An Arylnaphthalene Lignan Daurinol Inhibits Cell Proliferation through Control of Wnt Signaling in Human Colorectal Carcinoma Cells

Saet Byoul Lee,Ji Hye Yoo,Kyung Su Kang,Dulamjav Batsuren,Joo Young Lee,Cheol Ho Pan,Chu Won Nho 한국응용생명화학회 2008 Applied Biological Chemistry (Appl Biol Chem) Vol.51 No.5

Cancer Chemopreventive Effects of Korean Seaweed Extracts

Saet Byoul Lee,Joo Young Lee,Dae-Geun Song,Cheol-Ho Pan,Chu Won Nho,Min Cheol Kim,Eun Ha Lee,Sang Hoon Jung,Hyung-Seop Kim,Yeong Shik Kim,Byung Hun Um 한국식품과학회 2008 Food Science and Biotechnology Vol.17 No.3

Cancer chemopreventive effects can be exerted through the induction of phase II detoxification enzymes and the inhibition of inflammatory responses. In this study, the cancer chemopreventive effects and anti-inflammatory responses of 30 seaweed extracts were examined. The extracts of Dictyota coriacea and Cutleria cylindrica exhibited the high chemoprevention index, having 4.36 and 4.66, respectively. They also activated antioxidant response element at 100 μg/mL by about 3-fold while did not activate xenobiotic response element. Seven seaweed extracts, Ishige okamurae, Desmarestia ligulata, Desmarestia viridis, Dictyopteris divaricata, D. coriacea, Sargassum horneri, and Sargassum yezoense, showed significant inhibition on nitric oxide (NO) and prostaglandin E₂ (PGE₂) production in a dose-dependant manner in 5-20 μg/mL. These seaweed extracts could be used as food materials for cancer chemoprevention. D. coriacea could contain potential chemopreventive agents not only that regulate genes via an ARE-dependent mechanism but also prevent the inflammation through inhibition of NO and PGE₂ production.

The Chemopreventive Effects of Carpesium abrotanoides Are Mediated by Induction of Phase II Detoxification Enzymes and Apoptosis in Human Colorectal Cancer Cells

Saet Byoul Lee,강경수,Hee Ju Lee,Ji Ho Yun,조은혜,김철영,Chu Won Nho 한국식품영양과학회 2010 Journal of medicinal food Vol.13 No.1

Cancer chemoprevention is thought to occur either by blocking the initiation of or suppressing the promotion of carcinogenesis. Phase II detoxification enzymes are known to play important roles in cancer chemoprevention because they enhance cytoprotection through detoxification and elimination of activated carcinogens at tumor initiation. Apoptosis is one of the most important inhibitory targets for tumor promotion. In this study, we have investigated the cancer chemopreventive activity of the ethanolic extract of Carpesium abrotanoides (CAE). We found that CAE induced quinone reductase [also known as NAD(P)H:quinone oxidoreductase (NQO1)] activity, increased NQO1 mRNA and protein expression, and had a relatively high chemoprevention index (12.04). CAE also significantly activated the antioxidant response element through the nuclear accumulation of NF-E2-related factor 2 in HCT116. Interestingly, we also found that CAE induced apoptosis, as evidenced by the externalization of phosphatidylserine, increased sub-G0/G1 content, chromatin condensation, poly(ADP-ribose) polymerase cleavage, and p53. These data suggest that the chemopreventive effects of C. abrotanoides can result from both the induction of phase II detoxification enzymes and from apoptosis. Thus, CAE could potentially be developed as a cancer chemopreventive agent for prevention or treatment of human cancers.

The Antimicrobial Activity of Essential Oil from Dracocephalum foetidum against Pathogenic Microorganisms

Saet Byoul Lee,Kwang Hyun Cha,김수남,Shataryn Altantsetseg,Sanduin Shatar,Oidovsambuu Sarangerel,Chu Won Nho 한국미생물학회 2007 The journal of microbiology Vol.45 No.1

A number of essential oils from Mongolian aromatic plants are claimed to have antimicrobial activities. The essential oil of Dracocephalum foetidum, a popular essential oil used in Mongolian traditional medicine, was examined for its antimicrobial activity. Eight human pathogenic microorganisms including B. subtilis, S. aureus, M. lutens, E. hirae, S. mutans, E. coli, C. albicans, and S. cerevisiae were examined. The essential oil of Dracocephalum foetidum exhibited strong antimicrobial activity against most of the pathogenic bacteria and yeast strains that were tested; by both the agar diffusion method and the minimum inhibitory concentration (MIC) assay (MIC range was 26-2592 μg/ml). Interestingly, Dracocephalum foetidum even showed antimicrobial activity against methicilin-resistant Staphylococcus aureus(MRSA) strains. We also analyzed the chemical composition of the oil by GC-MS and identified several major components, including n-Mentha-1,8-dien-10-al, limonene, geranial, and neral.

The Chemopreventive Effect of Taxifolin Is Exerted through ARE-Dependent Gene Regulation

Lee, Saet Byoul,Cha, Kwang Hyun,Selenge, Dangaa,Solongo, Amgalan,Nho, Chu Won Pharmaceutical Society of Japan 2007 Biological & pharmaceutical bulletin Vol.30 No.6

<P>Phase II detoxification enzymes are responsible for the detoxification and elimination of activated carcinogens, and thus act as important biomarkers for chemoprevention. In this study, we tested the chemopreventive activity of taxifolin, a flavanon compound purified from a mongolian medicinal plant, by measuring quinone reductase (QR) activity in HCT 116 cells. Taxifolin induced significant QR activity, but displayed relatively low cytotoxicity in cells (chemoprevention index=5.75). To identify the target genes regulated by taxifolin, DNA microarray was performed with a 3K human cancer chip containing 3096 human genes associated with carcinogenesis. Significant analysis of microarray (SAM) revealed 428 differentially expressed (DE) genes as statistically significant, with a false discovery rate (FDR) of 57.2% (delta=0.3366). Sixty-five genes, including a few detoxification enzymes (<I>NQO1</I>, <I>GSTM1</I>) and an antioxidant enzyme (<I>TXNRD1</I>), were up-regulated and 363 genes were down-regulated in the presence of 60 μ<SMALL>M</SMALL> taxifolin. In view of the finding that selected genes of interest contained antioxidant response element (ARE), we hypothesize that taxifolin modulates chemopreventive genes through activation of the ARE. Transient transfection experiments using the ARE QR-CAT construct demonstrate that taxifolin significantly activates ARE, but not xenobiotic response element (XRE). In conclusion, taxifolin acts as a potential chemopreventive agent by regulating genes <I>via</I> an ARE-dependent mechanism.</P>

The Antimicrobial Activity of Essential Oil from Dracocephalum foetidum against Pathogenic Microorganisms

Lee, Saet-Byoul,Cha, Kwang-Hyun,Kim, Su-Nam,Altantsetseg, Shataryn,Shatar, Sanduin,Sarangerel, Oidovsambuu,Nho, Chu-Won The Microbiological Society of Korea 2007 The journal of microbiology Vol.45 No.1

A number of essential oils from Mongolian aromatic plants are claimed to have antimicrobial activities. The essential oil of Dracocephalum foetidum, a popular essential oil used in Mongolian traditional medicine, was examined for its antimicrobial activity. Eight human pathogenic microorganisms including B. subtilis, S. aureus, M. lutens, E. hirae, S. mutans, E. coli, C. albicans, and S. cerevisiae were examined. The essential oil of Dracocephalum foetidum exhibited strong antimicrobial activity against most of the pathogenic bacteria and yeast strains that were tested; by both the agar diffusion method and the minimum inhibitory concentration (MIC) assay ($MIC\;range\;was\;26-2592{\mu}g/ml$). Interestingly, Dracocephalum foetidum even showed antimicrobial activity against methicilin-resistant Staphylococcus aureus (MRSA) strains. We also analyzed the chemical composition of the oil by GC-MS and identified several major components, including n-Mentha-1,8-dien-10-al, limonene, geranial, and neral.

The Chemopreventive Effects of <i>Saussurea salicifolia</i> through Induction of Apoptosis and Phase II Detoxification Enzyme

Kang, Kyungsu,Lee, Hee Ju,Kim, Chul Young,Lee, Saet Byoul,Tunsag, Jigjidsuren,Batsuren, Dulamjav,Nho, Chu Won Pharmaceutical Society of Japan 2007 BIOLOGICAL & PHARMACEUTICAL BULLETIN Vol.30 No.12

<P>The ethanol extract of the aerial part of the Mongolian medicinal plant <I>Saussurea salicifolia</I> induced a dose-dependent cell growth inhibition in both human gastric adenocarcinoma AGS cells and mouse hepatoma Hepa 1c1c7 cells (IC<SUB>50</SUB>=30.22 and 116.96 μg/ml), respectively. The extract induced an apoptosis in AGS cells inference from the externalization of the phosphatidylserine, the increase of the sub G0/G1 content (%) and the apoptotic morphological changes including membrane blebbing, the formation of apoptotic bodies and chromatin condensation. In order to identify active substances causing the apoptosis, we further isolated major compounds present in <I>Saussurea salicifolia</I> and 7 compounds were isolated including a sesquiterpene lactone, cynaropicrin, 3 lignans (trachelogenin, matairesinol and arctigenin) and 3 lignan glycosides (tracheloside, matairesinoside and arctiin). In general the lignan aglycones were more cytotoxic than their lignan glycosides in both AGS cells and Hepa 1c1c7 cells. Cynaropicrin not only showed the most potent cytotoxicity among the 7 major compounds but also it induced an apoptosis and a weak G2/M arrest in AGS cells. Arctigenin had the second-best cytotoxicity among 7 major compounds, and induced an apoptosis. In order to evaluate the induction of the phase II detoxification enzyme, we measured the induction of quinone reductase activity of the extract, fractions and compounds in Hepa 1c1c7 cells. The ethyl acetate fraction and arctigenin showed the strongest cancer chemopreventive activity (chemoprevention index=9.88 and 7.57, respectively). These data suggest that the extract as well as the lignan compounds (especially arctigenin) originated from <I>Saussurea salicifolia</I> may be served as potential cancer chemopreventive agents for prevention or treatment of human cancers.</P>

Tectoridin, a poor ligand of estrogen receptor α, exerts its estrogenic effects via an ERK-dependent pathway

Kang, Kyungsu,Lee, Saet Byoul,Jung, Sang Hoon,Cha, Kwang Hyun,Park, Woo Dong,Sohn, Young Chang,Nho, Chu Won Springer-Verlag 2009 Molecules and cells Vol.27 No.3

<P>Phytoestrogens are the natural compounds isolated from plants, which are structurally similar to animal estrogen, 17beta-estradiol. Tectoridin, a major isoflavone isolated from the rhizome of Belamcanda chinensis. Tectoridin is known as a phytoestrogen, however, the molecular mechanisms underlying its estrogenic effect are remained unclear. In this study we investigated the estrogenic signaling triggered by tectoridin as compared to a famous phytoestrogen, genistein in MCF-7 human breast cancer cells. Tectoridin scarcely binds to ER alpha as compared to 17beta-estradiol and genistein. Despite poor binding to ER alpha, tectoridin induced potent estrogenic effects, namely recovery of the population of cells in the S-phase after serum starvation, transactivation of the estrogen response element, and induction of MCF-7 cell proliferation. The tectoridin-induced estrogenic effect was severely abrogated by treatment with U0126, a specific MEK1/2 inhibitor. Tectoridin promoted phosphorylation of ERK1/2, but did not affect phosphorylation of ER alpha at Ser(118). It also increased cellular accumulation of cAMP, a hallmark of GPR30-mediated estrogen signaling. These data imply that tectoridin exerts its estrogenic effect mainly via the GPR30 and ERK-mediated rapid nongenomic estrogen signaling pathway. This property of tectoridin sets it aside from genistein where it exerts the estrogenic effects via both an ER-dependent genomic pathway and a GPR30-dependent nongenomic pathway.</P>

Tectoridin, a Poor Ligand of Estrogen Receptor alpha, Exerts Its Estrogenic Effects via an ERK-Dependent Pathway

Kyungsu Kang,Saet Byoul Lee,Sang Hoon Jung,Kwang Hyun Cha,Woo Dong Park,Young Chang Sohn,Chu Won Nho 한국분자세포생물학회 2009 Molecules and cells Vol.27 No.3

Phytoestrogens are the natural compounds isolated from plants, which are structurally similar to animal estrogen, 17β-estradiol. Tectoridin, a major isoflavone isolated from the rhizome of Belamcanda chinesis. Tectoridin is known as a phytoestrogen, however, the molecular mechanisms underlying its estrogenic effect are remained unclear. In this study we investigated the estrogenic signaling triggered by tectoridin as compared to a famous phytoestrogen, genistein in MCF-7 human breast cancer cells. Tectoridin scarcely binds to ER α as compared to 17β- estradiol and genistein. Despite poor binding to ER α, tectoridin induced potent estrogenic effects, namely recovery of the population of cells in the S-phase after serum starvation, transactivation of the estrogen response element, and induction of MCF-7 cell proliferation. The tectoridininduced estrogenic effect was severely abrogated by treatment with U0126, a specific MEK1/2 inhibitor. Tectoridin promoted phosphorylation of ERK1/2, but did not affect phosphorylation of ER α at Ser118. It also increased cellular accumulation of cAMP, a hallmark of GPR30- mediated estrogen signaling. These data imply that tectoridin exerts its estrogenic effect mainly via the GPR30 and ERK-mediated rapid nongenomic estrogen signaling pathway. This property of tectoridin sets it aside from genistein where it exerts the estrogenic effects via both an ERdependent genomic pathway and a GPR30-dependent nongenomic pathway.

Flow cytometric fluorescence pulse width analysis of etoposide-induced nuclear enlargement in HCT116 cells

Kang, Kyungsu,Lee, Saet Byoul,Yoo, Ji-Hye,Nho, Chu Won Springer Netherlands 2010 Biotechnology letters Vol.32 No.8

<P>Fluorescence pulse width can provide size information on the fluorescence-emitting particle, such as the nuclei of propidium iodide-stained cells. To analyze nuclear size in the present study, rather than perform the simple doublet discrimination approach usually employed in flow cytometric DNA content analyses, we assessed the pulse width of the propidium iodide fluorescence signal. The anti-cancer drug etoposide is reportedly cytostatic, can induce a strong G2/M arrest, and results in nuclear enlargement. Based on these characteristics, we used etoposide-treated HCT116 cells as our experimental model system. The fluorescence pulse widths (FL2-W) of etoposide-treated (10 μM, 48 h) cells were distributed at higher positions than those of vehicle control, so the peak FL2-W value of etoposide-treated cells appeared at 400 while those of vehicle control cells appeared at 200 and 270. These results were consistent with our microscopic observations. This etoposide-induced increase in FL2-W was more apparent in G2/M phase than other cell cycle phases, suggesting that etoposide-induced nuclear enlargement preferentially occurred in G2/M phase cells rather than in G0/G1 or S phase cells.</P><P><B>Electronic supplementary material</B></P><P>The online version of this article (doi:10.1007/s10529-010-0277-x) contains supplementary material, which is available to authorized users.</P>