• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.2
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• pp.451-456
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• 2003

We investigated the effects of Sabaek-san (SBS) water extract on the growth of human lung carcinoma A549 cells. Upon treatment with SBS extract, a concentration-dependent inhibition of cell viability was observed and cells developed many of the hallmark features of apoptosis. including condensation of chromatin. Flow cytometry analysis confirmed that SBS treatment increased populations of apoptotic-sub G1 phase. In addition. proteolytic cleavages of poly(ADP-ribose) polymerase and β-catenin protein were observed after treatment of SBS extract. These apoptotic effects of SBS in A549 cells were associated with marked inhibition of Bcl-2 and Bel-xL mRNA in a dose-dependent manner. however the levels of Bax expression were not affected, SBS treatment also induced a proteolytic activation of caspase-3. which is believed to play a central role In the apoptotic signaling pathway. The previous and present results indicated that SBS-induced inhibition of lung cancer cell proliferation is associated with the blockage of G1/S progression and the induction of apoptosis.

• Journal of Microbiology and Biotechnology
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• v.21 no.7
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• pp.766-775
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• 2011

We investigated the effect of high molecular weight polygamma- glutamic acid (hm ${\gamma}$-PGA) on adiposity and lipid metabolism of rats in the presence of an obesity-inducing diet. Thirty-two Sprague-Dawley rats were fed either a normal-fat (11.4% kcal fat, NFC) or high-fat (51% kcal fat, HFC) diet. After 5 weeks, half of each diet-fed group was treated with hm ${\gamma}$-PGA (NFP or HFP) for 4 weeks. The HFC group had significantly higher body weight, visceral fat mass, fasting serum levels of total cholesterol, LDL cholesterol, and leptin, and lower serum HDL cholesterol level compared with those of the NFC group (p < 0.05). Treatment with hm ${\gamma}$-PGA decreased body weight gain and perirenal fat mass (p<0.05), fasting serum total cholesterol, and mRNA expression of glucose-6- phosphate dehydrogenase (G6PD), regardless of dietary fat contents (p < 0.01). However, hm ${\gamma}$-PGA increased serum HDL cholesterol in the HFC group (p < 0.05). In vitro, 3-hydroxy-3-methylglutaryl coenzyme-A (HMGCoA) reductase activity was suppressed by the addition of hm ${\gamma}$-PGA. In agreement with observations in animal study, the supplementation of hm ${\gamma}$-PGA (150 mg/day) to 20 female subjects in an 8-week double-blind, placebocontrolled study resulted in a tendency to decrease total cholesterol and LDL cholesterol concentrations. We thus conclude that dietary supplementation of hm ${\gamma}$-PGA may act as a hypocholestrolemic agent, secondary to its inhibitor effect on HMG-CoA reductase, and decrease abdominal adiposity by decreasing hepatic lipogenesis. The present study is an important first step in establishing the effect of hm ${\gamma}$-PGA on cholesterol levels in rats and humans.

• Journal of Ginseng Research
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• v.38 no.1
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• pp.8-15
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• 2014

Helicobacter pylori-induced gastric inflammation includes induction of inflammatory mediators interleukin (IL)-8 and inducible nitric oxide synthase (iNOS), which are mediated by oxidant-sensitive transcription factor NF-${\kappa}B$. High levels of lipid peroxide (LPO) and increased activity of myeloperoxidase (MPO), a biomarker of neutrophil infiltration, are observed in H. pylori-infected gastric mucosa. Panax ginseng Meyer, a Korean herb medicine, is widely used in Asian countries for its biological activities including anti-inflammatory efficacy. The present study aims to investigate whether Korean Red Ginseng extract (RGE) inhibits H. pylori-induced gastric inflammation in Mongolian gerbils. One wk after intragastric inoculation with H. pylori, Mongolian gerbils were fed with either the control diet or the diet containing RGE (200 mg RGE/gerbil) for 6 wk. The following were determined in gastric mucosa: the number of viable H. pylori in stomach; MPO activity; LPO level; mRNA and protein levels of keratinocyte chemoattractant factor (KC, a rodent IL-8 homolog), IL-$1{\beta}$, and iNOS; protein level of phospho-$I{\kappa}B{\alpha}$(which reflects the activation of NF-${\kappa}B$); and histology. As a result, RGE suppressed H. pylori-induced mRNA and protein levels of KC, IL-$1{\beta}$, and iNOS in gastric mucosa. RGE also inhibited H. pylori-induced phosphorylation of $I{\kappa}B{\alpha}$ and increases in LPO level and MPO activity of gastric mucosa. RGE did not affect viable H. pylori colonization in the stomach, but improved the histological grade of infiltration of poly-morphonuclear neutrophils, intestinal metaplasia, and hyperplasia. In conclusion, RGE inhibits H. pyloriinduced gastric inflammation by suppressing induction of inflammatory mediators (KC, IL-$1{\beta}$, iNOS), MPO activity, and LPO level in H. pylori-infected gastric mucosa.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.2
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• pp.553-560
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• 2004

In the present study, we investigated the anti-proliferative effects of aqueous extract of Wikyung-tang(WKT) on the growth of human lung carcinoma cell line A549. WKT treatment declined the cell viability and proliferation of A549 cells in a concentration-dependent manner. The anti-proliferative effects by WKT treatment in A549 cells was associated with morphological changes such as membrane shrinking and cell rounding up. WKT treatment induced an inhibition and/or degradation of apoptotic target proteins such poly(ADP-ribose) polymerase (PARP) and phospholipase C-γ1 (PLC-γ1). WKT treatment did not affect the levels of other Bcl-2 family gene products, such as Bcl-2, Bax and Bad. Western blot analysis and RT-PCT data revealed that the levels of tumor suppressor p53 and cyclin-dependent kinase inhibitor p21 were induced by WKT treatment in A549 cells. Additionally, WKT treatment induced the down-regulation of telomerase reverse transcriptase mRNA (hTERT) expression of A549 cells, however, the levels of other telomere-regulatory gene products were not affected. Taken together, these findings suggest that WKT-induced inhibition of human lung cancer cell proliferation is associated with the induction of apoptotic cell death via regulation of several major growth regulatory gene products and WKT may have therapeutic potential in human lung cancer.

• Journal of Microbiology and Biotechnology
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• v.30 no.6
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• pp.885-892
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• 2020

Chemotherapy regimens for non-small cell lung cancer (NSCLC) have various adverse effects on the human body. For this reason, probiotics have received attention regarding their potential value as a safe and natural complementary strategy for cancer prevention. This study analyzed the anticancer effects of aqueous extracts of probiotic bacteria Bifidobacterium bifidum (BB), Bifidobacterium longum (BL), Bifidobacterium lactis (BLA), Bifidobacterium infantis 1 (BI1), and Bifidobacterium infantis 2 (BI2) on NSCLC cell lines. When the aqueous extracts of probiotic Bifidobacterium species were applied to the NSCLC cell lines A549, H1299, and HCC827, cell death increased considerably; in particular, the aqueous extracts from BB and BLA markedly reduced cell proliferation. p38 phosphorylation induced by BB aqueous extract increased the expression of cleaved caspase 3 and cleaved poly (ADP-ribose) polymerase (PARP), consequently inducing the apoptosis of A549 and H1299 cells. When the p38 inhibitor SB203580 was applied, phosphorylation of p38 decreased, and the expression of cleaved caspase 3 and cleaved PARP was also inhibited, resulting in a reduction of cell death. In addition, BB aqueous extracts reduced the secretion of MMP-9, leading to inhibition of cancer cell invasion. By contrast, after transfection of short hairpin RNA shMMP-9 (for a knockdown of MMP-9) into cancer cells, BB aqueous extracts treatment failed to suppress the cancer cell invasiveness. According to our results about their anticancer effects on NSCLC, probiotics consisting of Bifidobacterium species may be useful as adjunctive anticancer treatment in the future.

• Journal of Microbiology and Biotechnology
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• v.16 no.10
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• pp.1570-1576
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• 2006

An encephalomyocarditis virus (EMCV-CBNU) was isolated from an aborted swine fetus in October 2005. To investigate the genetic origin and virulence of the EMCV-CBNU strain, we determined the complete sequence of the virus and tested its virulence in mice. Genetic characterization revealed that the RNA genome was composed of 7,713 nucleotides with a single open reading frame (2,292 amino acids), coding 12 proteins. The EMCV-CBNU had the shortest poly(C) tract, consisting of 10 C's ($C_{10}$), compared with all the other EMCV strains reported in GenBank. Amino acid and phylogenetic analyses showed that EMCV-CBNU had the highest genetic identity with strain 2887A (99.7%), which was originally isolated from a fetus in a pig breeding farm that had a history of reproductive failure. Because rodents are the natural host of EMCV, we investigated the virulence of EMCV-CBNU in mice. Surprisingly, all mice inoculated with more than $1{\times}10^2\;TCID_{50}/0.1ml$ of EMCV-CBNU showed symptoms of hind limb paralysis and eventually died during 3 and 8 days postinoculation (DPI). Furthermore, when we inoculated the virus into pregnant mice, all dams and their fetuses died in 6 DPI. This is the first report on a full genomic analysis of swine EMCV in Korea, which exhibits high virulence in mice.

• Journal of Microbiology and Biotechnology
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• v.25 no.3
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• pp.343-352
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• 2015

H9 is an ethanol extract prepared from nine traditional/medicinal herbs. This study was focused on the anticancer effect of H9 in non-small-cell lung cancer cells. The effects of H9 on cell viability, apoptosis, mitochondrial membrane potential (MMP; ${\Delta}\psi_{m}$), and apoptosisrelated protein expression were investigated in A549 human lung cancer cells. In this study, H9-induced apoptosis was confirmed by propidium iodide staining, expression levels of mRNA were determined by reverse transcriptase polymerase chain reaction, protein expression levels were checked by western blot analysis, and MMP (${\Delta}\psi_{m}$) was measured by JC-1 staining. Our results indicated that H9 decreased the viability of A549 cells and induced cell morphological changes in a dose-dependent manner. H9 also altered expression levels of molecules involved in the intrinsic signaling pathway. H9 inhibited Bcl-xL expression, whereas Bax expression was enhanced and cytochrome C was released. Furthermore, H9 treatment led to the activation of caspase-3/caspase-9 and proteolytic cleavage of poly(ADP-ribose) polymerase; the MMP was collapsed by H9. However, the expression levels of extrinsic pathway molecules such as Fas/FasL, TRAIL/TRAIL-R, DR5, and Fas-associated death receptor were downregulated by H9. These results indicated that H9 inhibited proliferation and induced apoptosis by activating intrinsic pathways but not extrinsic pathways in human lung cancer cells. Our results suggest that H9 can be used as an alternative remedy for human non-small-cell lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4209-4214
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• 2013

Background: Breast cancer is among the five most common cancers and ranks first among cancers diagnosed in Iranian women. Screening and treatment of this disease with molecular methods, especially regarding high incidences at early age and advanced stage, is essential. Several genes with altered expression have been identified by cDNA microarray studies in breast cancer, with the Bcl-2 gene indicated as a likely candidate. In this study, we studied Bcl-2 gene expression levels in parallel tumor and non-tumor breast tissues. Materials and Methods: Forty samples including 21 tumor, 16 non tumor (marginal) and 3 benign breast tissues which were all pathologically diagnosed, were subjected to RNA extraction and polyA RT-PCR with the expression level of Bcl-2 quantified using real-time PCR. Results: There is higher expression levels of the Bcl-2 gene in tumor samples compared with marginal samples, but not attaining significance(p>0.05). Bcl-2 expression in 14 (66.7%) of the cases of tumor samples and 9 (56.3%) cases of the marginal samples were positive. Comparison of the expression of the Bcl-2 gene in histological grade showed that a high expression of Bcl-2 was associated with a high histological grade (p<0.41). Conclusions: Our data suggests that dysregulated Bcl-2 gene expression is potentially involved in the pathogenesis of breast cancer. Using gene expression analysis may significantly improve our ability for screening cancer patients and will prove a powerful tool in the diagnosis and prognostic evaluation of the disease whilst aiding the cooperative group trials in the Bcl-2 based therapy project.

• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.4
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• pp.511-518
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• 2012

The mechanisms of Toll-like receptor (TLR) signaling have been the focus of extensive studies because TLRs are the target of therapeutic intervention on multiple diseases. In this study, we investigated the inhibitory potential of Vigna angularis (azuki bean) on the TLR signaling. The effect of Vigna angularis extract (JSD) on TLR activation was investigated by assessing NF-${\kappa}B$ and AP-1 inducible secreted embryonic alkaline phosphatase (SEAP) activity. JSD significantly inhibited SEAP activity induced by poly I:C (TLR3 ligand) and poly I (TLR7 ligand) in a dose-dependent manner at concentration below 100 ${\mu}g/ml$ with no sign of cytotoxicity. Pretreatment of JSD markedly suppressed mRNA expressions of pro-inflammatory cytokines and adhesive molecules such as TNF-${\alpha}$, IL-6, RANTES, MCP-1 and ICAM-1 induced by TLR ligands. It also diminished the phosphorylation of $I{\kappa}B$ kinase and $I{\kappa}B$, and followed by $I{\kappa}B$-mediated nuclear translocation of p50, p65, and phosphorylation of p38, JNK, and IRF signaling pathway. In conclusion, our results suggest that Vigna angularis has inhibitory activity on TLR-3 and -7 signaling and it can be further developed as a remedy in curing TLR-related multiple diseases.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.6
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• pp.391-397
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• 2010

E2F transcription factors and their target genes have been known to play an important role in cell growth control. We found that curcumin, a polyphenolic phytochemical isolated from the plant Curcuma longa, markedly suppressed E2F4 expression in HCT116 colon cancer cells. Hydrogen peroxide was also found to decrease E2F4 protein level, indicating the involvement of reactive oxygen species (ROS) in curucmin-induced downregulation of E2F4 expression. Involvement of ROS in E2F4 downregulation in response to curcumin was confirmed by the result that pretreatment of cells with N-acetylcystein (NAC) before exposure of curcumin almost completely blocked the reduction of E2F4 expression at the protein as well as mRNA level. Anti-proliferative effect of curcumin was also suppressed by NAC which is consistent to previous reports showing curcumin-superoxide production and induction of poly (ADP-ribose) polymerase (PARP) cleavage as well as apoptosis. Expression of several genes, cyclin A, p21, and p27, which has been shown to be regulated in E2F4-dependent manner and involved in the cell cycle progression was also affected by curcumin. Moreover, decreased (cyclin A) and increased (p21 and p27) expression of these E2F4 downstream genes by curcumin was restored by pretreatment of cells with NAC and E2F4 overexpression which is induced by doxycycline. In addition, E2F4 overexpression was observed to partially ameliorate curcumin-induced growth inhibition by cell viability assay. Taken together, we found curcumin-induced ROS down-regulation of E2F4 expression and modulation of E2F4 target genes which finally lead to the apoptotic cell death in HCT116 colon cancer cells, suggesting that E2F4 appears to be a novel determinant of curcumin-induced cytotoxicity.