivo antitumor activity of CKD602 was compared with that of topotecan and the mean antitumor index (ATI) values recorded for CKD602 were significantly higher than that noted for topotecan. From these results, CKD602 warrants further clinical investigations as a potent inhibitor of topoisomerase I.