• Bulletin of the Korean Chemical Society
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• 제32권7호
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• pp.2391-2396
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• 2011

Benzonaphthofurandiones containing four coplanar fused aromatic rings were synthesized and evaluated for their cytotoxicity against five human cancer cell lines, and their inhibitory activity on topoisomerases. These benzonaphthofurandiones were prepared by condensation of 2,3-dichloronaphthoquinone and three aromatic diols with base catalysts in alcohol. The synthesized compounds were o-alkylated with six dialkylaminoalkyl halides. The hydroxy derivatives (8a-8g) exhibited relatively potent cytotoxicity among the prepared compounds. These compounds were evaluated as excellent inhibitors against topoisomerase II (topo II). Especially, the hydroxy analogue with branched methyl side chain (8e) showed high cytotoxicity against cancer cell lines and good inhibitory activity on topo II.

• 한국전산유체공학회:학술대회논문집
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• 한국전산유체공학회 2011년 춘계학술대회논문집
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• pp.46-53
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• 2011

Water is continuously produced in polymer electrolyte membrane fuel cell (PEMFC), and is transported and exhausted through polymer electrolyte membrane (PEM), catalyst layer (CL), microporous layer (MPL), and gas diffusion layer (GDL). The low operation temperatures of PEMFC lead to the condensation of water, and the condensed water hinders the transport of reactants in porous layers (MPL and GDL). Thus, water flooding is currently one of hot issues that should be solved to achieve higher performance of PEMFC. This research aims to study liquid water transport in porous layers of PEMFC by using pore-network model, while the microscale pore structure and hydrophilic/hydrophobic surface properties of GDL and MPL were fully considered.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.90.2-90.2
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• 2003

In a continuous effort to develop novel anticancer agents we newly synthesized and evaluated the antitumor activity of nucleoside analogues. One analogue, 4-[2-Chlor-6-(3-iodo-benzylamino)-purin-9-yl]-2,3-dihydroxy-cyclopentanecarboxylic acid methylamide (LJ-331), has been shown to exert a potent inhibition of human cancer cell growth in vitro including human lung (A549), stomach (SNU-638) and leukemia (HL-60) cancer cells. Following mechanism of action study revealed that LJ-331 induces cell cycle arrest at the G$_1$ phase in HL-60 cells and evokes apoptotic phenomena such as an increase in DNA ladder intensity and chromatin condensation by a dose-and time-dependent manner. (omitted)

• 한국약용작물학회지
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• 제17권2호
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• pp.145-150
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• 2009

This study investigated the protective roles and mechanism of magnolol, from the stem bark of Magnolia officinalis against potential neurotoxin 3-hydroxykynurenine (3-HK)-induced neuronal cell death. For the evaluation of protective role of magnolol, we examined cell viability, apoptotic nuclei, change of mitochondrial membrane potential and caspase activity in human neuroblastoma SH-SY5Y cells. It was found that 3-HK induces neuronal cell death in the human neuroblastoma SH-SY5Y cell line. The reduced cell viability produced characteristic features such as cell shrinkages, plasma membrane blebbing, chromatin condensation, and nuclear fragmentation. The cells treated with 3-HK showed an increase in the concentration of reactive oxygen species (ROS) as well as in caspase activity. In addition, both are involved in the 3-HK-induced apoptosis. Magnolol attenuated the cell viability reduction by 3-HK in both a dose- and time-dependent manner. Optical microscopy showed that magnolol inhibited the cell morphological features in the 3-HK-treated cells. Furthermore, the increase in the ROS concentration and the caspase activities by 3-HK were also attenuated by magnolol. These results showed that magnolol has a protective effect on the 3-HK induced cell death by inhibiting ROS production and caspase activity.

• The Korean Journal of Physiology and Pharmacology
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• 제1권6호
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• pp.699-705
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• 1997

Although it is known that neuronal cell death during development occurs by apoptosis, the mechanisms underlying excitatory amino acid-induced neuronal cell death remain poorly understood. In this study we have examined the mechanism by which L-glutamate, an excitatory amino acid neurotransmitter, induces cell death in PC12 cell lines. To characterize cell death, we employed sandwich enzyme-linked immunosorbent assay(ELISA) method for cellular DNA fragmentation, DNA agarose gel electrophoresis and chromatin staining by acridine orange and ethidium bromide after treating the PC12 cells with L-glutamate. L-Glutamate caused dose-dependent cell death with a maximum at 24 hrs after the treatment. These cellular fragmentation was blocked by pretreatment of MK-801, a noncompetitive N-methyl-D-aspartic acid(NMDA) receptor antagonist, and nerve growth factor(NGF). Analysis of DNA integrity from L-glutamate-treated cells revealed cleavage of DNA into regular sized fragments, a biochemical hallmark of apoptosis. The PC12 cells that were induced to die by L-glutamate treatment exhibited classical chromatin condensation under the light microscopy after acridine orange and ethidium bromide staining. These results suggest that apoptosis is one of the key features that are involved in L-glutamate-induced excitotoxic cell death in PC12 cells, and these cell death are mediated by NMDA receptor and depend on NGF.

• Biomolecules & Therapeutics
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• 제15권2호
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• pp.95-101
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• 2007

Resveratrol (3,5,4’-trihydroxy-trans-stilbene), a naturally occurring phytoallexin abundant in grapes and several plants, has been shown to be active in inhibiting proliferation and inducing apoptosis in several human cancer cell lines. On the line of the biological activity of resveratrol, a variety of resveratrol analogs were synthesized and evaluated for their growth inhibitory effects against several human cancer cell lines. In the present study, we found that one of the resveratrol analogs, 3,4,5-trimethoxy-4’-bromo-cis-stilbene, markedly suppressed human colon cancer cell proliferation (EC$_{50}$ = 0.01 ${\mu}$g/ml), and the inhibitory activity was superior to its corresponding trans-isomer (EC$_{50}$ = 1.6 ${\mu}$g/ml) and resveratrol (EC$_{50}$ = 18.7 ${\mu}$g/ml). Prompted by the strong growth inhibitory activity in cultured human colon cancer cells (Col2), we investigated its mechanism of action. 3,4,5-Trimethoxy-4’-bromo-cis-stilbene induced arrest of cell cycle progression at G2/M phase and increased at sub-G1 phase DNA contents of the cell cycle in a time- and dose-dependent manner. Colony formation was also inhibited in a dose-dependent manner, indicating the inhibitory activity of the compound on cell proliferation. Moreover, the morphological changes and condensation of the cellular DNA by the treatment of the compound were well correlated with the induction of apoptosis. These data suggest the potential of 3,4,5-trimethoxy-4’-bromo-cis-stilbene might serve as a cancer chemotherapeutic or chemopreventive agent by virtue of arresting the cell cycle and inducing apoptosis for the human colon cancer cells.

• 약학회지
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• 제48권2호
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• pp.147-152
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• 2004

A wide variety of cancer chemotherapeutic agents have been shown to induce programmed cell death (PCD, APOPTOSIS) in various tumor cell lines in vitro. cis-Malonato [(4R,5R)-4,5-bis(aminomethyl)-2-isoprpopyl-1,3-dioxolane] platinum(II) (heptaplatin), which is a new drug approved by KFDA in 1999, in a novel platinum-based antitumor agent with clinical potential against stomach cancer and the 3rd generation of the cisplatin. This study was performed to know how heptaplatin and cisplatin and sunpla (mixture of heptaplatin and mannitol) affect on SK-MEL-28 cell line, and how they induce the apoptosis. At EM analysis, the morphology of the cell was changed by treatment of the cisplatin, heptaplatin and sunpla. Apoptotic body formed around plasma membrane, and chromatin condensation represented in nucleus. This phenomenon is one of the characteristic of the apoptosis. The DNA of SK-MEL-28 cell line truncated by cisplatin and sunpla treatment was identified on 2% agarose gel electrophoresis. TUNEL assay was performed to know whether SK-MEL-28 cell die as apoptosis or necrosis by cisplatin, heptaplatin and sunpla. At this result, fluorescence intensity increased according to increase of time and concentration. Therefore, it was identified that cislatin, heptaplatin and sunpla induced apoptosis. Fas expressed on SK-MEL-28 cell membrane by cisplatin, heptaplatin and sunpla was identified by using flow cytometer and the expression of bcl-2(anti-apoptotic gene) decreased according to increase of concentration of the cisplatin, heptaplatin and sunpla. Cisplatin, heptaplatin and sunpla induced apoptosis against SK-MEL-28 cell line, and the apoptotic mechanism was identified as Fas-mediated apoptosis and decreased bcl-2 expression.

• Restorative Dentistry and Endodontics
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• 제20권2호
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• pp.549-576
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• 1995

Bacteria are one of the most important causative agents of the pulpal and periapical diseases. Streptococci are one of the most frequently isolated facultative anarerobic bacteria in the infected root canals. Bacterial cell wall components have a direct effect in the pathogenesis of the pulpal and periapical infections. Hyaluronidase produced by bacteria has been implicated in dissemination of the diseases. The purpose of this study was to evaluate the effect of cell wall extract of streptococci on the L929 cells using inverted microscope and the transmission electron microscopy (TEM). Hyaluronidase production of streptococcal strains were investigated to determine the correlation between the severity of cell damage and the activity of enzymes. Bacterial cell wall extracts of S. sanguis, S. mitis and S. uberis isolated from infected root canals and ATCC type strains of S. mutans (ATCC 10449) and E. faecalis (ATCC 19433) were prepared by sonication and confirmed with SDS-PAGE. Silver stain of SDS-PAGE of sonic extract was efficient at $100{\mu}g$/ml concentration of cell wall protein, while Coomasie blue stain was efficient at $100{\mu}g$/ml concentration. Inverted microscope showed that sonic extract-treated L929 cells were round and detached from the substratum while others lost their fibroblastic shapes. Transmission electron microscopic examination revealed that streptococcal extracts induced death of L929 cells. Sonic extracts of streptococci had variable effect on microstructure of L929 cells. significant chromatin condensation was observed in the nucleus of the cells. Disappearance of cell surface microvilli and nuclear fragments with dense chromatin were observed. The cell nucleus had an irregular shape and numerous large vacuoles were seen in the cytoplasm and some breaks of the cell membrane could be seen. Cell organelles were in various stages of destruction and cristae of mitochondria were disoriented or disappeared. Eighteen strains of streptococci did not produce hyaluronidase.

• 한국수정란이식학회지
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• 제13권2호
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• pp.179-190
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• 1998

Prolactin (PRL) surge in cycling rats at proestrous afternoon has previously been reported as an inducer of apoptotic cell death of luteal cells. This death-inducing action of PRL seeins unusual, because PRL can he categorized as a cell-survival factor, if other known physiological functions of PRL are taken into account. In this study, the apoptotic action of PRL was assessed in cultured cells prepared from rat luteal tissue and underlying molecular /cellular mechanism of PRL-induced luteolysis was analyzed. The latest crop of corpora lutea (CLs) were enucleated from rat ovaries at 18:00 h on the proestrous day before the next ovulation. Donor rats were pretreated with CB154, a dopamine agonist, in order to he exempted from the endogenous PRL surge. The harvested GLs were dispersed and cultured with or without PRL (2$\mu$g /ml) for 24 or 48 h. An addition of PRL to the culture medium changed the parameters indicative of cell death via apoptosis: a decrease in cell viability (MTT) and an increase in chromatin condensation. Most of the DNA breakdown in nuclei induced by PRL occurred in steroidogenic cells which were identified by 3$\beta$-HSD activity staining, and the number of 3$\beta$-HSD-positivecells were significantly decreased. Interestingly, most of the cells with an apoptotic nucleus adhered to one or more intact and seemingly non-steroidogenic cells. Because the expression of Fas has heen shown to be abundant in murine ovary, and Fas is known to have an exact physiological role in occurrence of apoptotic cell death, the membrane form-Fas ligand (rnFasL) was quantified in the cell lysate. An addition of PRL increased expression of mFasL. Moreover, an addition of concanavalin A (ConA), a T-cell specific activator, in place of PRL, enhanced the apoptotic parameters. Cumulatively, the apoptotic PRL action was addressed to cells unknown than steroidogenic lute~ cells. The most prohable candidate for the direct target cells is Tcells in the luteal tissue that can express mFasL in response to PRL.

• BMB Reports
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• 제38권4호
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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.