• Tuberculosis and Respiratory Diseases
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• v.72 no.4
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• pp.343-351
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• 2012

Background: The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling axis has emerged as a novel target for cancer therapy. Agents that inhibit this pathway are currently under development for lung cancer treatment. In the present study, we have tested whether dual inhibition of PI3K/Akt/mTOR signaling can lead to enahnced antitumor effects. We have also examined the role of autophagy during this process. Methods: We analyzed the combination effect of the mTOR inhibitor, temsirolimus, and the Akt inhibitor, GSK690693, on the survival of NCI-H460 and A549 non-small cell lung cancer cells. Cell proliferation was determined by MTT assay and apoptosis induction was evaluated by flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Autophagy induction was also evaluated by acridine orange staining. Changes of apoptosis or autophagy-related proteins were evaluated by western blot analysis. Results: Combination treatment with temsirolimus and GSK690693 caused synergistically increased cell death in NCI-H460 and A549 cells. This was attributable to increased induction of apoptosis. Caspase 3 activation and poly(ADP-ribose) polymerase cleavage accompanied these findings. Autophagy also increased and inhibition of autophagy resulted in increased cell death, suggesting its cytoprotective role during this process. Conclusion: Taken together, our results suggest that the combination of temsirolimus and GSK690693 could be a novel strategy for lung cancer therapy. Inhibition of autophagy could also be a promising method of enhancing the combination effect of these drugs.

• Journal of Applied Biological Chemistry
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• v.57 no.2
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• pp.113-122
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• 2014

A5E is complex of several medicinal herb ethanol extracts. The aim of this study is investigating the anticancer effect for non-small cell lung cancer. The antitumor effects of A5E on NCI-H460 were examined by regulation of cell proliferation, apoptosis, cell cycle arrest, mitochondrial membrane potential (${\Delta}{\Psi}_m$), and apoptosis-related protein. Cell proliferation was measured by MTS assay. Apoptosis induced by A5E was confirmed by Annexin V-fluorescein isothiocyanate (FITC)/Propidium Iodide (PI) staining, and cell cycle arrest was measured by PI staining. NF-${\kappa}B$ translocation was detected by immunofluorescence and MMP (${\Delta}{\Psi}_m$) was measured by JC-1 staining. The expression of extrinsic pathway molecules such as FasL and FADD were elevated, and procaspase-8 was processed by A5E. In addition, intrinsic pathway related molecules were altered. The Bcl-2 and Bcl-xl levels decreased, Bax increased, and cytochrome C was released. In addition, the mitochondrial membrane potential collapsed, and caspase-3 and poly-(ADP-ribose) polymerase were processed by A5E. Moreover, A5E affected the cellular survival pathway involving phosphatidylinositol 3-kinase (PI3K)/Akt and NF-${\kappa}B$. PI3K and Akt were downregulated, also NF-${\kappa}B$ expression was decreased, and nuclear translocalization was inhibited by A5E. These results suggested that A5E delays proliferation, inhibit cell cycle progression and induce apoptosis in human lung cancer cell. We conclude that A5E is a potential anticancer agent for human lung carcinoma.

• Tuberculosis and Respiratory Diseases
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• v.60 no.3
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• pp.304-313
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• 2006

Background : Heme oxygenase-1 (HO-1) is an inducible enzyme that catalyzes the oxidative degradation of heme to form biliverdin, carbon monoxide (CO), and free iron. The current evidence has indicated a critical role of HO-1 in cytoprotection and also in other, more diverse biological functions. It is known that the high expression of HO-1 occurs in various tumors, and that HO-1 has an important role in rapid tumor growth because of its antioxidative and antiapoptotic effects. Therefore, the role of HO-1 was analyzed in human lung cancer cell lines, and especially in the A549 cell line. Material and Methods : Human lung cancer cell lines, i.e., A549, NCI-H23, NCI-H157 and NCI-H460, were used for this study. The expression of HO-1 in the untreated state was defined by Western blotting. ZnPP, which is the specific HO inhibitor we used, and the viability of cells were tested for by conducting MTT assaysy. The HO enzymatic activity, as determined via the bilirubin level, was also indirectly measured. Moreover, the generation of intracellular hydrogen peroxide (H2O2) was monitored fluorimetrically with using a scopoletin-horse radish peroxidase (HRP) assay and 2',7'-dichlorofluorescein diacetate (DCFH-DA). We have also transfected small HO-1 interfering RNA (siRNA) into A549 cells, and the apoptotic effects were evaluated by flow cytometric analysis and Western blotting. Results : The A549 cells had a greater expression of HO-1 than the other cell lines, whereas ZnPP significantly decreased the viability of the A549 cells more than the viability of the other lung cancer cells in a dose-dependant fashion. Consistent with the viability, the HO enzymatic activity also was decreased. Moreover, intracellular H2O2 generation via ZnPP was induced in a dose-dependent manner. Apoptotic events were, then induced in the HO-1 siRNA transfected A549 cells. Conclusion : HO-1 provides new important insights into the possible molecular mechanism of the antitumor therapy in lung cancer.

• Proceedings of the Korean Society for Bioinformatics Conference
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• 2001.08a
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• pp.139-149
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• 2001

Since 1990, the National Cancer Institute(NCI) has screened more than 60.000 compounds against a panel of 60 human cancer cell lines. The 50-percent growth-inhibitory concentration (GI$_{50}$) values encode unexpectedly rich, detailed information on mechanisms of drug action and drug resistance. Each compound's pattern is like a fingerprint, essentially unique among the many billions of distinguishable possibilities. These activity patterns are being used in conjunction with molecular structural features of the tested agents to explore the NCI's database of more than 460, 000 compounds, and they are providing insight into potential target molecules and modulators of activity in the 60 cell lines. For example, the information is being used to search for candidate anticancer drugs that are not dependent on intact p53 suppressor gene function for their activity. It remains to be seen how effective this information-intensive strategy will be at generating new clinically active agents.s.

• Journal of Life Science
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• v.18 no.8
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• pp.1140-1146
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• 2008

In order to improve the functional properties of kochujang, garic porridge was added to traditional kochujang during manufacturing. Changes in physiochemical properties of kochujang by garic porridge addition were then investigated. No big differences in general chemical compositions was observed between three kinds of kochujangs tested in this study, general kochujang purchased from a market (GK), kochujang added with raw garlic (RGK) and kochujang added with garlic porridge (GPK). However, GPK showed higher level of antioxidant and anticancer activities than those of others. The methanolic extract of GPK showed 66.38% of DPPH radical scavenging activity, while the extracts of GK and RGK exhibited 38.44% and 50.97%, respectively. Also, the effects of three different extracts of kochujangs on cell proliferation of stomach cancer cell (MKN 45), colon cancer cell (HCT116), and lung cancer cell (NCI-H460) were investigated using MTT assay. All of three extracts exhibited the highest anti-proliferative activity against stomach cancer cell, even though the proliferation of colon cancer cell and lung cancer cell were also inhibited. Among them, the extract of GPK showed the highest anti-proliferative activity (62.35%) against stomach cancer cell. From the results obtained in the present study, we concluded that the antioxidant and anticancer activity of GPK mainly originated from garlic because GPK was consisted of 23% garlic (w/w) compared to 10% (w/w) of RGK.

• Food Science and Biotechnology
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• v.18 no.3
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• pp.818-821
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• 2009

Total phenol, total flavonoid, reducing powder, electron donating activity, ascorbic acid equivalent antioxidant capacity, antimicrobial and antiproliferative activities of olive leaf extracts were investigated. The contents of total phenol and flavonoid were 257.48 and 92.33 mg in 100 g of olive leaf extract, respectively. The reducing power of the olive leaf extract increased with concentration increasing. Electron donating activity was high in 100 ${\mu}g/mL$ treated olive leaf extract as 95.20%. The ascorbic acid equivalent antioxidant capacity of the olive leaf extract was 68.93 mg/g olive leaf extract. The olive leaf extracts showed relatively high antimicrobial activity against Escherichia coli, Salmonella typhimurium, Bacillus cereus, Staphylococcus aureus, Listeria monocytogenes, and Pseudomonas aeruginosa. All of the cancer cell lines including MKN45, HCT116, NCI-H460, and MCF7 have 70-81% as effective growth inhibition.

• Environmental Mutagens and Carcinogens
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• v.26 no.4
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• pp.113-115
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• 2006

Ecklonia cava is a brown alga(Laminariaceae) that is abundant in the subtidal regions of Jeju island in Korea. Phlorotannins were identified to be responsible for the biological activities in Ecklonia species. In the present study, triphlorethol-A, a phlorotannin, was isolated from Ecklonia cava and its anticancer properties were investigated. Triphlorethol-A was investigated whether it may show cytotoxicity effects against U937, HeLa, NCI-H460 and MCF-7 cancer cells by MTT test. As a result, triphlorethol-A did not show cytotoxic effects against tested four cell lines.

• Tuberculosis and Respiratory Diseases
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• v.51 no.2
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• pp.122-134
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• 2001

Background : Some chemotherapeutic drugs induce NF-${\kappa}B$ activation by degrading the $I{\kappa}B{\alpha}$ protein in cancer cells which contributes to anticancer drug resistance. We hypothesized that inhibiting $I{\kappa}B{\alpha}$ degradation would block NF-${\kappa}B$ activation and result in increased tumor cell mortality in response to chemotherapy. Methods : The "superrepressor" form of the NF-${\kappa}B$ inhibitor was transferred by an adenoviral vector (Ad-$I{\kappa}B{\alpha}$-SR) to the human lung cancer cell lines (NCI H157 and NCI H460). With a MIT assay, the level of sensitization to cisplatin and paclitaxel were measured. To confirm the mechanism, an EMSA and Annexin V assay were performed. Results : EMSA showed that $I{\kappa}B{\alpha}$-SR effectively blocked the NF-${\kappa}B$ activation induced by cisplatin. Transduction with Ad-$I{\kappa}B{\alpha}$-SR resulted in an increased sensitivity of the lung cancer cell lines to cisplatin and paclitaxel by a factor of 2~3 in terms of $IC_{50}$. Annexin-V analysis suggests that this increment in chemosensitivity to cisplatin probably occurs through the induction of apoptosis. Conclusion : The blockade of chemotherapeutics induced NF-${\kappa}B$ activation by inducing Ad-$I{\kappa}B{\alpha}$-SR, increased apoptosis and increasing the chemosensitivity of the lung cancer cell lines tested, subsequently. Gene transfer of $I{\kappa}B{\alpha}$-SR appears to be a new therapeutic strategy of chemosensitization in lung cancer.

• 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 the Korean Society of Food Science and Nutrition
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• v.45 no.6
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• pp.918-922
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• 2016

The objective of this study was to determine the antioxidant and anti-proliferative activities of methanol, ethanol, acetone, and ethyl acetate extracts from oats (Avena sativa L.). Total polyphenol contents of extracts were analyzed by Folin-Ciocalteu assay. The antioxidant activities of extracts were determined by 2,2-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities and reducing power. The anti-proliferative activities of colon (HCT116), lung (NCI-H460), and breast (MCF7) cancer cells were investigated. Among solvents, methanol extract showed the highest amount of total polyphenols, which was 8.2 mg gallic acid equivalents/g residue. High levels of ABTS radical [12.1 mg Trolox equivalent antioxidant capacity (TEAC)/g residue] and DPPH radical (4.4 mg TEAC/g residue) scavenging activity and reducing power ($A_{700}=0.39$) were found in methanol extracts. Moreover, methanol extracts indicated higher anti-proliferative activities against HCT116 (69.5%), NCI-H460 (75.2%), and MCF7 (84.8%) cells compared with other extracts. The results show that methanol was the best solvent for extraction of antioxidant and anti-proliferative compounds from oats. Moreover, notable antioxidant and anti-proliferative activities of oats could have significant health benefits.