• Journal of Life Science
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• v.23 no.5
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• pp.710-720
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• 2013

Radiotherapy is commonly used in treating many kinds of cancers which cannot be cured by other therapeutic strategies. However, radiotherapy also induces the damages on the normal tissues. Radiation-induced fibrosis is frequently observed in the patients undergoing radiotherapy, and becomes a major obstacle in the treatment of intrahepatic cancer. Hedgehog (Hh) that is an essential in the liver formation during embryogenesis is not detected in the healthy liver, but activated and modulates the repair process in damaged livers in adult. The expression of Hh increases with the degree of liver damage, regulating the proliferation of hepatic progenitors and hepatic stellate cells (HSC). In addition, Hh induces epithelial-to-mesencymal transition (EMT) and activation of myofibroblasts. In the irradiated livers, up-regulated expression of Hh signaling was associated with proliferation of progenitors, EMT induction, and increased fibrosis. Female-specific expression of Hh leaded to the expansion of progenitors and the accumulation of collagen in the irradiated livers of female mice, indicating that gender disparity in Hh expression may be related with radiation-susceptibility in female. Hence, Hh signaling becomes a novel object of studies for fibrogenesis induced by radiation. However, the absence of the established experimental animal models showing the similar physiopathology with human liver diseases and fibrosis-favorable microenvironment hamper the studies for the radiation-induced fibrosis, providing a few descriptive results. Therefore, further research on the association of Hh with radiation-induced fibrosis can identify the cell and tissue-specific effects of Hh and provides the basic knowledge for underlying mechanisms, contributing to developing therapies for preventing the radiation-induced fibrosis.

• Journal of Oral Medicine and Pain
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• v.35 no.3
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• pp.165-175
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• 2010

Valproic acid (VPA) is a well-known anticonvulsive agent and has been used in the treatment of epilepsy for almost 30 years. VPA emerged in 1997 as an antineoplastic agent as well, when findings indicated the substance inhibited proliferation and induced differentiation of primitive neuroectocdermal tumor cells in vivo (Cinatl et al., 1997). Antitmor activity of VPA is associated with its targeting histone deacetylases. Bile acids and their synthetic derivatives induced apoptosis in various kinds of cancer cells and anticancer effects. It has been reported that the synthetic chenodeoxycholic acid (CDCA) derivatives showed apoptosis-inducing activity on various cancer cells in vitro. This study was undertaken to investigate the synergistic apoptotic effect of co-treatment with the histone deacetylases inhibitor, VPA and a CDCA derivative, HS-1200 on human osteosarcoma (HOS) cells. Cell viability was evaluated by trypan-blue exclusion. Induction and augmentation of apoptosis were confirmed by Hoechst staining, flow cytometry (DNA hypoploidy and MMP change), Westen blot analysis and immunofluorescent staining. In this study, HOS cells co-treated with VPA and HS-1200 showed several lines of apoptotic manifestation such as nuclear condensations, the reduction of MMP, the decrease of DNA content, the release of cytochrome c into cytosol, the translocation of AIF onto nuclei, and activation of caspase-7, caspase-3 and PARP whereas each single treated HOS cells did not. Although the single treatment of 1 mM VPA or $25\;{\mu}M$ HS-1200 for 48 h did not induce apoptosis, the co-treatment of them induced prominently apoptosis. Therefore our data provide the possibility that combination therapy of VPA and HS-1200 could be considered as a novel therapeutic strategy for human osteosarcoma.

• Journal of Life Science
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• v.24 no.2
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• pp.137-147
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• 2014

Cortex ulmi pumilae, the cortex of Ulmus davidiana var. japonica, has been used in traditional folk medicine for its anti-inflammatory effect. Although its various bioactivities such as anti-inflammatory, anti-microbial, and anti-cancer, have been reported, the anti-adipogenic activity of cortex ulmi pumilae remains unclarified. In the present study, we investigated the effect of cortex ulmi pumilae extract on adipocyte differentiation in 3T3-L1 preadipocytes. Treatment with cortex ulmi pumilae extract significantly reduced the formation of lipid droplets and triglyceride content in a dose-dependent manner; this is associated with an inhibition of the adipogenic transcription factors, CCAAT/enhancer binding protein ${\alpha}$ ($C/EBP{\alpha}$), $C/EBP{\beta}$, and peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$). In addition, cortex ulmi pumilae extract treatment during the early stage of adipogenesis showed more efficient anti-adipogenic activity than treatment during other stages of adipogenesis. Cortex ulmi pumilae extract also inhibited cell proliferation and induced G1 arrest of 3T3-L1 cells in the early stage of adipogenesis. This was associated with upregulated expression of Cdk inhibitor p21 and downregulated expression of cyclin E and phospho-Rb, indicating that cortex ulmi pumilae extract blocks mitotic clonal expansion by cell cycle regulation. Taken together, these results suggest that cortex ulmi pumilae extract possesses anti-adipogenic activity through the inhibition of adipocyte differentiation by blocking mitotic clonal expansion.

• Korean Journal of Poultry Science
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• v.33 no.2
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• pp.97-103
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• 2006

Telomeres are essential for chromosome stability and are related with cell senescence, apoptosis and cancer. Even though telomere length and telomerase activity have been studied extensively, very little is known to analyze the telomere dynamics in chicken cells. This study was carried out to analyze the telomere distribution and telomerase activity of Korean Native Chicken cells along with aging. The cells were collected from brain, heart, liver, kidney and germinal tissues during physiological stages. Telomere distribution was analyzed by Quantitative-Fluorescence in situ Hybridization (Q-FISH) techniques using the chicken telomeric DNA probe. Telomerase activity was performed by Telomeric Repeat Amplification Protocol (TRAP) assay. In results, the telomeres of chicken were found at the ends of all chromosomes with the interstitial telomeres on chromosomes 1, 2 and 3. The amount of telomeres on chicken cells was decreased along with aging in most tissues. Furthermore, the telomere quantity was significantly different among tissues. The relative amount of telomeres in proliferous cells such as testis cells had much more than those of liver, brain, heart, blood and kidney cells. The telomerase activity was down-regulated in cells of brain, heart and liver tissues. Whereas gonadal cells showed a constitutive activity of telomerase during all stage of life. In conclusions, the telomere quantity and telomerase activity in chicken are closely relate to cell proliferation and tissue specificity during developmental stages and aging. There is also closely correlated between the amounts of telomeric DNA and telomerase activity in chicken tissues.

• Radiation Oncology Journal
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• v.15 no.3
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• pp.197-206
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• 1997

Purpose : Phospholipase D (PLD) catalyzes the hydrolysis of phosphatidylcholine to phosphatidic acid (PA) and choline. Recently, PLD has been drawing much attentions and considered to be associated with cancer Process since it is involved in cellular signal transduction. In this experiment, oleate-PLD activities were measured in various tissues of the living rats after whole body irradiation. Materials and Methods : The reaction mixture for the PLD assay contained $0.1\;\muCi\;1,2-di[1-^{14}C]palmitoyl$ phosphatidylcholine 0.5mM phosphatidylcholine, 5mM sodium oleate, $0.2\%$ taurodeoxycholate, 50mM HEPES buffer(pH 6.5), 10mM $CaCl_2$, and 25mM KF. phosphatidic acid, the reaction product, was separated by TLC and its radioactivity was measured with a scintillation counter. The whole body irradiation was given to the female Wistar rats via Cobalt 60 Teletherapy with field size of 10cmx loom and an exposure of 2.7Gy per minute to the total doses of 10Gy and 25Gy. Results : Among the tissues examined, PLD activity in lung was the highest one and was followed by kidney, skeletal muscle, brain, spleen, bone marrow, thymus, and liver. Upon irradiation, alteration of PLD activity was observed in thymus, spleen, lung, and bone marrow. Especially PLD activities of the spleen and thymus revealed the highest sensitivity toward $\gamma-rar$ with more than two times amplification in their activities In contrast, the PLD activity of bone marrow appears to be reduced to nearly $30\%$. Irradiation effect was hardly detected in liver which showed the lowest PLD activity. Conclusion : The PLD activities affected most sensitively by the whole-body irradiation seem to be associated with organs involved in immunity and hematopoiesis. This observation s1ron91y indicates that the PLD is closely related to the physiological function of these organs, Furthermore, radiation stress could offer an important means to explore the phenomena covering from cell Proliferation to cell death on these organs.

• Journal of Oral Medicine and Pain
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• v.36 no.1
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• pp.11-20
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• 2011

Valproic acid (VPA) is a well-known anticonvulsive agent and has been used in the treatment of epilepsy for almost 30 years. VPA emerged in 1997 as an antineoplastic agent. And it is known that antitmor activity of VPA is associated with its targeted at histone deacetylases. 17AAG, Inhibition of HSP90 leads to the proteasome degradation of the HSP90 client proteins, such as Akt, Raf/Ras, Erk, VEGF, cyclin D and p53, and causes potent antitumor activity. It is reported that 17AAG-induced HSP90 inhibition results in prevention of cell proliferation and induction of apoptosis in several types of cancer. This study was undertaken to investigate the synergistic apoptotic effect of co-treatment with the histone deacetylases inhibitor, VPA and the HSP90 inhibitor, 17AAG on human osteosarcoma (HOS) cells. Cell viability was evaluated by trypan-blue exclusion. Induction and augmentation of apoptosis were confirmed by Hoechst staining, flow cytometry (DNA hypoploidy and MMP change), Westen blot analysis and immunofluorescent staining. In this study, HOS cells co-treated with VPA and 17AAG showed several lines of apoptotic manifestation such as nuclear condensations, the reduction of MMP, the decrease of DNA content, the release of cytochrome c into cytosol, the translocation of AIF onto nuclei, and activation of caspase-3, caspase-7 and PARP whereas each single treated HOS cells did not. Although the single treatment of 1 mM VPA or 0.5 ${\mu}M$ 17AAG for 48 h did not induce apoptosis, the co-treatment with them induced prominently apoptosis. Therefore our data in this study provide the possibility that combination therapy with VPA and 17AAG could be considered as a novel therapeutic strategy for human osteosarcoma.

• Journal of Life Science
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• v.23 no.4
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• pp.501-509
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• 2013

Formaldehyde (FA) is widely used in industries, and it is an indoor and outdoor pollutant. Exposure to FA may cause inflammation and respiratory oxidative stress. Studies have demonstrated that FA can cause cancer in animal models. During the regeneration process of injured starfish (Asterina pectinifera), several changes have been observed in the expression of cytokines. In particular, higher TGF-${\beta}1$ expression has been detected in arm cut starfish extract after eight days. The current study was designed to elucidate the in-vitro and the in-vivo pharmacological effects of starfish extract on FA exposure. We investigated the protective effects of intact starfish extract and arm cut starfish extract on an IMR-90 cell line and on mouse lung injury in response to FA exposure. In the presence of FA, inhalation of the arm cut starfish extract was associated with more promising cell proliferation, TNF-${\alpha}$, NF-${\kappa}B$ decrement, and $I{\kappa}-B{\alpha}$ increment. In the experimental group, the pulmonary structure of the arm cut starfish extract-treated group in the presence of FA exposure was similar to the control group, whereas the FA exposure group showed damage to the pulmonary structure. Moreover, the arm cut starfish extracts was more effective than the intact starfish extracts in terms of the expression of TNF-${\alpha}$, NF-${\kappa}B$, $I{\kappa}-B{\alpha}$, and surfactant protein A. The results obtained in this study demonstrate that arm cut starfish extracts are more effective in protecting pulmonary structure and function against FA exposure than intact starfish extracts.

• Journal of Life Science
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• v.30 no.11
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• pp.931-938
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• 2020

Translationally controlled tumor protein (TCTP) is one of the most abundant proteins in various eukaryotic organisms. TCTPs play important roles in cell physiological processes in cancer, cell proliferation, gene regulation, and heat shock response. TCTP is also considered an important factor in the resistance to oxidative stress induced by dithiothreitol or hydrogen peroxide (H₂O₂). Arctic calanoid copepods have a variety of antioxidant defense systems to regulate the levels of potentially harmful reactive oxygen species generated by ultraviolet radiation in the Arctic marine ecosystem. However, information on the antioxidant activity of TCTP in the Arctic Calanus glacialis is still scarce. To understand the putative antioxidant function of the Arctic copepod C. glacialis TCTP (Cg-TCTP), its gene was cloned and sequenced. The Cg-TCTP comprised 522 bp and encoded a 174-amino acid putative protein with a calculated molecular weight of ~23 kDa. The recombinant Cg-TCTP (Cg-r TCTP) gene was overexpressed in Escherichia coli (BL21), and Cg-rTCTP-transformed cells were grown in the presence or absence of H₂O₂. Cg-rTCTP-transformed E. coli showed increased tolerance to high H₂O₂ concentrations. Therefore, TCTP may be an important antioxidant protein related to tolerance of the Arctic copepod C. glacialis to oxidative stress in the harsh environment of the Arctic Ocean.

• Journal of the Korean Society of Food Science and Nutrition
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• v.38 no.11
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• pp.1535-1542
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• 2009

To find the new use of Korean ginseng and mushroom, crude polysaccharides were prepared from submerged cultures of Hericium erinaceum in the medium supplemented with Korean ginseng extracts. When we fractionated crude polysaccharides (HE-GE-CP-1, 3, and 5) from hot-water extracts of submerged cultures of H. erinaceum with ginseng extracts (1%, 3%, and 5% addition of total medium), the yields of HE-GE-CP-1, 3, and 5 were identified at 5.7, 5.1, and 4.8%, respectively. Among crude polysaccharide fractions, HE-GE-CP-5 was significantly higher (1.89-fold of the saline control) than those of HE-GE-CP-1 (1.64-fold) or HE-GE-CP-3 (1.76-fold) on mitogenic activity of splenocytes. HE-GE-CP-5 also had the more potent bone marrow cell proliferation (1.83-fold) rather than HE-CP or HE-GE-CP-1 or HE-GE-CP-3 (1.59- or 1.44- or 1.69-fold, respectively), and anti-metastatic activity as anti-cancer effect showed the highest prophylactic value (72.4% inhibition of tumor control) in 5% supplementation of ginseng extract. However, the lysosomal phosphatase of macrophage was significantly stimulated after HE-GE-CP-3 treatment (2.03-fold). In addition, the immunostimulating and anti-metastatic crude polysaccharide, HE-GE-CP-5, contained mainly neutral sugars (63.2%) with considerable amounts of uronic acid (19.3%) and a small amount of proteins (8.8%). HE-GE-CP-5 can stimulate immune system to inhibit tumor metastasis, and its anti-tumor metastasis may be associated with macrophages, splenocytes and Peyer's patch cells activation.

• Journal of Life Science
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• v.29 no.4
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• pp.410-420
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• 2019

Citrus unshiu peel extracts possess a variety of beneficial effects, and studies on their anticancer activity have been reported. However, the exact mechanisms underlying this activity remain unclear. In the current study, the apoptotic effect of ethanol extract of C. unshiu peel (EECU) on human breast adenocarcinoma MDA-MB-231 cells and related mechanisms were investigated. The results showed that the survival rate of MDA-MB-231 cells treated with EECU was significantly inhibited in a concentration-dependent manner, which was associated with the induction of apoptosis. EECU-induced apoptosis was associated with the activation of caspase-8 and caspase-9, which initiate extrinsic and intrinsic apoptosis pathways, respectively, and caspase-3, a representative effect caspase. EECU suppressed the expression of the inhibitor of apoptosis family of proteins, leading to an increased Bax/Bcl-2 ratio and proteolytic degradation of poly (ADP-ribose) polymerase. EECU also enhanced the loss of the mitochondrial membrane potential and cytochrome c release from the mitochondria to the cytosol, along with truncation of Bid. In addition, EECU activated AMP-activated protein kinase (AMPK), and compound C, an AMPK inhibitor, significantly weakened EECU-induced apoptosis and cell viability reduction. Furthermore, EECU promoted the generation of reactive oxygen species (ROS), which acted as upstream signals for AMPK activation as pretreatment of cells, with the antioxidant N-acetyl cysteine reversing both EECU-induced AMPK activation and apoptosis. Collectively, these findings suggest that EECU inhibits MDA-MB-231 adenocarcinoma cell proliferation by activating intrinsic and extrinsic apoptotic pathways, which was mediated through ROS/AMPK-dependent pathways.