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Molecular Mechanisms of Cell Cycle Arrest and Apoptosis by Dideoxypetrosynol A, a Polyacetylene from the Sponge Petrosia sp., in Human Monocytic Leukemia Cells

  • Choi, Yung Hyun
    • Journal of Marine Bioscience and Biotechnology
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    • v.1 no.4
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    • pp.243-251
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    • 2006
  • Dideoxypetrosynol A, a polyacetylene from the marine sponge Petrosia sp., is known to exhibit significant selective cytotoxic activity against a small panel of human tumor cell lines, however, the mechanisms of which are poorly understood. In the present study, it was investigated the further possible mechanisms by which dideoxytetrosynol A exerts its anti-proliferative action in cultured human leukemia cell line U937. We observed that the proliferation-inhibitory effect of dideoxypetrosynol A was due to the induction of G1 arrest of the cell cycle and apoptosis, which effects were associated with up-regulation of cyclin D1 and down-regulation of cyclin E without any change in cyclin-dependent-kinases (Cdks) expression. Dideoxypetrosynol A markedly induced the levels of Cdk inhibitor p16/INK4a expression. Furthermore, down-regulation of phosphorylation of retinoblastoma protein (pRB) by this compound was associated with enhanced binding of pRB and the transcription factor E2F-1. The increase in apoptosis was associated with a dose-dependent up-regulation in pro-apoptotic Bax expression and activation of caspase-3 and caspase-9. Dideoxytetrosynol A decreased the levels of cyclooxygenase (COX)-2 mRNA and protein expression without significant changes in the levels of COX-1, which was correlated with a decrease in prostaglandin E2 (PGE2) synthesis. Furthermore, dideoxytetrosynol A treatment markedly inhibited the activity of telomerase, and the expression of human telomerase reverse transcriptase (hTERT), a main determinant of the telomerase enzymatic activity, was progressively down-regulated by dideoxytetrosynol A treatment in a dose-dependent fashion. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of dideoxytetrosynol A.

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Induction of S Phase Arrest of the Cell Cycle by Piceatannol is Associated with Inhibition of Telomerase Activity in Human Leukemic U937 Cells (Piceatannol에 의한 인체 혈구암세포의 증식 억제 및 telomerase 활성 저하)

  • Choi, Yung-Hyun
    • Journal of Life Science
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    • v.18 no.1
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    • pp.96-102
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    • 2008
  • Piceatannol is a polyphenol that is found in abundant quantities in grapes and wine. Although recent experimental data revealed the anti-cancer potency of piceatannol, the molecular mechanisms underlying the antileukemic activity have not yet been studied in detail. In the present study, we investigated further possible mechanisms by which piceatannol exerts its anti-proliferative action in cultured human leukemia U937 cells. Exposure of U937 cells to piceatannol resulted in growth inhibition and induction of apoptosis as measured by MTT assay and flow cytometry analysis, which was associated with S phase arrest of the cell cycle. Piceatannol treatment markedly inhibited the activity of telomerase, and the levels of human telomerase reverse transcriptase (hTERT) and telomerase-associated protein-1 (TEP-1), main determinants of the telomerase enzymatic activity, were progressively down-regulated by piceatannol treatment in a dose-dependent fashion. However, the levels of cyclooxygenases (COXs) expression and prostaglandin E2 (PGE2) release were not changed in piceatannol-treated U937 cells. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of piceatannol.

The Study on the History of Pugation therapy From -'Treatise on Febrile Diseases' to 'Longevity and Life Presservation In Oriental Medicine'- (하법(下法)의 발전 과정에 대한 연구(硏究) -상한론(傷寒論)에서 사상의학(四象醫學) 까지-)

  • Choi, Yei-Kwen;Kim, Kyung-Yo
    • The Journal of Internal Korean Medicine
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    • v.19 no.1
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    • pp.524-552
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    • 1998
  • Purgation therapy has played an important role as a influential remedy from the begining of the Chinese medicine. Especially purgation therapy is raised as the effective remedy on the acute infectious disease in the book of 'Treatise on Febrile Disease'. But It was inclined to cold-nature and available only in the excess syndrome. Nevertheless it is evident that the book has showed an example of this therapy. During the middle age, purgation therapy is classified into several subtype; hydrogogue therapy, laxation with lubricants, purgation with cold-natured drugs and purgation with warm-natured drugs. Comparing with the ancient times, it must be a progression. It was investigated earnestly by a school leaded by Zhang Congzheng. They were not restricted to several diseases, but applied it to the wide range of diseases. They thought as following. 'One is ill from pathogenic factor so that you should eliminate it from the human body'. Hence, they frequently used three major remedies such as diaphoresis, emesis and purgation. In this process, purgation therapy had showed eye-opening progress. But opposition to it was not little. Li Gao was a representative man on the opposite side. He expressed a critical opinion and placed great importance on the genuine energy, the natural healing force. Under his influence, a large number of doctors evaded purgation and put it under taboo. On account of these trend, purgation therapy had took a backward step and retrograded. Therefore cathartics such as Rhei Radix et Rhizoma, Rharbitidis Semen, cold drugs such as Gypsum Fibrosum, etc. had been excluded for preservation of the genuine energy, and came about an obnoxious custom to value only 'tonity deficiency', or 'warm and tonify'. As it had came into fashion to approach most disease from the point of view, purgation therapy was merely fall into a remedy of constipation. After the eighteenth century purgation therapy encountered the new period of rivival. It was introduced by them who strived for the study of Epidemics to the new current of thought, so called '增水行舟'. It was because 온병 was apt to dissipate one's Yin fluid. Therefore purgation therapy of this period was characterized by establishing nourishment Yin and body fluid with or without use of timely purgation of accumulation of heat. From the time of Zhang Congzheng, it was accomplished by Lee Je-ma to the most epoch-making change. He caused an improvement in the use of purgation therapy by regarding innate constitutional contradiction as importance than representing clinical symptoms. He warned that existing remedies that depend only upon symptoms and signs, not upon individual characteristics including constitutional features didn't bring round to but kill them. And he understood all the pathologic processes in his constitutional theory, investigated specific drugs on four constitution, made indications of each prescriptions clear. For giving to differentiation of constition before differentiation of syndrom, his new slant on the pathologic phenomena overcome the limitations of 변증시치, and revaluate purgation therapy from remedy impaire the genuine energy to that restore it by recover the balance between the internal organ. It is the product of him to fundamentally upset the cause to be in disregard of purgation therapy.

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Glutamine Deprivation Inhibits Invasion of Human Prostate Carcinoma LnCap Cells through Inactivation of Matrix Metalloproteinases and Modulation of Tight Junctions (글루타민 결핍에 따른 Tight Junction 및 MMPs 활성 조절을 통한 전립선 암세포의 침윤 억제 현상)

  • Shin, Dong Yeok;Choi, Yung Hyun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.42 no.8
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    • pp.1167-1174
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    • 2013
  • Cancer cells exhibit increased demand for glutamine-derived carbons to support anabolic processes. Indeed, the spectrum of glutamine-dependent tumors and the mechanisms through which glutamine supports cancer metabolism remain areas of active investigation. In the present study, we investigated the effects of glutamine deprivation on the correlation between tightening of tight junctions (TJs) and anti-invasive activity in human prostate carcinoma LnCap cells. Glutamine deprivation markedly inhibited cell motility and invasiveness in a time-dependent manner. The anti-invasive activity of glutamine deprivation was associated with an increased tightness of the TJ, which was demonstrated by an increase in transepithelial electrical resistance (TER). The activities of matrix metalloproteinase (MMP)-2 and MMP-9 were inhibited in a time-dependent fashion by glutamine deprivation, which was correlated with a decrease in expression of their mRNA and proteins and up-regulation of tissue inhibitors of metalloproteinases (TIMPs) expression. Furthermore, glutamine deprivation repressed the levels of the claudin family members, which are major components of TJs that play a key role in the control and selectivity of paracellular transport. Moreover, the levels of E-cadherin, a type I transmembrane glycoprotein, and snail, an epithelial to mesenchymal transition regulator and zinc finger transcription factor, were markedly modulated by glutamine deprivation. Taken together, these findings suggest that TJs and MMPs are critical targets of glutamine deprivation-induced anti-invasion in human prostate carcinoma LnCap cells.

Study on the Surface Design Used in S.F.A.A. Collection (SFAA 컬렉션에 활용된 서페이스 디자인연구)

  • 김주희;금기숙
    • Journal of the Korean Society of Costume
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    • v.52 no.1
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    • pp.129-143
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    • 2002
  • Patterns are something that comes out of necessity in human life, which is closely associated with it. Thus come the SFAA (Seoul Fashion Artists Association) collection which uses patterns varying in form, color, way of expression and material. For this research, I first categorized the patterns the SFAA designers used into: natural patterns, symmetric patterns, traditional patterns, stripe, plaid, dot and abstract patterns. As a result of the process. the designers most favored the natural patterns and symmetric patterns, and dot patterns were rarely used. The designer who most favored patterns in general was Sul Yun-hyoung, and the designer Kim Chul-ung rarely favored the surface effect. The seven kinds of patterns naturally differ according to the designer. as Park Hang-chi liked to use the plaid patterns along with yam dyeing material, whereas Jin Teok expressed stripe patterns using the yarn dyeing fabric. Natural patters were presented in a bizarre way with Lie Sang-bong. who took the motives appearing in Eastern ceramic and paintings into the clothes, using the print method. The symmetric patterns, which the SFAA designers most preferred. was used evenly among designers like Chang Kwang-hyo, Gee Choon-hee. Rubina, and Haneza. In contrast. Lie Sang-bong. who used abstract patterns that do not give out meaning of the actual form of the pattern. rarely used symmetric patterns. The dot patterns were most often used by Park Youn-soo. and traditional patterns were overwhelmingly chosen by Sul Yun-hyoung. Secondly. in expressing the colors, SFAA designers were much more likely to choose achromatic colors. not choosing to show off colors. This is especially apparent in works by Haneza and Lie Sang-bong. In the SFAA collections, numerous methods were used to create. For instance, Sul Yun-hyoung used the oriental embroidery method. and Rubina and Lie Sang-bong used many unique dying methods. In terms of materials, Sul Yun-hyoung preferred silk. due to her methods, and Lie Sang-bong was one of the designers that used a number of different materials such as vinyl. Jacques Mueclier of the Paris Clothes Association in France, who was invited to SFAA collection once, remarked. "While the choice of material and the actual sewing done were excellent, there lacked much difference among the designers, as most of them choose flowing silhouette In terms of composition," which is all too correct. In addition, there were cases in the collection where the inherent feelings of cultural artifacts was expressed without alteration. Summing up, the research aimed to analyze the surface expression methods, forms and color of SFAA designs. and I hope that it can open up ways for new projects in the future.he future.