• Tuberculosis and Respiratory Diseases
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• v.56 no.6
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• pp.638-645
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• 2004

Background : Uteroglobin is a protein produced by the normal bronchial epithelium and its expression level is lower in non-small cell lung cancer tissues and cell lines. It mainly functions as an anti-inflammatory, and when it is overexpressed in cancer cells, the neoplastic phenotype is antagonized. cPLA2 and COX-2, which are also associated with inflammation, were reported to be related to cancer. The relationship between cPLA2, COX-2 and uteroglobin is unclear. The relationship between uteroglobin and ERK, which is related to cell growth, is also not unclear. This study investigated the changes in the cPLA2 and COX-2 expression levels and the ERK activities after the overexpression of uteroglobin in non-small cell lung cancer cell lines. Methods : The A549 and NCI-H460 cell lines were infected by adenovirus-null and adenovirusuteroglobin. The cChange in the cPLA2, COX-2 expression level and ERK activity after uteroglobin overexpression was measured by Western blot. The change in MMP activity was measured by zymography. Results : Western blot revealed decreased expression levels of cPLA2, and COX-2, and increased pERK levels in nonsmall cell lung cancer cells after uteroglobin overexpression. Zymography revealed no changes in the MMP-2 activity and lower MMP-9 activity. U0126, which is a specific inhibitor of ERK-activating kinase MEK-1/-2, prevented the decrease in the MMP-9 activity Conclusions : A decrease in cPLA2 expression, COX-2 expression, MMP-9 activity and a increase in ERK activity may be related to the anticancer effects of uteroglobin in nonsmall cell lung cancer cells.

• Journal of Life Science
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• v.28 no.8
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• pp.945-954
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• 2018

Omega-3 polyunsaturated fatty acids (${\omega}3$-fatty acid) have been found to possess anticancer properties in a variety of cancer cell lines and animal models, but their effects in human tongue squamous cell carcinomas (SCCs) remain unclear. This study was designed to examine the effect of ${\omega}3$-fatty acid desaturase (fat-1) gene expression on invasion and tumorigenicity in human tongue SCC cells and the molecular mechanism of its action. Docosahexaenoic acid (DHA) treatment inhibited in vitro invasion in a dose-dependent manner. In zymography, matrix metalloproteinase-9 (MMP-9) and Matrix metallopeptidase-2 (MMP-2) activities were reduced, and MMP-9 and MMP-2 promoter activities were inhibited by the DHA treatment. In addition, cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) promoter reporter activities were inhibited in SCC-4 and SCC-9 cells after the DHA treatment. To investigate the effect of a high level of endogenous ${\omega}3$ fatty acids, a stable SCC-9 cell line expressing the ${\omega}3$-desaturase gene (fSCC-9sc) was generated. The growth rate and colony-forming capacity of fSCC-9sc were remarkably decreased as compared with those of fSCC-9cc. Likewise, the tumor size and volume of fSCC-9sc implanted into nude mice were significantly inhibited, with increases in the cell death index. Furthermore, a transwell chamber invasion assay showed a reduction in cell invasion of the fSCC-9sc lines when compared with that of the fSCC-9cc line. These findings suggested that fat-1 gene expression inhibited tumorigenicity, as well as invasion in human tongue SCC cells. Thus, utilization of ${\omega}3$ fatty acids may represent a promising therapeutic approach for chemoprevention and the treatment of human tongue SCCs.

• Applied Microscopy
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• v.32 no.4
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• pp.385-398
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• 2002

The purpose of the present study is to investigate whether stromal cells supporting specific microenvironment for hematopoiesis of bone marrow are affected by toxicants and therapeutic drugs such as antibiotics and anticancer drugs and whether laminin-1 is associated with such effects. SD rats were intraperitoneally injected with 75 mg/kg of cyclophosphamide which is widely used to treat infant's solid tumor, leukemia and myeloma and sacrificed after 3 days, 1 week, 3 weeks or 5 weeks of injection. The bone marrow extracted and paraffin-sectioned was analyzed using immunohistochemical staining. A part of tissues was subjected to electron microscopy following reaction with rabbit anti-laminin antibody, biotinylated goat anti-rabbit IgG conjugated with 12 nm gold particles, and staining with uranyl acetate. 1. The bone marrow tissue at day 3 post injection with cyclophosphamide displayed dilated venous sinus, partial necrotic death, and decreased number of hematopoietic cells. Laminin-1 was intensively stained in the reticular and adipose tissues. 2. Up to 5 weeks post injection, laminin-1 was stained at a low level in the stromal tissue of bone marrow and the number of hematopoietic cell was increased. 3. Deposition of the gold particle which represents laminin-1 expression was observed at the highest level in the stromal cells of bone marrow obtained 3 days after injection, and decreased after 1 to 5 weeks. These results suggest that stromal cells which play a role in supporting microenvironment for bone marrow hematopoiesis augment induction of laminin-1 expression and activation upon administration of cyclophosphamide.

• Journal of Life Science
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• v.22 no.6
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• pp.760-771
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• 2012

Marine triterpene glycosides are physiologically active natural compounds isolated from sea cucumbers(holothurians). It was demonstrated that they have a wide range of biological activities, including antifungal, cytotoxic, and antitumor effects. A previous study showed that stichoposide C (STC) isolated from Thelenota anax induces apoptosis through generation of ceramide by activation of acid sphingomyelinase (SMase) and neutral SMase in human leukemia cells. In this study, we investigated whether STD, a structural analog of STC, can induce apoptosis and examined the molecular mechanisms for its activity. It was found that STC and STD induce apoptosis in a dose- and time-dependent manner and lead to the activation of caspase-8, mitochondrial damage, activation of caspase-9, and activation of caspase-3 in K562 and HL-60 cells. STC activates acid SMase and neutral SMase, which results in the generation of ceramide. Specific inhibition of acid SMase or neutral SMase partially blocked STC-induced apoptosis, but not STD-induced apoptosis. In contrast, STD generates ceramide through the activation of ceramide synthase. Specific inhibition of ceramide synthase partially blocked STD-induced apoptosis, but not STC-induced apoptosis. Moreover, STC and STD markedly reduced tumor growth of HL-60 xenograft tumors and increased ceramide generation in vivo. These results indicate that STC and STD can induce apoptosis and have antitumor activity through the different molecular mechanisms, because they have a different sugar residue attached to aglycones. Thus, these results suggest that their actions are affected by a sugar residue attached to aglycones and they can be used as anticancer agents in the treatment of leukemia.

• The Journal of the Korean bone and joint tumor society
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• v.15 no.2
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• pp.111-121
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• 2009

Background: Osteosarcoma is one of the most common primary malignant tumors of bone occurring mainly in children and adolescents. Although surgery combined with chemotherapy has markedly improved patient survival during the last years, the use of anticancer drugs is still associated with serious problem, such as the frequent acquisition of drug-resistant phenotypes and occurrence of "secondary malignancies". Several solid tumors display enhanced expression of matrix metalloproteinases (MMPs), and recently clinical trials have been initiated on MMP-inhibitors. On the other hand, bisphosphonates (BPs) are inhibitors of bone resorption, and widely used to treat osteoclast-mediated bone diseases. Also they appear to possess direct antitumor activity. Methods: One osteosarcoma cell line (U2OS) was treated with ibandronate (0, 0.1, 1, $10{\mu}M$) for 48 hours. Cell viabilities were determined using MTT assay, the mRNA levels of MMP-2 and MT1-MMP were detected by reverse-transcription polymerase chain reaction, the amount of MMP-2 and MT1-MMP protein were measured by Westernblot, the activities of MMP-2 were observed by Gelatin zymography, and Matrigel invasion assays were used to investigate the invasive potential of osteosarcoma cell lines before and after ibandronate treatment. Results: The invasiveness of U2OS cell line was reduced dose-dependently following 48 hour treatment of up to $10{\mu}M$ of the ibandronate at which concentration no cytotoxicity occurred. Furthermore, the gelatinolytic activities and protein and mRNA levels of MMP-2 and MT1-MMP were also suppressed by increasing ibandronate concentrations. Conclusion: Given that MMP-2 is instrumental in tumor cell invasion, it is very likely that the reduction in osteosarcoma cell invasion by ibandronate is a consequence, at least in part, of suppressed expression of both MMP-2 and MT1-MMP. Isolation of a molecule (s) responsible for the bisphosphonate inhibition of tumor cell invasion would pave the way for the development of a new generation of metastasis inhibitors.

• Journal of Food Hygiene and Safety
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• v.23 no.3
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• pp.264-270
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• 2008

Phytic acid(PA) (Inositol hexaphosphate, $IP_6$) is a naturally occurring polyphosphorylated carbohydrate that is present in substantial amounts in almost all plants and mammalian cells. Recently PA has received much attention for its role in anticancer activity. In the present study, the preventive effects of PA on colon carcinogenesis were investigated. Six-week old Fisher 344 male rats were fed a AIN-93G purified diet and PA(0.5% or 2% PA in water) for 8 weeks. The animals received two ($1^{st}\;and\;2^{nd}$ week) injections of azoxymethane(AOM, 15 mg/kg b.w.) to induce colonic aberrant crypt foci(ACF). After sacrifice, the total numbers of aberrant crypts(AC) and ACF in colonic mucosa were examined after staining with methylene blue. Blood and serum were analyzed with a blood cell differential counter and an automatic serum analyzer. AOM induced the total numbers of $142.3{\pm}22.3$ ACF/colon and $336.6{\pm}55.1$ AC/colon. PA at the doses of 0.5 and 2% decreased the numbers of ACF and AC/colon in a dose-dependent manner. The numbers of ACF/colon and AC/colon by PA at the dose of 0.5% were $124.4{\pm}28.5\;and\;302.7{\pm}67.3$, respectively. PA at the dose of 2% significantly decreased the ACF and AC numbers to $109{\pm}18.1\;and\;254.8{\pm}50.6$, respectively(p<0.01). Especially, 2% PA significantly reduced the number of large ACF(${\geq}4$ AC/ACF) from $26.8{\pm}6.2$ ACF/colon to $15{\pm}6.7$ ACF/colon(p<0.01). Although some parameters in blood counts and serum chemistry were changed compared with the control, no specific toxicity was found. These findings suggest that phytic acid can be a chemopreventive agent for colon carcinogenesis resulting from inhibition of the development of ACF in the F344 rat.

• 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 the Korean Society of Food Science and Nutrition
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• v.41 no.5
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• pp.584-590
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• 2012

Dried $Compositae$ flowers have traditionally been used for the treatment of anti-inflammatory and anti-oxidative stress in Korea. This paper investigates the effects of $Compositae$ extracts on the inhibition of proliferation and apoptosis of human gastric cancer AGS cells, human breast cancer MDA-MB-231 cells, and SK-BR-3 cells. The proliferation of AGS cells, MDA-MB-231 cells, and SK-BR-3 cells were determined by MTT assay. Several $Compositae$ extracts inhibited proliferation of AGS cells, MDA-MB-231 cells, and SK-BR-3 cells in a dose-dependent manner. To assess the apoptosis of $Compositae$ extracts, the nuclei of MDA-MB-231 cells were stained with DAPI. The presence of chromatin condensation in the $Compositae$ extract-treated cells was detected on a fluorescent microscope (${\times}200$). We conducted Western blot analysis of changes in Bcl-2, Bax, and p53 protein expression levels. Apoptosis by $Chrysanthemum$ $zawadskii$ subsp. coreanum, $Chrysanthemum$ $zawadskii$ var. $tenuisectum$ and $Rudbeckia$ $laciniata$ var. $hortensis$ treatment created a decrease in Bcl-2 expression, whereas the expression of Bax and p53 were increased. These results indicate that $Chrysanthemum$ $zawadskii$ $subsp.$ $coreanum$, $Chrysanthemum$ $zawadskii$ var. $tenuisectum$ and $Rudbeckia$ $laciniata$ var. $hortensis$ inhibit breast cancer cell growth through the induction of apoptosis.

• Tuberculosis and Respiratory Diseases
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• v.66 no.2
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• pp.93-97
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• 2009

Background: Belotecan (Camtobell, CKD-602, Chongkundang Pharm., Korea), a camptothecin derivative, has anticancer effects by inhibiting topoisomerase I such as topotecan. This study observed the response, survival and toxicity of belotecan monotherapy after the failure of etoposide and platinum (EP). Methods: Forty nine small cell lung cancer (SCLC) patients (M/F=41/8; age, 64.5${\pm}$7.6 (mean${\pm}$SD) years), who failed in their first line chemotherapy were enrolled in this study. Twenty one SCLC patients showed relapsed lung cancer more than 90 days after their priorEP chemotherapy (sensitive relapse group, SR) and 28 patients relapsed within 90 days (refractory relapse group, RR). Results: The response rate was 25%. Eleven patients showed partial responses and 5 patients could not be checked. The response rate of the SR and RR patients was similar. The relative dose intensity was lower in the responders (78${\pm}$15%) than non-responders (83${\pm}$13%, p=0.03). The median survival time (MST) was 10.3 months (290 days). The MST of the non-responders and responders was 186 days (95% CI; 67-305) and 401 days (95% CI; 234-568, p=0.07), respectively. The median progression free survival (MPFS) was similar in the SR (79 days) and RR (67 days) patients. Grade 3-4 neutropenia, anemia, and thrombocytopenia were observed in 59.6%, 12.8% and 23.4% of patients, respectively. Conclusion: The efficacy and survival were demonstrated in the second-line setting. However, a randomized comparative trial with topotecan will be needed.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.4
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• pp.520-526
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• 2013

To determine the kimchi with the best quality and functional characteristics, we manufactured and compared recipes for Korean and Japanese kimchi made either Korean or Japanese baechu cabbages. All batches were fermented for 4 weeks at $5^{\circ}C$, and tested for pH, texture, microbial count, sensory evaluation, DPPH radical-scavenging activity, and cell proliferation (using the MTT assay on AGS human gastric cancer cells). By the third week of fermentation, Korean kimchi made with Korean baechu (KK) and Japanese kimchi made with Korean baechu (KJ) showed a higher acidity than Korean or Japanese kimchi made with Japanese baechu (JK and JJ, respectively). KK ranked highest in springiness, followed by KJ, JK, and JJ. Therefore, the texture of kimchi produced with Korean baechu was appears better than kimchi produced with Japanese baechu. This was confirmed in masticatory tests. Kimchi produced with Korean baechu (KK and KJ) showed lower total aerobic bacterial counts, while the total lactic acid bacterial counts were higher (p<0.05). In sensory evaluation test, KK received the highest overall acceptability score, while JJ earned the lowest score. In the DPPH assay for anti-oxidative activity, KK showed a 94% anti-oxidative effect, followed by KJ (92%), JK (91%), and JJ (88%) (p<0.05). In the MTT assay for analyzing the cell proliferation of AGS human gastric cancer cells, KK showed a 64% anticancer effect in vitro, followed by KJ (57%), JK (38%), and JJ (26%). Therefore, the anti-oxidative and anti-cancer functionalities of kimchi made with Korean baechu were higher than those made with Japanese baechu, regardless of the kimchi recipe applied. Overall, Korean baechu had important and superior effects on the quality and functionality of kimchi.