• Food Science and Preservation
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• v.10 no.3
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• pp.394-400
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• 2003

This study was earned out to investigate the antimutagenic and cytotoxic effects of Eleutherococcus senticosus Maxim fruits ethanol extract on Salmonella typhimurium TA98, TA100 and cancer cell lines using Ames test and SRB assay, respectively. They were extracted with ethanol and then fractionated with hexane, chloroform, ethyl acetate, butanol and water to get active fractions. In the Ames test, most of the extracts had strong antimutagenic effects against the mutagenesis induced by MNNG, 4NQO, B(${\alpha}$)P and Trp-P-l. The ethanol extract (200 $\mu\textrm{g}$/plate) of Eleutherococcus senticosus fruits showed 87.2％ inhibitory effect on the mutagenesis induced by MNNG against TA100. And also, The suppression ratio against B(${\alpha}$)P and Trp-P-l in the TA100 showed 96.1％ and 95.5％, respectively. In the cytotoxic effects against human cancer cell lines (A549, AGS, MCF-7, Hep3B), the value of inhibition were mostly above 60％ for each fraction (1 mg/mL). Hexane fraction (1 mg/mL) against showed the strongest cytotoxic effects of 92.7％ compared to those of other fraction and butano fraetion against Hep3B was relatively high growth inhibitory effect of 82％.

• Korean Journal of Medicinal Crop Science
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• v.13 no.4
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• pp.199-205
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• 2005

This study was carried out to investigate the effect of 70% ethanol extract and each fraction from Rhododendron brachycarpum D. Don leaves on cytotoxicity, anticancer, genotoxicity and immunological activity in vitro bioassay. Cytotoxicity for human normal cells (HEL299 and Chang) of the samples was shown below 35% in 0.5 mg/ml concentration of samples except aqueous fraction by SRB assay. DNA damage on the Chang cell of the samples alone in comet assay was observed very weak damage activity even in high concentration (1 mg/ml) of the samples. The anticancer effect of the samples on human cancer cell lines (A549, AGS, Hep3B, MCF7) was indicated that the cancer cells were inhibited gradually in proportion to the increase of the concentration of the samples by MTT assay. The growth of the Raji and Jurkat cells were hastened by adding butanol fraction among the samples. In the genotoxicity on $H_2O_2-induced$ DNA damage in Chang cells using alkaline comet assay, most of samples were shown a strong protective activity from DNA OTM values.

• Journal of Korean Society of Forest Science
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• v.98 no.4
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• pp.399-408
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• 2009

We investigated the improvement of immuno-modulatory activities of sap of Acer mono and A. okamotoanum encapsulated with edible polymers. Anticancer activities and immune activities such as human B and T cell growth, secretion of cytokines and natural killer cell growth were observed. Both human immune B and T cells were increased up to 30~50% by the addition of nano particle sap of Acer mono and A. okamotoanum. The secretion of Interleukin-6 (IL-6) and Tumor necrosis factor-a (TNF-a) from human immune B and T cells were also significantly increased compare to the control. Natural Killer (NK) cell growth was enhanced to $19.4{\times}10^5$ cells/mL in adding nano encapsulated sap of A.okamotoanum. The cytotoxicity of the sample on normal human lung cell (HEL299) was below 19.8% in adding 1.0 mg/mL of the nano particle sap of A. okamotoanum. Generally, the growth of all three human lung adenocarcinoma, human stomach adenocarcinoma and human liver adenocarcinama was inhibited up to 85% in adding 1.0 mg/mL of the encapsulated sap. Interestingly enough, the encapsulated sap was completely penetrated into human cancer cells within 30 min after addition. It showed that the encapsulation of the sap definitely increased its biological activities, which can expand its use to wide range of food industries.

• Tuberculosis and Respiratory Diseases
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• v.57 no.5
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• pp.449-460
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• 2004

Background : PS-341 is a novel, highly selective and potent proteasome inhibitor, which showed cytotoxicity against some tumor cells. Its anti-tumor activity has been suggested to be associated with modulation of the expression of apoptosis-associated proteins, such as p53, $p21^{WAF/CIP1}$, $p27^{KIP1}$, NF-${\kappa}B$, Bax and Bcl-2. c-Jun N-terminal kinase (JNK) and glycogen synthase kinase-$3{\beta}$ (GSK-$3{\beta}$) are important modulators of apoptosis. However, their role in PS-341-induced apoptosis is unclear. This study was undertaken to elucidate the role of JNK and GSK-$3{\beta}$ in the PS-341-induced apoptosis in lung cancer cells. Method : NCI-H157 and A549 cells were used in the experiments. The cell viability was assayed using the MTT assay and apoptosis was evaluated by proteolysis of PARP. The JNK activity was measured by an in vitro immuno complex kinase assay and by phosphorylation of endogenous c-Jun. The protein expression was evaluated by Western blot analysis. Dominant negative JNK1 (DN-JNK1) and GSK-$3{\beta}$ were overexpressed using plasmid and adenovirus vectors, respectively. Result : PS-341 reduced the cell viability via apoptosis, activated JNK and increased the c-Jun expression. Blocking of the JNK activation by overexpression of DN-JNK1, or pretreatment with SP600125, suppressed the apoptosis induced by PS-341. The activation of caspase 3 was mediated by JNK activation. Blocking of the caspase 3 activation suppressed PS-341-induced apoptosis. PS-341 activated the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, but its blockade enhanced the PS-341-induced cell death via apoptosis. GSK-$3{\beta}$ was inactivated by PS-341 via the PI3K/Akt pathway. Overexpression of constitutively active GSK-$3{\beta}$ enhanced PS-341-induced apoptosis; in contrast, this was suppressed by dominant negative GSK-$3{\beta}$ (DN-GSK-$3{\beta}$). Inactivation of GSK-$3{\beta}$ by pretreatment with lithium chloride or the overexpression of DN-GSK-$3{\beta}$ suppressed both the JNK activation and c-Jun up-regulation induced by PS-341. Conclusion : The JNK/caspase pathway is involved in PS-341-induced apoptosis, which is negatively regulated by the PI3K/Akt-mediated inactivation of GSK-$3{\beta}$ in lung cancer cells.

• 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.

• Tuberculosis and Respiratory Diseases
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• v.54 no.4
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• pp.449-458
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• 2003

Background : Cyclosporin A(CsA) and tacrolimus(FK506) have been widely used as immunosuppressants. The effects of CsA, or FK506, on the $I{\kappa}B/NF-{\kappa}B$ pathway have been shown to vary according to the cell type. However, their effects on the $I{\kappa}B/NF-{\kappa}B$ pathway have not been reported in bronchial epithelial cells. In this study, the effects of CsA and FK506 on the $I{\kappa}B/NF-{\kappa}B$ pathway in bronchial epithelial cells, monocytes, lymphocytes and alveolar macrophages were evaluated. The relationship between their effects on the $I{\kappa}B/NF-{\kappa}B$ pathway and $I{\kappa}B$ kinase(IKK) activity was also investigated. Methods : BEAS-2B and A549 cells, pulmonary alveolar macrophages, peripheral blood monocytes and lymphocytes were used. The cells were pre-treated with CsA, or FK506, for various time periods, followed by stimulation with TNF-${\alpha}$, LPS or IL-$1{\beta}$. The $I{\kappa}B{\alpha}$ expressions were assayed by Western blot analyses. The IKK activity was evaluated by an in vitro immune complex kinase assay, using GST-$I{\kappa}B{\alpha}$ as the substrate. Results : Neither CsA nor FK506 affected the level of $I{\kappa}B{\alpha}$ expression in any of the cell types used in this study. CsA pre-treatment inhibited the TNF ${\alpha}$-induced $I{\kappa}B{\alpha}$ degradation in bronchial epithelial cells. In contrast, the TNF ${\alpha}$-induced $I{\kappa}B{\alpha}$ degradation was not affected by FK506 pre-treatment. However, FK506 suppressed the cytokine-induced $I{\kappa}B{\alpha}$ degradation in the pulmonary alveolar macrophages, peripheral blood monocytes and lymphocytes. The inhibitory effect of CsA, or FK506, on $I{\kappa}B{\alpha}$ degradation was not related to IKK. Conclusions : CsA and FK506 suppressed the $I{\kappa}B{\alpha}$ degradation in bronchial epithelial cells, monocytes, lymphocytes and alveolar macrophages, so this may not be mediated through IKK.

• Food Science of Animal Resources
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• v.23 no.2
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• pp.172-179
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• 2003

This study was carried out to find the preventive medical and therapeutic effects of Sarcodon asparatus on adult disease by employing several biological and biochemical assays. Nitrate scavenging ability(NSA) of Sarcodan asparatus extracts was displayed up to 99.9% at pH 1.2 in a dose-dependent manner. They also had 90.4% electron donating ability(EDA) at the concentration of 0.1 mg/mL. Extracts of Sarcodon asparatus were also able to function as a powerful antioxidant at all concentrations(0.01∼l.0 mg/mL). Furthermore, we observed that 1 mg/mL concentration of the extracts was more powerful than BHT, With respect to fibrolytic activity, Sarcodon asparatus showed 1,843.8 unit/g, which was higher than streptokinase(1,189 unit/g). The inhibitory effects of the extracts on angiotensin converting enzyme, measured by the normal and pretreatment methods, were 53 and 58%, respectively. We also performed cytotoxicity effect of Sarcodon asparatus extracts on a various cancer cell lines. The growth inhibitory effects of the extracts(5.0 mg/mL) on A549, HeLa, AGS, and SK-Hep-1 cells were 78.9, 55.3, 69.0, and 42.5 %, respectively. Interestingly, Sarcodon asparatusextracts induced mutation on Salmonella typhimurium TA98 and TA100 when Ames test was done.

• Food Science and Preservation
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• v.31 no.4
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• pp.673-681
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• 2024

This study was conducted to develop kombucha with better functionality. The developed kombucha (CK) was prepared using the sugar extracts from fruits of Cudrania tricuspidata (Carrière) Bureau ex Lavallée instead of the sugar, which is used as a substrate for SCOBY in conventional kombucha (K). During fermentation, the soluble solids content significantly decreased in CK compared to K, and the pH change decreased rapidly in CK compared to K. On the 14^th day of fermentation, the weight of the SCOBY in CK was higher than that in K. Immediately after preparation, K contained only sucrose, but CK contained sucrose, glucose, and fructose. SCOBY appears to use glucose and fructose preferentially during fermentation. K contained acetic acid and citric acid right after preparation. However, as fermentation progressed, the composition changed to acetic acid, citric acid, and lactic acid. At the same time, CK initially consisted of citric acid, lactic acid, and acetic acid. However, acetic acid and citric acid increased but lactic acid decreased significantly on the 14^th day of fermentation. In the cytotoxicity studies, the CK showed a proliferation-promoting effect on normal lung cells (MRC-5) and strong cytotoxicity against human lung cancer cells (A549). These results suggest that the kombucha made from sugar extracts of C. tricuspidata fruits can be used as a more functional beverage than regular kombucha.

• The Korean Journal of Nuclear Medicine
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• v.35 no.3
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• pp.168-184
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• 2001

Purpose: KR-30035 (KR), a new MDR reversing agent, has been found to produce a similar degree of increased Tc-99m MIBI uptake in cultured tumor cells over-expressing mdr1 mRNA compared to verapamil (VP), with less cardiovascular effects. We assessed the MDR-reversing ability of KR in vivo, and effects of various doses of KR on MIBI uptake un nude mice hearing P-glycoprotein (P-gp) positive (+) and P-gp negative (-) human tumor xenografts. Methods: P-gp (+) HCT15/CL02 colorectal and P-gp (-) A549 non-small cell cancer cells were inoculated in each flank of 120 nude mice (20 mice ${\times}$ 6 groups). Group 1 (Gr1) mice received 10mg/kg KR i.p. 3 times $({\times}3)$; Gr2, 10mg/kg VP i.p. ${\times}3$; Gr3, 10mg/kg KR i.p. ${\times}2$ + 25mg/kg KR i.p. ${\times}1$; Gr4, 10mg/kg KR i.p. ${\times}2$ + 50mg/kg i.p. ${\times}1$; Gr5, 10mg/kg KR i.p. ${\times}2$ + 25mg/kg KR i.v. ${\times}1$, GrC, controls. The mice were then injected with Tc-99m MIBI and sacrificed after 10 min, 30 min, 90 min and 240 min. Tumor uptake of MIBI (TU) in each group was compared. Results: TU in P-gp (+) and (-) tumors were both higher in Gr1 than Gr2. Washout rate between the 10 min and 4 hours was lower in Gr5 of P-gp (+) cell(0.93) than the control. Percentage increases in TU were higher in P-gp (+) than P-gp (-) tumors with all KR doses. Pgp (+) TU were highest at 10 mon (173% of GrC) and persisted up to 240 min (144%) in Gr3. Larger doses of KR resulted in a lesser degree of increase in P-gp (+) TU at 10 min (130% in Gr4 and 117% un Gr5) and 30 min (178%, 129%), but TU increased by time up to 240 min (177%, 196%). Heart and lung uptakes were markedly increased in Gr4 and Gr5 at 10 and 30 min, likely due to cardiovascular effects. No mice died. Conclusion: These data further suggest that KR that has significantly lower cardiovascular toxicity than verapamil can be used as an active inhibitor of MDR. Even a relatively low dose of KR significantly increased Tc-99m MIBI uptake in P-gp (+) tumors in vivo.

• The Journal of Internal Korean Medicine
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• v.27 no.2
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• pp.429-443
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• 2006

Objectives : The Purpose of this study was to identify anti-tumor effects of Curcuma longa L. on some kinds of cancer cells through molecular biologic methods. Materials & Methods : We used 4 kinds of cancer cell lines such as glioma cells(A172), cervical cancer cells(HeLa), Prostate cancer cells(PC3), lung cancer cells(A549). We injected the boiled extract of Curcuma longa L. $5{\mu}g,\;10{\mu}g$ to culture media(ml) for 24 hours. We measured the cytotoxic effect on 4 kinds of cancer cells through trypan blue exclusion test and the suppressive effect on viability of 4 kinds of cancer cells via MTT assay. We measured the change of mitochondria membrane potential via flow cytometry. The quantitative RT-PCR was used to examine the effect on the revelation of Bcl-2 and Bax which genes are related to apoptosis. We examined the effect on the revelation of Bcl-2 protein and Bax protein by western blot analysis. Results: 1. Extract of Curcuma longa L. showed significant cytotoxic effect on A172, HeLa, PC3 compared to the control group with density dependent manner. 2. Extract of Curcuma longs L. showed significant suppressive effect on viability of A172, HeLa, PC3 compared to the control group with density dependent manner. 3. Curcuma longs L. induced apoptosis by decreasing the membrane potential of mitochondria in A172, HeLa, PC3. 4. In the test about the revelation of genes related to apoptosis, the revelation of Bcl-2 decreased and the revelation of Bax increased in A172. HeLa, PC3 treated with Curcuma longa L. with density dependent manner. 5. In the test about the revelation of protein related to apoptosis, the protein levels of Bcl-2 decreased and the protein levels of Bax increased in A172, HeLa, PC3 treated with Curcuma longa L. Conclusions: This experiment shewed that Curcuma longs L. has anti-tumor effect on glioma, cervical, Prostate cancer cells except on lung cancer. We hope that anti-tumor effects of Curcuma longa L. will be more Practically identified.