• Tuberculosis and Respiratory Diseases
• /
• v.62 no.1
• /
• pp.33-42
• /
• 2007

Background: Heme oxygenase-1 (HO-1) is known to modulates the cellular functions, including cell proliferation and apoptosis. It is known that a high level of HO-1 expression is found in many tumors, and HO-1 plays an important role in rapid tumor growth on account of its antioxidant and antiapoptotic effects. Cisplatin is a widely used anti-cancer agent for the treatment of lung cancer. However, the development of resistance to cisplatin is a major obstacle to its use in clinical treatment. We previously demonstrated that inhibiting HO-1 expression through the transcriptional activation of Nrf2 induces apoptosis in A549 cells. The aim of this study was to determine of the inhibiting HO-1 enhance the chemosensitivity of A549 cells to cisplatin. Materials and Methods: The human lung cancer cell line, A549, was treated cisplatin, and the cell viability was measured by a MTT assay. The change in HO-1, Nrf2, and MAPK expression after the cisplatin treatment was examined by Western blotting. HO-1 inhibition was suppressed by ZnPP, which is a specific pharmacologic inhibitor of HO activity, and small interfering RNA (siRNA). Flow cytometry analysis and Western blot were performed in to determine the level of apoptosis. The level of hydrogen peroxide ($H_2O_2$) generation was monitored fluoimetrically using 2',7'-dichlorofluorescein diacetate. Results: The A549 cells showed more resistance to the cisplatin treatment than the other cell lines examined, whereas cisplatin increased the expression of HO-1 and Nrf2, as well as the phosphorylation of MAPK in a time-dependent fashion. Inhibitors of the MAPK pathway blocked the induction of HO-1 and Nrf2 by the cisplatin treatment in A549 cells. In addition, the cisplatin-treated A549 cells transfected with dither the HO-1 small interfering RNA (siRNA) or ZnPP, specific HO-1 inhibitor, showed in a more significantly decrease in viability than the cisplatin-only-treated group. The combination treatment of ZnPP and cisplatin caused in a marked increase in the ROS generation and a decrease in the HO-1 expression. Conclusion: Cisplatin increases the expression of HO-1, probably through the MAPK-Nrf2 pathway, and the inhibition of HO-1 enhances the chemosensitivity of A549 cells to cisplatin.

• Journal of Life Science
• /
• v.25 no.7
• /
• pp.801-809
• /
• 2015

Homotypic cell adhesion (homotypic aggregation) in activated monocytes plays a central role in physiological and pathological processes including inflammatory responses, differentiation and migration. The extract of the Prunus mume Sieb. et Zucc. fruit (Maesil) has potential benefits to human health; such as anti-viral, anti-microbial, and anti-cancer activities. Indeed, Maesil extract may modulate inflammatory responses via interference with homotypic aggregation in monocytes. In the present study, the molecular mechanisms underpinning the therapeutic efficacy of Maesil extract in inflammatory diseases were investigated. It was found that Maesil extract inhibited homotypic aggregation in lipopolysaccharide (LPS)-activated monocytes. This was mediated by reduction of nitric oxide (NO) production, partly via inhibition of inducible nitric oxide synthase (iNOS) expression in LPS-activated THP-1 cells. It was confirmed that NO inhibition is a key mechanism in Maesil induced blockade of monocyte aggregation through identification of reversal of this inhibitory effect by the NO-producing agent S-nitroso-N-acetyl penicillamine (SNAP). In addition, Maesil extract significantly attenuated LPS-induced IκB-α phosphorylation and NF-κB translocation into the nucleus. In conclusion, Maesil extract exerts anti-inflammatory effects via inhibition of homotypic aggregation of LPS-activated monocytes through mechanisms involving the suppression of NO production and NF-κB activity, suggesting Maesil extract as a potential therapeutic candidate for the prevention and treatment of chronic inflammatory diseases.

• Molecules and Cells
• /
• v.37 no.2
• /
• pp.178-186
• /
• 2014

Differential transcription of the clusterin (CLU) gene yields two CLU isoforms, a nuclear form (nCLU) and a secretory form (sCLU), which play crucial roles in prostate tumorigenesis. Pro-apoptotic nCLU and anti-apoptotic sCLU have opposite effects and are differentially expressed in normal and cancer cells; however, their regulatory mechanisms at the transcriptional level are not yet known. Here, we examined the transcriptional regulation of nCLU in response to hypoxia. We identified three putative hypoxia response elements (HREs) in the human CLU promoter between positions -806 and +51 bp. Using a luciferase reporter, electrophoretic gel mobility shift, and chromatin immunoprecipitation assays, we further showed that hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) bound directly to these sites and activated transcription. Exposure to the hypoxia-mimetic compound $CoCl_2$, incubation under 1% $O_2$ conditions, or overexpression of HIF-$1{\alpha}$ enhanced nCLU expression and induced apoptosis in human prostate cancer PC3M cells. However, LNCaP prostate cancer cells were resistant to hypoxia-induced cell death. Methylation-specific PCR analysis revealed that the CLU promoter in PC3M cells was not methylated; in contrast, the CLU promoter in LNCap cells was methylated. Co-treatment of LNCaP cells with $CoCl_2$ and a demethylating agent promoted apoptotic cell death through the induction of nCLU. We conclude that nCLU expression is regulated by direct binding of HIF-$1{\alpha}$ to HRE sites and is epigenetically controlled by methylation of its promoter region.

• Journal of Life Science
• /
• v.25 no.12
• /
• pp.1384-1392
• /
• 2015

Sagantang (SGT), a Korean multiherb formula comprising six medicinal herbs, Paeonia lactiflora Pall., Belamcanda chinensis (L.) DC, Gardenia jasminoides Ellis, Poria cocos Wolf, Cimicifuga heracleifolia Komarov, and Artractylodes japonica Koidzumi, was recorded in “Dongeuibogam.” The present study investigated the anticancer potential of SGT in AGS human gastric carcinoma cells. The results indicated that SGT treatment significantly inhibited the growth and viability of AGS cells in a dose-dependent manner, which was associated with the induction of apoptotic cell death, as evidenced by the formation of apoptotic bodies, in addition to chromatin condensation and DNA fragmentation, and the accumulation of annexin-V positive cells. The induction of apoptotic cell death by the SGT treatment was associated with up-regulation of Fas protein expression, truncation of Bid, and down-regulation of the anti-apoptotic Bcl-2 protein. The SGT treatment also effectively induced the loss of mitochondrial membrane potential, which was associated with the activation of caspases (caspase-3, -8, and -9) and degradation of poly (ADP-ribose) polymerase. However, a pan-caspase inhibitor significantly blocked the SGT-induced apoptosis and growth suppression in AGS cells. This study suggests that SGT induces caspase-dependent apoptosis through an extrinsic pathway by upregulating Fas, as well as through an intrinsic pathway by modulating Bcl-2 family members in AGS cells. The results suggest that SGT may be a potential chemotherapeutic agent for the control of human gastric cancer cells. However, further studies will be needed to confirm the potential of SGT in cancer prevention and therapy in an in vivo model and to identify biological active compounds of SGT.

• Microbiology and Biotechnology Letters
• /
• v.37 no.2
• /
• pp.170-175
• /
• 2009

The extract of Platycarya strobilacea is known to possess a wide range of pharmacological activities including anti-inflammatory, anti-fungal, and anti-cancer properties. We have reported that the ethyl acetate fraction of Platycarya strobilacea (PS-ET fraction) has high potential as an antioxidant agent (J. Soc. Cosmet. Scientists Korea 34(4) 275, 2008). In this study, antibacterial activity of the fraction and stability of the cream containing 0.2% PS-ET fraction were investigated for the application to cosmetics. Antibacterial activity of PS-ET fraction against various skin pathogenic bacteria (Propionibacterium acnes, Staphylococcus aureus, and Pityrosporum ovale) was measured by minimum inhibitory concentration (MIC). MIC values of PS-ET fraction on P. acnes, S. aureus, and P. ovale were 0.13%, 0.06% and 0.25%, respectively. The results showed that the antibacterial activity of the fraction was the highest in the S. aureus. For the stability evaluation, pH and viscosity of the cream containing 0.2% PS-ET fraction were measured. The results showed that pH changes of the cream containing PS-ET fraction was lower than the control cream without PS-ET fraction. And the PS-ET fraction could repress the decrease of viscosity of the cream against sunlight treatment. These results suggest that the fraction of Platycarya strobilacea has high potential as bactericide against the skin pathogenic bacteria and could be added to improve the stability of cosmetic products.

• The Korean Journal of Pesticide Science
• /
• v.19 no.4
• /
• pp.354-360
• /
• 2015

In recent years, Allium victorialis has been extensively used as a pharmacological agent for various diseases in the form of anti-arteriosclerotic, anti-diabetic and anti-cancer. Allium victorialis is severely affected by various fungal diseases since it naturally grow in the shady and humid environments in Korea. In this case, different types of fungicides are applied to control the fungal diseases in Allium victorialis. The present study was aimed to determine the residual characteristics of two fungicides namely tebuconazole and fludioxonil on Allium victorialis. For this study, the fungicides were drenched soil on Allium victorialis in the cultivation area Pyeongchang by the standard (two thousand fold) and double (thousand fold) dilutions. At the end of $15^{th}$, $30^{th}$ and $40^{th}$ days samples were collected for residue analysis. Residues of tebuconazole and fludioxonil were analyzed using GC/NPD (Gas Chromatography/Nitrogen Phosphorus Detector) and their recovery were found to be 108.8~119.5% and 91.3~104.8%, respectively. The method of limits of quantification for both fungicides was $0.01mg\;kg^{-1}$. Further, the results of this study shows that the residue levels of both fungicides on Allium victorialis were <$0.01{\sim}0.12mg\;kg^{-1}$ and $0.01{\sim}0.09mg\;kg^{-1}$ and their % ADI (% Acceptable Daily Intake) were 17.44% and 25.75%, respectively. Based on the results obtained in this study, we suggest that the residue levels of both of the fungicides on Allium victorialis are safe and these fungicides can also be used to control fungal diseases in Allium victorialis.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.44 no.4
• /
• pp.592-601
• /
• 2015

Rubus coreanus is known as Korean black raspberry, native to Korea, Japan, and China. Preliminary studies evaluating their potential for cancer treatment in mammalian test systems are ongoing. In recent years, interest has been renewed due to their high levels of anthocyanins. Anthocyanins in black raspberry are important due to their potential health benefits as dietary antioxidant, anti-inflammatory compound, and as a chemopreventive agent. In the present study, Saccharomyces cerevisiae BA29 was isolated from black raspberry fruit and fruit juice as a biogenic amine non-producing strain for manufacturing of black raspberry wine, after which we investigated its characteristics: biogenic amine-producing ability, cell growth ability, alcohol-fermentation ability, and resistance to alcohol, glucose, and sulfur dioxide. Based on preliminary experiments, we optimized culture medium compositions for improving dried cell weight of S. cerevisiae BA29 by response surface methodology (RSM) as a statistical method. Design for RSM used a central composite design, and molasses with the industrial applicability was used as a carbon source. Through statistical analysis, we obtained optimum values as follows: molasses 200 g/L, peptone 30 g/L, and yeast extract 40 g/L. For the model verification, we confirmed about 3-fold improvement of dried cell weight from 6.39 to 20.9167 g/L compared to basal yeast peptone dextrose medium. Finally, we manufactured black raspberry wine using S. cerevisiae BA29 and produced alcohol of 20.33%. In conclusion, S. cerevisiae isolated from black raspberry fruit and juices has a great potential in the fermentation of black raspberry wine.

• Korean Journal of Clinical Laboratory Science
• /
• v.50 no.3
• /
• pp.337-344
• /
• 2018

Hepatocellular carcinoma (HCC), a major type of hepatoma, is associated with high recurrence and mortality because of its uncontrolled metastatic feature. Silymarin is a polyphenolic flavonoid from Silybum marianun (milk thistle) and exhibits anti-carcinogenic activity through modulation of the epithelial-mesenchymal transition (EMT) in several cancer cells. In this study, the inhibitory mechanism of silymarin against migration and invasion was investigated in the Huh7 HCC cell line. Wound healing and in vitro invasion assays were conducted to examine the effects of silymarin on migration and invasion. Western blot analysis was also applied to evaluate the inhibitory effects of silymarin on the EMT-related genes and their upstream signaling molecules. Silymarin inhibited the migratory and invasive activities of Huh7 cells. In addition, silymarin attenuated the protein expression levels of vimentin and matrix metalloproteinase (MMP)-9 as well as their transcription factors, Snail, and nuclear factor $(NF)-{\kappa}B$, while the expression of E-cadherin was increased by the silymarin treatment. Among the upstream signaling molecules, the phosphorylation of Akt was inhibited by the silymarin treatment, which was confirmed by the selective inhibitor, LY294002. Consequently, silymarin inhibited the invasive and migratory activities in Huh7 cells through the modulation of EMT-related gene expression by the PI3K/Akt signaling pathway, which may have potential as a chemopreventive agent against HCC metastasis.

• The Korea Journal of Herbology
• /
• v.21 no.2
• /
• pp.37-46
• /
• 2006

Objectives : The purpose of this study was to investigate the effect of Dangguibohyultang (DB) and its combination (DB-I; Astragali membraneus BUNGE : Angelica gigas NAKAI=5:1, DB-II; Astragali membraneus BUNGE:Angelica gigas NAKAI=1:1, DB-III; Astragali membraneus BUNGE:Angelica gigas NAKAI=1:5,) on apoptosis in human colorectal adenocarcinoma HCT116 cells. Methods : To study the cytotoxic effect of methanol extract of DB-I, DB-II and DB-III on HCT116 cells, the cell viability was determined by XTT reduction method and ttypan blue exclusion assay. To confirm the induction of apoptosis, the cleavage of poly ADP-ribose polymerase (PARP), a substrate for caspase-3 and a typical sign of apoptosis, and the activation of procaspase-3, -8 and -9 were examined by western blot analysis. Furthermore, DB-induced apoptosis was confirmed by DNA fragmentation. The release of cytochrome C from mitochondria to cytosol, the level of Bcl-2 and Bax, and the expressions of Raf/MEK/ERK were examined by western blot analysis. Results : DB-I and DB-II reduced proliferation of HCT116 cells in a dose-dependent manner. DB-I and DB-II decreased procaspase-3, -8, -9 levels in a dose-dependent manner and induced the clevage of PARP. DB-I and DB-II also triggered the mitochondrial apoptotic signaling by increasing the release of cytochrome C from mitochondria to cytosol, decreasing of anti-apoptotic Bcl-2, and increasing of pro-apoptotic Bax. DB-I and DB-II decreased the activation of Ras/Raf/MEK/ERK cascade in a dose-dependent manner. Conclusion : These results suggest that DB-I and DB-II induce apoptosis via mitochondrial pathway in HCT116 cells. Furthermore, Raf/MEK/ERK cascade is involved in DB-induced apoptosis. These results suggest that DB is potentially useful as a chemotherapeutic agent in human liver cancer.

• Archives of Pharmacal Research
• /
• v.25 no.5
• /
• pp.655-663
• /
• 2002

Liver fibrosis is a prepathological state wherein damaged liver tissues in chronic liver diseases, such as hepatitis, are not repaired to normal tissues, but converted to fibrous tissue. 5-(2-Pyrazinyl)-4-methyl-1,2-dithiol-3-thione (oltipraz), a cancer chemopreventive agent, is effective against a wide variety of chemical carcinogens. Recently, we reported that oltipraz inhibits liver fibrogenesis (Kang et al., 2002). In the present study, the effects of oltipraz in combination with dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate (DDb) on dimethylnitrosamine (DMN)-induced liver fibrogenesis were assessed in rats. Oltipraz (30 mg/kg body weight, po, 3 times per week for 4 weeks) was found to inhibit the increases in plasma ALT, AST and bilirubin by DMN, whereas DDB (30 mg/kg body weight, po, 3 times per week for 4 weeks) attenuated the increases in the plasma ALT and bilirubin. The lowered plasma protein and albumin contents in DMN-treated rats were completely restored by oltipraz, but not by DDB. DDB decreases liver cell injury and inflammation through inhibition of nuclear factor-kB. DMN increased the accumulation of liver collagen, as indicated by the increase in the 4-hydroxyproline content in liver homogenates, which was reduced by treatment with oltipraz, but not by DDB. Given the differential effect between oltipraz and DDB, the potential enhancement of antifibrotic efficacy by the drugs was assessed in the animal model. Despite the minimal effect of DDB on DMN-induced fibrogenesis, DDB (5-25 mg/kg), administered together with oltipraz (25-5 mg/kg), showed an additive protective effect against hepatotoxicity and fibrosis induced by DMN, which was shown by the blood chemistry parameters and histopathological analysis. The adequate composition ratio of oltipraz to DDB was 5:1. These results provide information on the pharmaceutical composition, comprising of oltipraz and DDB as the active components, for the treatment and/or prevention of liver fibrosis and cirrhosis.