• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.4
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• pp.516-523
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• 2015

This study investigated the antimutagenic and anticancer effects of Platycodon grandiflorum extract (PGE) and its fractions against carcinogenic N-nitrosodimethylamine (NDMA) and genotoxicity. The Ames Salmonella mutagenicity test employing histidine mutants of Salmonella Typhimurium TA98 and TA100 was used to examine the mutagenicity of PGE and its fractions. Bacterial reversion assay with S. Typhimurium TA98 and TA100 did not show a significantly increased number of revertant colonies. The same test was used to examine the ability of PGE and its fractions to prevent acquisition of N-methyl-N'-nitro-N-nitrosoguanidine- and 4-introquino-line-1-oxide-induced mutations. PGE and its fractions inhibited mutagenesis in a dose-dependent manner. Among the fractions, ethyl acetate fraction from PGE (PGEA) exhibited a higher antimutagenic effect than other fractions. PGE and its fractions suppressed the growth of cancer cell lines, including human cervical adenocarcinoma, human hepatocellular carcinoma, human breast adenocarcinoma, human lung carcinoma, and transformed primary human embryonic kidney cells. In addition, we evaluated the antitumor activity of PGEA and its fractions in sacorma-180 solid tumor-bearing mice. In vivo anticancer activity results showed that PGE and its fractions could more effectively suppress tumor growth than the control. PGEA showed higher in vitro and in vivo anticancer effects than PGE and other fractions, and PGEA inhibited NDMA formation. Thus, we showed that PGEA has antimutagenic and anticancer activities, making it a candidate anticancer material under these experimental conditions.

• Journal of Life Science
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• v.18 no.10
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• pp.1395-1399
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• 2008

We have recently reported the PRC1 promoter as a promoter candidate to control expression of transcriptionally targeted genes for breast cancer gene therapy. We tested whether the PRC1 promoter could be also applied for the lung cancer gene therapy. In the transient transfection assay with naked plasmids containing the luciferase fused to the PRC1 promoter, the promoter showed little activity in the normal lung cell line, MRC5. However, in the lung cancer A549 cells, PRC1 showed approximately 30-fold activation which was similar to the survivin promoter, the gene whose promoter has been already reportedas a candidate for the gene therapy of lung cancer. In viral systems, the PRC1 promoter showed approximately 75% and 66% of transcriptional activity compared to the CMV promoter in the adeno-associated virus (AAV) and the adenovirus (AV) systems, respectively. However, the PRC1 promoter in either AAV or AV showed approximately 20% activity compared to the CMV promoter in the normal lung cells. In addition, human lung tumor xenograft mice showed that the PRC1 promoter activity was as strong as the CMV activity in vivo. Taken together, these results suggested that PRC1 might be a potential promoter candidate for transcriptionally targeted lung cancer gene therapy.

• Tuberculosis and Respiratory Diseases
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• v.79 no.3
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• pp.143-152
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• 2016

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterized by the accumulation of excessive fibroblasts and myofibroblasts in the extracellular matrix. The transforming growth factor ${\beta}1$ (TGF-${\beta}1$)-induced epithelial-to-mesenchymal transition (EMT) is thought to be a possible source of fibroblasts/myofibroblasts in IPF lungs. We have previously reported that apolipoprotein A1 (ApoA1) has anti-fibrotic activity in experimental lung fibrosis. In this study, we determine whether ApoA1 modulates TGF-${\beta}1$-induced EMT in experimental lung fibrosis and clarify its mechanism of action. Methods: The A549 alveolar epithelial cell line was treated with TGF-${\beta}1$ with or without ApoA1. Morphological changes and expression of EMT-related markers, including E-cadherin, N-cadherin, and ${\alpha}$-smooth muscle actin were evaluated. Expressions of Smad and non-Smad mediators and TGF-${\beta}1$ receptor type 1 ($T{\beta}RI$) and type 2 ($T{\beta}RII$) were measured. The silica-induced lung fibrosis model was established using ApoA1 overexpressing transgenic mice. Results: TGF-${\beta}1$-treated A549 cells were changed to the mesenchymal morphology with less E-cadherin and more N-cadherin expression. The addition of ApoA1 inhibited the TGF-${\beta}1$-induced change of the EMT phenotype. ApoA1 inhibited the TGF-${\beta}1$-induced increase in the phosphorylation of Smad2 and 3 as well as that of ERK and p38 mitogen-activated protein kinase mediators. In addition, ApoA1 reduced the TGF-${\beta}1$-induced increase in $T{\beta}RI$ and $T{\beta}RII$ expression. In a mouse model of silica-induced lung fibrosis, ApoA1 overexpression reduced the silica-mediated effects, which were increased N-cadherin and decreased E-cadherin expression in the alveolar epithelium. Conclusion: Our data demonstrate that ApoA1 inhibits TGF-${\beta}1$-induced EMT in experimental lung fibrosis.