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>

A Novel Topoisomerase Inhibitor, Daurinol, Suppresses Growth of HCT116 Cells with Low Hematological Toxicity Compared to Etoposide

Kang, Kyungsu,Oh, Seung Hyun,Yun, Ji Ho,Jho, Eun Hye,Kang, Ju-Hee,Batsuren, Dulamjav,Tunsag, Jigjidsuren,Park, Kwang Hwa,Kim, Minkyun,Nho, Chu Won Elsevier 2011 Neoplasia Vol.13 No.11

<P>We report that daurinol, a novel arylnaphthalene lignan, is a promising potential anticancer agent with adverse effects that are less severe than those of etoposide, a clinical anticancer agent. Despite its potent antitumor activity, clinical use of etoposide is limited because of its adverse effects, including myelosuppression and the development of secondary leukemia. Here, we comprehensively compared the mechanistic differences between daurinol and etoposide because they have similar chemical structures. Etoposide, a topoisomerase II poison, is known to attenuate cancer cell proliferation through the inhibition of DNA synthesis. Etoposide treatment induces G(2)/M arrest, severe DNA damage, and the formation of giant nuclei in HCT116 cells. We hypothesized that the induction of DNA damage and nuclear enlargement due to abnormal chromosomal conditions could give rise to genomic instability in both tumor cells and in actively dividing normal cells, resulting in the toxic adverse effects of etoposide. We found that daurinol is a catalytic inhibitor of human topoisomerase Il alpha, and it induces S-phase arrest through the enhanced expression of cyclins E and A and by activation of the ATM/Chk/Cdc25A pathway in HCT116 cells. However, daurinol treatment did not cause DNA damage or nuclear enlargement in vitro. Finally, we confirmed the in vivo antitumor effects and adverse effects of daurinol and etoposide in nude mice xenograft models. Daurinol displayed potent antitumor effects without any significant loss of body weight or changes in hematological parameters, whereas etoposide treatment led to decreased body weight and white blood cell, red blood cell, and hemoglobin concentration.</P>

Cell and Nuclear Enlargement of SW480 Cells Induced by a Plant Lignan, Arctigenin: Evaluation of Cellular DNA Content Using Fluorescence Microscopy and Flow Cytometry

Kang, Kyungsu,Lee, Hee Ju,Yoo, Ji-Hye,Jho, Eun Hye,Kim, Chul Young,Kim, Minkyun,Nho, Chu Won Mary Ann Liebert 2011 DNA and cell biology Vol.30 No.8

Secretome Profiling Reveals the Signaling Molecules of Apoptotic HCT116 Cells Induced by the Dietary Polyacetylene Gymnasterkoreayne B

Kang, Kyungsu,Song, Dae-Geun,Lee, Eun Ha,Lee, Kyung-Mi,Park, Young Gyun,Jung, Sang Hoon,Pan, Cheol-Ho,Nho, Chu Won American Chemical Society 2014 Journal of agricultural and food chemistry Vol.62 No.11

<P>Dietary polyacetylenes from various foods have been receiving attention as promising cancer chemopreventive agents. However, until now, the detailed molecular mechanism and the regulatory proteins underlying these effects have not been elucidated. We investigated the effects of gymnasterkoreayne B (GKB), a model dietary polyacetylene from wild vegetables, on the programmed cell death of HCT116 human colorectal cancer cells. GKB inhibited HCT116 cell proliferation by inducing apoptotic cell death. GKB treatment resulted in ROS accumulation, leading to the activation of both intrinsic and extrinsic apoptotic pathway. We also found that FN1, TGFB1, APP, SERPINE1, HSPD1, SOD1, TXN, and ACTN4 may act as secretory signaling molecules during GKB-induced apoptotic cell death using LC–MS/MS identification followed by spectrum counting, statistical calculation, and gene ontology analysis. The secretory proteins suggested in this study may be promising candidates involved in apoptotic cell death of cancer cells induced by GKB that warrant further functional study.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jafcau/2014/jafcau.2014.62.issue-11/jf404047z/production/images/medium/jf-2013-04047z_0006.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/jf404047z'>ACS Electronic Supporting Info</A></P>

Sulbutiamine Counteracts Trophic Factor Deprivation Induced Apoptotic Cell Death in Transformed Retinal Ganglion Cells

Kang, Kui Dong,Abdul Majid, Aman Shah,Kim, Kyung-A,Kang, Kyungsu,Ahn, Hong Ryul,Nho, Chu Won,Jung, Sang Hoon Springer-Verlag 2010 Neurochem Res Vol.35 No.11

Temperature-Aware Integrated DVFS and Power Gating for Executing Tasks With Runtime Distribution

Kyungsu Kang,Jungsoo Kim,Sungjoo Yoo,Chong-Min Kyung IEEE 2010 IEEE transactions on computer-aided design of inte Vol.29 No.9

<P>At high-operating temperature, chip cooling is crucial due to the exponential temperature dependence of leakage current. However, traditional cooling methods, e.g., power/clock gating applied when a temperature threshold is reached, often cause excessive performance degradation. In this paper, we propose a method for delivering lower energy consumption by integrating the cooling and running in a temperature-aware manner without incurring performance penalty. In order to further reduce the energy consumption, we exploited the runtime distribution of each sub-segment of a task called “bin” in an analytical manner such that time budget for cooling in each bin is allocated in proportion to the probability of the occurrence of the bin. We apply the proposed method to two realistic software programs, H.264 decoder and ray tracing and a benchmark program, equake. The experimental results show that the proposed method yields additional 19.4%-27.2% reduction in energy consumption compared with existing methods.</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>

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>

Runtime Power Management of 3-D Multi-Core Architectures Under Peak Power and Temperature Constraints

Kyungsu Kang,Jungsoo Kim,Sungjoo Yoo,Chong-Min Kyung IEEE 2011 IEEE transactions on computer-aided design of inte Vol.30 No.6

<P>3-D integration is a new technology that overcomes the limitations of 2-D integrated circuits, e.g., power and delay induced from long interconnect wires, by stacking multiple dies to increase logic integration density. However, chip-level power and peak temperature are the major performance limiters in 3-D multi-core architectures. In this paper, we propose a runtime power management method for both peak power and temperature-constrained 3-D multi-core systems in order to maximize the instruction throughput. The proposed method exploits dynamic temperature slack (defined as peak temperature constraint minus current temperature) and workload characteristics (e.g., instructions per cycle and memory-boundness) as well as thermal characteristics of 3-D stacking architectures. Compared with existing thermal-aware power management solutions for 3-D multi-core systems, our method yields up to 34.2% (average 18.5%) performance improvement in terms of instructions per second without significant additional energy consumption.</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.