• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.81-81
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• 2003

The present study was taken to examine the inhibitory effect of extracts of Scytosiphon lomentaria, a marine alga growing in Jeju Island, on the growth of cancer cells and to develop an anti-cancer agent using components of S. lomemtaria. The effect was observed by the measurement of metabolic activity using colorimetric 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide (MTT) assay. In results, crude extract of this alga markedly inhibited the growth of leukemia cell lines such as HL-60 and KG-1, but could scarcely inhibit the growth of normal cells (HEL299) and adenocarcinoma cells (SNU-16 and HCT-I5). When HL-60 cells were treated with the extract, DNA fragmentation and the increase of proportion of sub-G1 hypodiploid cells were observed. Therefore, the inhibitory effect of S. lomemtaria on the growth of HL-60 cells seems to arise from the induction of apoptosis. In order to understand the mechanism of apoptosis inducton by S. lomemtaria, we examined the changes of Bcl-2 and Bax expression. The extract reduced Bcl-2, an anti-apoptotic protein, but increased Bax, a pro-apoptotic protein in a dose-dependent manner. When we examined the activation of caspase-3, an effector of apoptosis, the expression of active form(19 kDa) of caspase-3 was increased and the increase of their activities was demonstrated by the cleavage of poly(ADP-ribose)polymerase, a substrate of caspase-3, to 85 kDa. The results indicate that extract of S. lomentaria induces the apoptosis of HL-60 cells via the down-regulation of Bc1-2 and the activation of caspases.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.82-82
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• 2003

The present study was undertaken to examine the cytotoxic effect of extract of Eurya emarginata against cancer cells and to develop an anti-cancer agent using components of its leaves. The crude extract of its leaves markedly inhibited the growth of leukemia cells including HL-60. When the HL-60 cells were treated with the extract, DNA fragmentation, morphologic changes and sub-Gl hypodiploid cells were observed. Therefore, the inhibitory effect of E. emarginata on the growth of the HL-60 cells appears to arise from the induction of apoptosis. Moreover, the extract markedly reduced c-Myc expression in a time-dependent manner. Eutigoside C showing the cytotoxic effect was isolated from the leaves of E. emarginata. Eutigoside C reduced the Bcl-2 protein and mRNA levels in a time-dependent manner, whereas the Bax protein and mRNA expression levels were slightly increased. When HL-60 cells were treated with eutigoside C, the release of cytochrome C from mitochondria into the cytosol was observed. Also, the expressions of the active forms of caspase 9 and 3 were increased and the activation of caspase 3 was demonstrated by the cleavage of Poly(ADP-ribose) polymerase, a vital substrate of effector caspase. The results indicate that the eutigoside C from E. emarginata induce apoptosis of HL-60 cells via the down-regulation of Bcl-2 expression and activation of caspases.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.23 no.1
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• pp.1-14
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• 2020

The latest definition of a prebiotic is "a substrate that is selectively utilized by host microorganisms conferring a health benefit"; it now includes non-food elements and is applicable to extra-intestinal tissues. Prebiotics are recognized as a promising tool in the promotion of general health and in the prevention and treatment of numerous juvenile diseases. Prebiotics are considered an immunoactive agent, with the potential for long-lasting effects extending past active administration of the prebiotic. Because of its extremely low risk of serious adverse effects, ease of administration, and strong potential for influencing the composition and function of the microbiota in the gut and beyond, the beneficial clinical applications of prebiotics are expanding. Prebiotics are the third largest component of human breast milk. Preparations including galactooligosaccharides (GOS), fructooligosaccharides (FOS), 2'-fucosyllactose, lacto-N-neo-tetraose are examples of commonly used and studied products for supplementation in baby formula. In particular, the GOS/FOS combination is the most studied. Maintaining a healthy microbiome is essential to promote homeostasis of the gut and other organs. With more than 1,000 different microbial species in the gut, it is likely more feasible to modify the gut microbiota through the use of certain prebiotic mixtures rather than supplementing with a particular probiotic strain. In this review, we discuss the latest clinical evidence regarding prebiotics and its role in gut immunity, allergy, infections, inflammation, and functional gastrointestinal disorders.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.4
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• pp.1807-1810
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• 2014

Background: It is known that inducible nitric oxide synthase (iNOS)/nitric oxide (NO) plays an integral role during intestinal inflammation, an important factor for colon cancer development. Natural compounds from Curcuma longa L. (Zingiberaceae) have long been a potential source of bioactive materials with various beneficial biological functions. Among them, a major active curcuminoid, demethoxycurcumin (DMC) has been shown to possess anti-inflammatory properties in lipopolysaccharide (LPS)-activated macrophages or microglia cells. However, the role of DMC on iNOS expression and NO production in an in vitro inflamed human intestinal mucosa model has not yet been elucidated. This study concerned inhibitory effects on iNOS expression and NO production of DMC in inflamed human intestinal Caco-2 cells. An in vitro model was generated and inhibitory effects on NO production of DMC at 65 ${\mu}M$ for 24-96 h were assessed by monitoring nitrite levels. Expression of iNOS mRNA and protein was also investigated. DMC significantly decreased NO secretion by 35-41% in our inflamed cell model. Decrease in NO production by DMC was concomitant with down-regulation of iNOS at mRNA and protein levels compared to proinflammatory cytokine cocktail and LPS-treated controls. Mechanism of action of DMC may be partly due to its potent inhibition of the iNOS pathway. Our findings suggest that DMC may have potential as a therapeutic agent against inflammation-related diseases, especially in the gut.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6549-6556
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• 2013

Leukemia stem cells (LSCs) play important roles in leukemia initiation, progression and relapse, and thus represent a critical target for therapeutic intervention. Hence, it is extremely urgent to explore new therapeutic strategies directly targeting LSCs for acute myelogenous leukemia (AML) therapy. We show here that Angelica sinensis polysaccharide (ASP), a major active component in Dong quai (Chinese Angelica sinensis), effectively inhibited human AML $CD34^+CD38^-$ cell proliferation in vitro culture in a dose-dependent manner while sparing normal hematopoietic stem and progenitor cells at physiologically achievable concentrations. Furthermore, ASP exerted cytotoxic effects on AML K562 cells, especially LSC-enriched $CD34^+CD38^-$ cells. Colony formation assays further showed that ASP significantly suppressed the formation of colonies derived from AML $CD34^+CD38^-$ cells but not those from normal $CD34^+CD38^-$ cells. Examination of the underlying mechanisms revealed that ASP induced $CD34^+CD38^-$ cell senescence, which was strongly associated with a series of characteristic events, including up-regulation of p53, p16, p21, and Rb genes and changes of related cell cycle regulation proteins P16, P21, cyclin E and CDK4, telomere end attrition as well as repression of telomerase activity. On the basis of these findings, we propose that ASP represents a potentially important agent for leukemia stem cell-targeted therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6761-6767
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• 2013

The nuclear receptor, peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$), is expressed in various cancer cells including breast, prostate, colorectal and cervical examples. An endogenous ligand of $PPAR{\gamma}$, 15-deoxy-${\Delta}^{12,14}$ prostaglandin $J_2$ (PGJ2), is emerging as a potent anticancer agent but the exact mechanism has not been fully elucidated, especially in breast cancer. The present study compared the anticancer effects of PGJ2 on estrogen receptor alpha ($ER{\alpha}$)-positive (MCF-7) and $ER{\alpha}$-negative (MDA-MB-231) human breast cancer cells. Based on the reported signalling cross-talk between $ER{\alpha}$ and $ER{\alpha}$, the effect of the $ER{\alpha}$ ligand, $17{\beta}$-estradiol (E2) on the anticancer activities of PGJ2 in both types of cells was also explored. Here we report that PGJ2 inhibited proliferation of both MCF-7 and MDA-MB-231 cells by inducing apoptotic cell death with active involvement of mitochondria. The presence of E2 potentiated PGJ2-induced apoptosis in MCF-7, but not in MDA-MB-231 cells. The $ER{\alpha}$ antagonist, GW9662, failed to block PGJ2-induced activities but potentiated its effects in MCF-7 cells, instead. Interestingly, GW9662 also proved capable of inducing apoptotic cell death. It can be concluded that E2 enhances $ER{\alpha}$-independent anticancer effects of PGJ2 in the presence of its receptor.

• Journal of the Institute of Electronics and Information Engineers
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• v.50 no.12
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• pp.98-106
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• 2013

The duty-cycle synchronization among mobile sensor nodes with energy-harvesting is very important. The nodes should keep their duty-cycle same to others as much as possible because they have to cooperate each other and to consume energy efficiently. The distribution of node position in network affects not only node connectivity but also the active time of synchronized nodes, and it relates to network life-time finally. In this paper, we introduce a network topology change algorithm (TCA) for energy-harvesting mobile sensor networks based on self-synchronized duty-cycling. The algorithm tries to change a network topology into a balanced topology where the mobile sensor nodes are unified according to the density of the number of nodes. For TCA, both fluid flow algorithm and flock dispersion algorithm are proposed and they are evaluated through the simulation in agent based modeling language. TCA is applied to the energy-harvesting mobile sensor networks to improve the synchronization of duty-cycle and to reduce the variation of energy consumption among nodes.

• Archives of Pharmacal Research
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• v.26 no.4
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• pp.264-269
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• 2003

5-Aminosalicylic acid (5-ASA) is an active ingredient of therapeutic agents used for Crohn s disease and ulcerative colitis. Because it is absorbed rapidly and extensively in the upper intestine, delivery of the agent specifically to the colon is necessary. We selected taurine as a colon-specific promoiety and designed 5-aminosalicyltaurine (5-ASA-Tau) as a new colon-specific prodrug of 5-aminosalicylic acid (5-ASA). It was expected that introduction of taurine would restrict the absorption of the prodrug and show additive effect to the anti-inflammatory action of 5-ASA after hydrolysis. 5-ASA-Tau was prepared in good yield by a simple synthetic route. The apparent partition coefficient of 5-ASA-Tau in 1-octanol/pH 6.8 phosphate buffer or $CHCl_3$/pH 6.8 phosphate buffer was 0.10 or 0.18, respectively, at $37^{\circ}C$. To determine the chemical and biochemical stability in the upper intestinal environment, 5-ASA-Tau was incubated in pH 1.2 and 6.8 buffer solutions, and with the homogenates of tissue and contents of stomach or small intestine of rats at $37^{\circ}C$. 5-ASA was not detected from any of the incubation medium with no change in the concentration of 5-ASA-Tau. On incubation of 5-ASA-Tau with the cecal and colonic contents of rats, the fraction of the dose released as 5-ASA was 45% and 20%, respectively, in 8 h. Considering low partition coefficient and stability in the upper intestine, 5-ASA-Tau might be nonabsorbable and stable in the upper intestine. After oral administration, it would be delivered to the colon in intact form and release 5-ASA and taurine. These results suggested 5-ASA-Tau as a promising colon-specific prodrug of 5-ASA.

• Molecular & Cellular Toxicology
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• v.5 no.3
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• pp.257-264
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• 2009

Gardenia yellow, extracted from gardenia fruit, has been widely used as a coloring agent for foods, and thus, safety of its usage is of prime importance. In the current study, short-term genotoxicity assays were conducted to evaluate the potential genotoxic effects of gardenia yellow. The gardenia yellow used was found to contain 0.057 mg/g of genipin, a known biologically active compound of the gardenia fruit extract. Ames test did not reveal any positive results. No clastogenicity was detected by a chromosomal aberration test, even on evaluation at the highest feasible concentration of gardenia yellow. Gardenia yellow was also shown to be non-genotoxic using an in vitro comet assay and a micronucleus test with L5178Y cells, although a marginal increase in DNA damage and micronuclei frequency was reported in the respective assays. Additionally, in vivo micronucleus test results clearly demonstrated that oral administration of gardenia yellow did not induce micronuclei formation in the bone marrow cells of male ICR mice. Taken together, our results indicate that gardenia yellow is not mutagenic to bacterial cells, and that it does not cause chromosomal damage in mammalian cells, either in vitro or in vivo.

• Tribology and Lubricants
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• v.31 no.3
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• pp.79-85
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• 2015

RC delay is a critical issue for achieving high performance of ULSI devices. In order to minimize the RC delay time, we uses the CMP process to introduce high-conductivity Cu and low-k materials on the damascene. The low-k materials are generally soft and fragile, resulting in structure collapse during the conventional high-pressure CMP process. One troubleshooting method is electrochemical mechanical polishing (ECMP) which has the advantages of high removal rate, and low polishing pressure, resulting in a well-polished surface because of high removal rate, low polishing pressure, and well-polished surface, due to the electrochemical acceleration of the copper dissolution. This study analyzes an electrochemical state (active, passive, transpassive state) on a potentiodynamic curve using a three-electrode cell consisting of a working electrode (WE), counter electrode (CE), and reference electrode (RE) in a potentiostat to verify an electrochemical removal mechanism. This study also tries to find optimum conditions for ECMP through experimentation. Furthermore, during the low-pressure ECMP process, we investigate the effect of current density on surface roughness and removal rate through anodic oxidation, dissolution, and reaction with a chelating agent. In addition, according to the Faraday’s law, as the current density increases, the amount of oxidized and dissolved copper increases. Finally, we confirm that the surface roughness improves with polishing time, and the current decreases in this process.