• Archives of Pharmacal Research
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• v.27 no.7
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• pp.683-692
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• 2004

Curcumin (diferuloylmethane) is a major naturally-occurring polyphenol of Curcuma species, which is commonly used as a yellow coloring and flavoring agent in foods. Curcumin has shown anti-carcinogenic activity in animal models. Curcumin possesses anti-inflammatory activity and is a potent inhibitor of reactive oxygen-generating enzymes such as lipoxygenase/cyclooxygenase, xanthine dehydrogenase/oxidase and inducible nitric oxide synthase; and an effective inducer of heme oxygenase-1. Curcumin is also a potent inhibitor of protein kinase C(PKC), EGF(Epidermal growth factor)-receptor tyrosine kinase and LĸB kinase. Subsequently, curcumin inhibits the activation of NF(nucleor factor)KB and the expressions of oncogenes including c-jun, c-fos, c-myc, NIK, MAPKs, ERK, ELK, PI3K, Akt, CDKs and iNOS. It is proposed that curcumin may suppress tumor promotion through blocking signal transduction path-ways in the target cells. The oxidant tumor promoter TPA activates PKC by reacting with zinc thiolates present within the regulatory domain, while the oxidized form of cancer chemopreventive agent such as curcumin can inactivate PKC by oxidizing the vicinal thiols present within the catalytic domain. Recent studies indicated that proteasome-mediated degradation of cell proteins playa pivotal role in the regulation of several basic cellular processes including differentiation, proliferation, cell cycling, and apoptosis. It has been demonstrated that curcumin-induced apoptosis is mediated through the impairment of ubiquitin-proteasome pathway. Curcumin was first biotransformed to dihydrocurcumin and tetrahydrocurcumin and that these compounds subsequently were converted to monoglucuronide conjugates. These results suggest that curcumin-glucuronide, dihydrocurcumin-glucuronide, tetrahydrocurcumin-glucuronide and tetrahydrocurcumin are the major metabolites of curcumin in mice, rats and humans.

• International Journal of Oral Biology
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• v.41 no.2
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• pp.69-74
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• 2016

Skin-derived precursors (SKPs) have potential to differentiate to various cell types including osteoblasts, adipocytes and neurons. SKPs are a candidate for cell-based therapy since they are easily accessible and have multipotency. Most mammalian cells are exposed to a low oxygen environment with 1 to 5% $O_2$ concentration in vivo, while 21% $O_2$ concentration is common in in vitro culture. The difference between in vitro and in vivo $O_2$ concentration may affect to the behavior of cultured cells. In this report, we investigated the effect of hypoxic condition on stemness and proliferation of SKPs. The results indicated that SKPs exposed to hypoxic condition for 5 days showed no change in proliferation. In terms of mRNA expression, hypoxia maintained expression of stemness markers; whereas, oncogenes, such as Klf4 and c-Myc, were downregulated, and the expression of Nestin, related to cancer migration, was also downregulated. Thus, SKPs cultured in hypoxia may reduce the risk of cancer in SKP cell-based therapy.

• Proceedings of the Korean Society of Developmental Biology Conference
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• 1998.07a
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• pp.32-33
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• 1998

생물체에서 유전외적 변형의 하나인 DNA 메틸화는 cis-acting factor의 조성변화를 통하여 세포특이 유전자의 발현과 virus latency, genomic imprinting, mutagenesis등과 같은 생물학적 효과를 나타내는 것으로 알려져 있다.(reviewed by Olle Heby, 1995). 5-azaCR, 5-azaCdR 그리고 6-azaCR의 처리결과는 배아자체의 DNA 메틸화의 유지가 정상발생에 필수적임을 알 수 있으며, 메틸화에 의한 배아발생 조절기작이 존재함을 암시하고 있다. 이러한 과정에서 5-azaCR과 5-azaCdR은 서로다른 경로를 통하여 배아발생에 관여함을 보여주었다. 즉, 5-azaCdR은 주로 DNA에 incorporation되어 작용하는 것으로 여겨지며, 5-azaCR은 DNA 보다는 RNA에 incorporation되어 작용하는 것으로 나타났다. 그리고, 비록 소수의 유전자만이 조사되었지만, 5-azaCdR의 incorporation에 의한 cis-acting factor의 변화는 전사인자인 c-myc proto-oncogene과 fluid 수송에 관여하는 $Na^{+}$, $K^{+}$-ATPase 유전자의 전사를 억제하지 않았다. 반면, 5-azaCR의 RNA로의 incorporation은 전사인자인 c-myc proto-oncogene의 전사를 억제하였으며, 연이어 fluid 수송에 관련되어있는 $Na^{+}$, $K^{+}$-ATPase 유전자의 전사를 억제하였다. 이것은 아마도 RNA로 incorporation된 5-azaCR은 RNA의 post-transcriptional processing에 영향을 주어 trans-acting factor의 조성을 변화, 전사적 repression을 유발한 것으로 사료된다. 생쥐 착상전 초기배아에서 DNA 메틸화는 short-term하게는 cis-acting factor로써 전사적 수준에서 유전자발현 조절하며, 그리고 유전자발현을 통하여 long-term하게는 배아발생에 관여 할 것이라고 사료된다.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.22 no.1
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• pp.11-32
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• 2009

Objective : This study was designed to investigate anti-cancer and whitening activities (LC). So it was investigated the effects of LC on proliferation rates of melanoma genetic profile by LC. Methods : The genetic profile for the effect of LC on human derived melanoma cell, SK-MEL-2, was measured using microarray technique, and the functional analysis on these genes were conducted. Total 441 genes were up-regulated and 830 genes down-regulated in cells treated with LC. Genes induced or suppressed by LC were all mainly concerned with basic signalling pathways, which are involved in cell growth, differentiation and migration. Especially, many genes, which are related in apoptosis and cell cycle arrest were up-regulated by treatment with LC, and genes related in cell cycle were down-regulated. Result : The network of total protein interactions were identified by using cytoscape program, and some key molecules, such as BCL2L1, SIN3A, SMAD2 and c-myc that can be used for elucidation of therapeutical mechanism of medicine in the future. Conclusion : These results suggest possibility of LC as addition drug and whitening cosmetics. In addition, it was also suggested that related mechanisms are involved in BCL2L1, SIN3A, SMAD2 and c-myc related signalling pathways.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.11a
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• pp.17-20
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• 1993

As a step toward a more complete understanding of the molecular actions of TNF, we prepared a cDNA library from TNF-treated human FS-4 fibroblasts and used differential hybridization to identify cDNA clones corresponding to mRNAs enriched in TNF-treated eells. In Quiescent FS-4 cells n induces an increase in the level of some mRNAs within 20 to 30 min. Some of these immediate-early response mRNAs are elevated only transiently for about 30 to 120 min, e. g., c-fos and c-myc (Lin and Vilcek,1987) or the transcription factor IRF-1 (Fujita et al.1989). Such immediate-early gene products may be important for the activation of other genes, but their transient induction suggests that they are not the actual effector molecules responsible for the phenotypic changes induced by TNF. We chose a 3-h incubation with W because we were seeking cDNAs corresponding to messages that are more stably elevated after TNF treatment. Indeed, the results shown in Figure 8 and 9 indicate that all of the mRNAs corresponding to the eight TSG cDNAs isolated remained significantly elevated after 16h of continuous treatment with TNF, and their kinetics of induction were clearly different from those of the immediate-early response mRNAs such as c-fos, c-myc or IRF-1. Nevertheless, only the induction of TSG-21 (collagenase) and TSG-27 (stromelysin) nNAs was completely inhibited by cycloheximide and the induction of TSG-37 (metallothionein-II) was reduced in the presence of this inhibitor of protein synthesis. Induction of the other five TSG mRNAs by TNF was completelyresistant to cycloheximide, suggest ins that no protein intermediate is needed for the upregulation of these mRNAs.

• Archives of Pharmacal Research
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• v.25 no.5
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• pp.561-571
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• 2002

The action mechanisms of several chemopreventive agents derived from herbal medicine and edible plants have become attractive issues in cancer research. Tea is the most widely consumed beverage worldwide. Recently, the cancer chemopreventive actions of tea have been intensively investigated. It have been demonstrated that the active principles of tea were attributed to their tea polyphenols. Recently, tremendous progress has been made in elucidating the molecular mechanisms of cancer chemoprevention by tea and tea polyphenols. The suppression of various tumor biomarkers including growth factor receptor tyrosine kinases, cytokine receptor kinases, P13K, phosphatases, ras, raf, MAPK cascades, NㆍFB, IㆍB kinase, PKA, PKB, PKC, c-jun, c-fos, c-myc, cdks, cyclins, and related transducing proteins by tea polyphenols has been studied in our laboratory and others. The IㆍB kinase (IKK) activity in LPS-activated murine macrophages (RAW 264.7 cells) was found to be inhibited by various tea polyphenols including (-) epigallocatechin-3-gallate (EGCG), theaflavin (TF-1), theaflavin-3-gal-late (TF-2) and theaflavin-3,3'-digallate (TF-3). TF-3 inhibited IKK activity in activated macrophages more strongly than did the other tea polyphenols. TF-3 inhibited both IKK1 and IKK2 activity and prevented the degradation of IㆍBㆍand IㆍBㆍin activated macrophage cells. The results suggested that the inhibition of IKK activity by TF-3 and other tea polyphenols could occur by a direct effect on IKKs or on upstream events in the signal transduction pathway. TF-3 and other tea polyphenols blocked phosphorylation of IB from the cytosolic fraction, inhibited NFB activity and inhibited increases in inducible nitric oxide synthase levels in activated macrophage. TF-3 and other tea polyphenols also inhibited strongly the activities of xanthine oxidase, cyclooxygenase, EGF-receptor tyrosine kinase and protein kinase C. These results suggest that TF-3 and other tea polyphenols may exert their cancer chemoprevention through suppressing tumor promotion and inflammation by blocking signal transduction. The mechanisms of this inhibition may be due to the blockade of the mitogenic and differentiating signals through modulating EGFR function, MAPK cascades, NFkB activation as wll as c-myc, c-jun and c-fos expression.

• Journal of Life Science
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• v.33 no.11
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• pp.868-875
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• 2023

Kinesin-1 is a motor protein identified as the first member of the kinesin superfamily (KIF), which plays a role in intracellular cargo transport by acting as microtubule-dependent motor proteins within cells. Kinesin-1 consists of two heavy chains (KHCs, also known as KIF5s) and two light chains (KLCs). The 93 amino acids in the carboxyl (C)-terminal tail region of KIF5A are not homologous to the C-terminal tail region of KIF5B or the C-terminal tail region of KIF5C. In this study, we used a yeast two-hybrid screen to identify the binding proteins that interacted with the C-terminal region of KIF5A. We found an association between KIF5A and CUE domain containing 2 (CUEDC2), which is proposed to function as an adaptor protein involved in ubiquitination pathways and protein trafficking. CUEDC2 bound to the C-terminal region of KIF5A and did not interact with KIF5B (the motor of kinesin-1), KIF3A (the motor of kinesin-2), or kinesin light chain 1 (KLC1). KIF5A specifically bound to the C-terminal region of CUEDC2. Furthermore, KIF5A did not interact with another isoform: CUEDC1. In addition, glutathione S-transferase (GST) pull-downs showed that KIF5A directly bound GST-CUEDC2 but did not interact with GST-CUEDC1 and GST alone. When myc-KIF5A and EGFP-CUEDC2 were co-expressed in HEK-293T cells, CUEDC2 co-immunoprecipitated with kinesin-1, and myc-KIF5A and FLAG-CUEDC2 colocalized in the cells. These results suggest that in intracellular cargo transport by kinesin-1, CUEDC2 serves as an adaptor protein connecting kinesin-1 and cargo by binding to KIF5A.

• Nutrition Research and Practice
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• v.13 no.1
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• pp.58-63
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• 2019

BACKGROUND/OBJECTIVES: Telomeres are located at the chromosomal ends and progressively shortened during each cell cycle. Telomerase, which is regulated by hTERT and c-MYC, maintains telomeric DNA sequences. Especially, telomerase is active in cancer and stem cells to maintain telomere length for replicative immortality. Recently we reported that walnut phenolic extract (WPE) can reduce cell viability in a colon cancer stem cell (CSC) model. We, therefore, investigated the effect of WPE on telomere maintenance in the same model. MATERIALS AND METHODS: $CD133^+CD44^+$ cells from HCT116, a human colon cancer cell line, were sorted by Fluorescence-activated cell sorting (FACS) and treated with WPE at the concentrations of 0, 10, 20, and $40{\mu}g/mL$ for 6 days. Telomere lengths were assessed by quantitative real-time PCR (qRT-PCR) using telomere specific primers and DNA extracted from the cells, which was further adjusted with single-copy gene and reference DNA ($ddC_t$). Telomerase activity was also measured by qRT-PCR after incubating the PCR mixture with cell protein extracts, which was adjusted with reference DNA ($dC_t$). Transcriptions of hTERT and c-MYC were determined using conventional RT-PCR. RESULTS: Telomere length of WPE-treated cells was significantly decreased in a dose-dependent manner ($5.16{\pm}0.13$ at $0{\mu}g/mL$, $4.79{\pm}0.12$ at $10{\mu}g/mL$, $3.24{\pm}0.08$ at $20{\mu}g/mL$ and $3.99{\pm}0.09$ at $40{\mu}g/mL$; P = 0.0276). Telomerase activities concurrently decreased with telomere length ($1.47{\pm}0.04$, $1.09{\pm}0.01$, $0.76{\pm}0.08$, and $0.88{\pm}0.06$; P = 0.0067). There was a positive correlation between telomere length and telomerase activity (r = 0.9090; P < 0.0001). Transcriptions of both hTERT and c-MYC were also significantly decreased in the same manner. CONCLUSION: In the present cell culture model, WPE reduced telomere maintenance, which may provide a mechanistic link to the effect of walnuts on the viability of colon CSCs.

• The Journal of Korean Obstetrics and Gynecology
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• v.23 no.2
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• pp.71-84
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• 2010

Purpose: In the theory of traditional medicine, Glenditsia spina(GS) can resolve carbuncle, relive swelling, dispel wind and destroy parasites. This study was designed to investigate the effects of GS on gene expression of ovarian tissue in polycystic ovary syndrome(PCOS) rats. Methods: In this experiment, female rats injected with a single dose of 2 mg estradiol valerate(EV) and GS was given for 5 weeks. The genetic profile for the effects on ovarian tissue in PCOS rats was measured using microarray technique, and the functional analysis on these genes was conducted. Results: 985 genes were increased in control and restored to normal level in GS group. (B), 733 genes were decreased in control group and restored to normal level in GS group. (F). Metabolic pathways related in B group genes were Graft-versus-host disease, Allograft rejection, Autoimmune thyroid disease, Cytokine-cytokine receptor interaction, Small cell lung cancer, Type I diabetes mellitus. Metabolic pathways related in F group genes were Antigen processing and present, Adipocytokine signalling pathway, Focal adhesion, ECM-receptor interaction, Pancreatic cancer, Notch signalling pathway, Tight junction. The network of total protein interactions was measured using cytoscape program, and some key molecules, such as c-Fos, c-Myc, ABL1 related in B group, MAPK8, RASA1, CALR related in F group that can be used for elucidation of therapeutical mechanism of medicine in future were identified. Conclusion: These results suggest possibility of GS as anti-cancer and anti-hyperplasia drug in PCOS. In addition, the present author also suggests that related mechanisms are involved in suppression of proto-oncogene such as c-Fos, c-Myc and ABL1, and in regulation of cell cycle such as RASA1.

• Journal of Life Science
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• v.9 no.3
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• pp.268-275
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• 1999

Rhodopseudomonas sp. was immobilized in three supports(agar, k-carrageenan, and PVA) in order to remove nitrate in wastewater coming from fish farm. Among them 3% agar was the most suitable support when denitrification rate and bead durability were tested. Optimum bead size was 4mm-diameter when the substrate transfer into the bead and shear stress for bead were considered, and optimum cell loading was 25mg dry $cells/cm^2$gel gel. Ethanol was the best as a carbon source, and optimum C:N ratio, temperature and pH were 1.5:1, $31^{\circ}C$,, and 6, respectively. Under these conditions the maximum denitrification rate in synthetic wastewater was $$345{\MU}{\ell};N_2/Cm^3 gel{\cdot}hr;and that in modified MYC medium was 450{\MU}{\ell}};N_2/Cm^3 gel{\cdot}hr $$.