• Title/Summary/Keyword: DU-145

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Suppression of MED19 expression by shRNA induces inhibition of cell proliferation and tumorigenesis in human prostate cancer cells

  • Cui, Xingang;Xu, Danfeng;Lv, Chao;Qu, Fajun;He, Jin;Chen, Ming;Liu, Yushan;Gao, Yi;Che, Jianping;Yao, Yacheng;Yu, Hongyu
    • BMB Reports
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    • v.44 no.8
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    • pp.547-552
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    • 2011
  • MED19 is a member of the Mediator that plays a key role in the activation and repression of signal transduction or the regulation of transcription in carcinomas. To tested the functional role of MED19 in human prostate cancer, we downregulated MED19 expression in prostate cancer cells (PC-3 and DU145) by lentivirus-mediated short hairpin (shRNA), and analyzed the effect of inhibition of MED19 on prostate cancer cell proliferation and tumorigenesis. The in vitro prostate cancer cell proliferation, colony formation, and in vivo tumor growth in nude mice xenografts was significantly reduced after the downregulation of MED19. Knockdown of MED19 caused S-phase arrest and induced apoptosis via modulation of Bid and Caspase 7. It was suggested that MED19 serves as a novel proliferation regulator that promotes growth of prostate cancer cells.

High glucose induces differentiation and adipogenesis in porcine muscle satellite cells via mTOR

  • Yue, Tao;Yin, Jingdong;Li, Fengna;Li, Defa;Du, Min
    • BMB Reports
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    • v.43 no.2
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    • pp.140-145
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    • 2010
  • The present study investigated whether the mammalian target of rapamycin (mTOR) signal pathway is involved in the regulation of high glucose-induced intramuscular adipogenesis in porcine muscle satellite cells. High glucose (25 mM) dramatically increased intracellular lipid accumulation in cells during the 10-day adipogenic differentiation period. The expressions of CCAAT/enhancer binding protein-$\alpha$ (C/EBP-$\alpha$) and fatty acid synthase (FAS) protein were gradually enhanced during the 10-day duration while mTOR phosphorylation and sterol-regulatory- element-binding protein (SREBP)-1c protein were induced on day 4. Moreover, inhibition of mTOR activity by rapamycin resulted in a reduction of SREBP-1c protein expression and adipogenesis in cells. Collectively, our findings suggest that the adipogenic differentiation of porcine muscle satellite cells and a succeeding extensive adipogenesis, which is triggered by high glucose, is initiated by the mTOR signal pathway through the activation of SREBP-1c protein. This process is previously uncharacterized and suggests a cellular mechanism may be involved in ectopic lipid deposition in skeletal muscle during type 2 diabetes.

Synthesis and Biological Evaluation of Novel GSK-3β Inhibitors as Anticancer Agents

  • Choi, Min-Jeong;Oh, Da-Won;Jang, Jae-Wan;Cho, Yong-Seo;Seo, Seon-Hee;Jeong, Kyu-Sung;Ko, Soo-Young;Pae, Ae-Nim
    • Bulletin of the Korean Chemical Society
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    • v.32 no.6
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    • pp.2015-2020
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    • 2011
  • A series of isoxazol-indolin-2-one was designed for GSK-3${\beta}$ inhibitors as novel anticancer agents based on their binding mode analysis in GSK-3${\beta}$ crystal structure. Total 21 compounds were synthesized and evaluated for their inhibitory activity against two tumor cell lines (DU145 and HT29). Most of the synthesized compounds were potent with above 80% inhibitory activity at 100 ${\mu}M$, and several compounds were examined for inhibitory activity against GSK-3${\beta}$. Among them, 15(Z) ($R_1$=H, $R_2$=3-Cl-phenyl) was most active with 78% inhibition of tumor cell line (HT29) at 20 ${\mu}M$ and 72% inhibition of GSK-3${\beta}$ at 20 ${\mu}M$.

Chestnut extract induces apoptosis in AGS human gastric cancer cells

  • Lee, Hyun-Sook;Kim, Eun-Ji;Kim, Sun-Hyo
    • Nutrition Research and Practice
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    • v.5 no.3
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    • pp.185-191
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    • 2011
  • In Korea, chestnut production is increasing each year, but consumption is far below production. We investigated the effect of chestnut extracts on antioxidant activity and anticancer effects. Ethanol extracts of raw chestnut (RCE) or chestnut powder (CPE) had dose-dependent superoxide scavenging activity. Viable numbers of MDA-MD-231 human breast cancer cells, DU145 human prostate cancer cells, and AGS human gastric cancer cells decreased by 18, 31, and 69%, respectively, following treatment with $200{\mu}g/mL$ CPE for 24 hr. CPE at various concentrations ($0-200{\mu}g/mL$) markedly decreased AGS cell viability and increased apoptotic cell death dose and time dependently. CPE increased the levels of cleaved caspase-8, -7, -3, and poly (ADP-ribose) polymerase in a dose-dependent manner but not cleaved caspase-9. CPR exerted no effects on Bcl-2 and Bax levels. The level of X-linked inhibitor of apoptosis protein decreased within a narrow range following CPE treatment. The levels of Trail, DR4, and Fas-L increased dose-dependently in CPE-treated AGS cells. These results show that CPE decreases growth and induces apoptosis in AGS gastric cancer cells and that activation of the death receptor pathway contributes to CPE-induced apoptosis in AGS cells. In conclusion, CPE had more of an effect on gastric cancer cells than breast or prostate cancer cells, suggesting that chestnuts would have a positive effect against gastric cancer.

Cytotoxicity of Shikonin Metabolites with Biotransformation of Human Intestinal Bacteria

  • Min, Byung-Sun;Meselhy, Meselhy-R.;Hattori, Masao;Kim, Hwan-Mook;Kim, Young-Ho
    • Journal of Microbiology and Biotechnology
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    • v.10 no.4
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    • pp.514-517
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    • 2000
  • Abstracts Six shikonin metabolites were obtained from human intestinal bacteria, Bacteriodes fragilis subsp. thetaotus. following biotransformation. The transformation of shikonin (1) was performed anaerobically for 3 day at $37^{\circ}C$ in thc bacterial suspension of B. Fagilis which was cultured overnight in GAM broth. The incubation mixture \vas extracted with EtGAc Lo give a dark-brown residue. The residue was apphed to a silica gel column, which was eluted successively with hexane (Fr. A), $CHCl_3$ (Fr. B), and $CHCl_3$:MeOH (9:I) (Fr. C). Six metabolites. Fr.A (2 and 3), Fr. B (6 and 7), and Fr. C (4 and 5) were isolated by repeated silica gel column chromatography, preparatlVe TLC, followed by Sephadex LH-20. In vitro cytotoxicities were tested against human tumor cell lines; PC-3 (prostate), ACHN (renal), A549 (lung), SW620 (colon), KS62 (leukemia), and Du145 (prostate). The shikonin metabolites 2. 4, 5, and 6 showed weaker cytotoxicity than the parenL shikonin (1). whereas shikonin monomenc metabolite 3 ($ED_{50}{\;}O.44-{\;}1.22{\;}\mu\textrm{g}/ml$) and dimeric metabolite 7 ($ED_{50}{\;}O.48-{\;}2.35{\;}\mu\textrm{g}/ml$) exhibited stronger activities compared with adriamycin, which was used as the positive control.ontrol.

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Combined Treatment with Stattic and Docetaxel Alters the Bax/Bcl-2 Gene Expression Ratio in Human Prostate Cancer Cells

  • Mohammadian, Jamal;Sabzichi, Mehdi;Molavi, Ommoleila;Shanehbandi, Dariush;Samadi, Nasser
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.11
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    • pp.5031-5035
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    • 2016
  • Docetaxel, recognized as a stabilizing microtubule agent, is frequently administrated as a first line treatment for prostate cancers. Due to high side effects of monotherapy, however, combinations with novel adjuvants have emerged as an alternative strategy in cancer therapy protocols. Here, we investigated the combined effects of stattic and docetaxel on the DU145 prostate cancer cell line. Cytotoxicity was evaluated by MTT assay. To understand molecular mechanisms of stattic action, apoptotic related genes including Bcl-2, Mcl-1, Survivin and Bax were evaluated by real-time RT-PCR. Alteration in the expression of pro-apoptotic Bax and anti-apoptotic Bcl-2 genes and Bax/Bcl-2 ratio were investigated via the $2^{{\Delta}{\Delta}CT}$ method. The $IC_{50}$ values for docetaxel and stattic were $3.7{\pm}0.9nM$ and $4.6{\pm}0.8{\mu}M$, respectively. Evaluation of key gene expression levels revealed a noticeable decrease in antiapoptotic Bcl-2 and Mcl-1 along with an increase in pro-apoptotic Bax mRNA levels (p<0.05). Our results suggest that combination of a STAT3 inhibitor with doctaxel can be considered as a potent strategy for induction of apoptosis via increasing Bax mRNA expression.

A Study on "Hyang Yak Gu Geup Bang" (향약구급방(鄕藥救急方)에 대한 연구)

  • Nyeong, Ok-Chung;Kim, Joo-Tae;Lee, Hyun-Jeong;Kim, Sang-Un;Lee, Si-Hyeong;Keum, Kyung-Soo
    • Journal of the Korean Institute of Oriental Medical Informatics
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    • v.17 no.1
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    • pp.69-145
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    • 2011
  • Characteristics Regarding Xiang Yao (Hyang Yag) Jiu Ji Fang Life Saving Local Botanical prescriptions in Medical Research Xiang Yao Jiu Ji Fang is Korea's most ancient extant medical manuscript. It was first published between 1232 and 1251 during the Goguryeo period (Gao Zong) by the (Jianghuadao Da Cang Du Jian) Great Storage Depository Under Capital Supervision. The entire work is divided into three scrolls named the front, middle and back parts. There is also an appendix titled Fangzhong Xiang Yao Mu Cao Bu 'Catalogue of Medicines in the Local Botanicals prescriptions' in one volume. The contents comprise discussion of internal medicine diseases, external medicine diseases, commentaries on sexually transmitted diseases, diseases caused by parasites and bugs, diseases of the five orifices, gynecological diseases and pediatric diseases, in all totaling fifty three types of disease. The prescriptions record 180 types of xiangyao or hyang yag-local botanicals representing the beginning of an independent Korean path of development. Owing to the development during the Goguryeo period of medical material left to us by history, investigation and research in the area of hyang yag local botanicals has bequeathed us methods used in the contemporary period. Through the related comprehensive annotated explanatory notes and documents, much analysis and discussion is taking shape.

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Effects of NH4F and H2O on the Geometry of TiO2 Nanotubes (TiO2 나노튜브 형상에 미치는 NH4F와 H2O의 영향)

  • Gim, Geon-Du;Jang, Sang-Soon;Kim, Heesan
    • Corrosion Science and Technology
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    • v.17 no.3
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    • pp.138-145
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    • 2018
  • The aim of this work is the attainment of the $TiO_2-nanotube$ photocatalytic-growth condition using anodization, whereby the $NH_4F-H_2O$ weight ratio is appropriately controlled. We fabricated the $TiO_2$ nanotubes using a two-step anodization (first step is 1 hr; second step is 30 hr) under the ambient pressure and the room temperature at 60 V in ethylene-glycol solutions to investigate the effects of the $NH_4F$(0.1,0.3,0.5wt%) and $H_2O$(1-3wt%) on the $TiO_2-nanotube$ geometry and the photocatalytic efficiency. Further, the decomposition efficiency of the methylene blue on the $TiO_2$ nanotubes by the UN radiation depended on the geometrical change of the nanotube geometry, indicating the proportionality of the decomposition efficiency to the surface area that was affected by the $NH_4F$ and $H_2O$ concentrations. As the $NH_4F$ weight was increased, the surface area initially decreased but slightly increased later, and the length consistently increased. As the $H_2O$ weight was increased, the surface area and length initially increased, but later decreased with the 3 wt% $H_2O$.

Synergistic effect of curcumin on epigallocatechin gallate-induced anticancer action in PC3 prostate cancer cells

  • Eom, Dae-Woon;Lee, Ji Hwan;Kim, Young-Joo;Hwang, Gwi Seo;Kim, Su-Nam;Kwak, Jin Ho;Cheon, Gab Jin;Kim, Ki Hyun;Jang, Hyuk-Jai;Ham, Jungyeob;Kang, Ki Sung;Yamabe, Noriko
    • BMB Reports
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    • v.48 no.8
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    • pp.461-466
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    • 2015
  • Epigallocatechin gallate (EGCG) and curcumin are well known to naturally-occurring anticancer agents. The aim of this study was to verify the combined beneficial anticancer effects of curcumin and EGCG on PC3 prostate cancer cells, which are resistant to chemotherapy drugs and apoptosis inducers. EGCG showed weaker inhibitory effect on PC3 cell proliferation than two other prostate cancer cell lines, LNCaP and DU145. Co-treatment of curcumin improved antiproliferative effect of EGCG on PC3 cells. The protein expressions of p21 were significantly increased by the co-treatment of EGCG and curcumin, whereas it was not changed by the treatment with each individual compound. Moreover, treatments of EGCG and curcumin arrested both S and G2/M phases of PC3 cells. These results suggest that the enhanced inhibitory effect of EGCG on PC3 cell proliferation by curcumin was mediated by the synergic up-regulation of p21-induced growth arrest and followed cell growth arrest. [BMB Reports 2015; 48(8): 461-466]

Effects of Aralia continentalis Root Extract on Cell Proliferation and Apoptosis in Human Promyelocytic Leukemia HL-60 Cells

  • Lim Hae-Young;Oh Ha-Lim;Lee Chul-Hoon
    • Journal of Microbiology and Biotechnology
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    • v.16 no.9
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    • pp.1399-1404
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    • 2006
  • The roots of Aralia continentalis (AC) have been used traditionally in Korean as a folk medicine for anti-inflammation and as an anti-rheumatic. In this study, we report that the ethyl acetate-soluble traction (ACE) of the methanolic extract of AC root inhibited the cell growth of various human cancer cell lines and induced apoptosis of HL-60, human promyelocytic leukemia cells. Its $IC_{50}$ values on growth inhibition were estimated to be $56.3{\mu}g/ml$ on HL-60, $87.2{\mu}g/ml$ on HepG2, $93.2{\mu}g/ml$ on HeLa, $135.5{\mu}g/ml$ on DU-145, and $135.8{\mu}g/ml$ on HT-29 cells. Interestingly, ACE showed no antiproliferative effect on normal lymphocyte cells used as control. Furthermore, nuclear DAPI staining revealed the typical nuclear features of apoptosis in the HL-60 cells exposed to $80{\mu}g/ml$ ACE, and a flow cytometric analysis of the HL-60 cells using propidium iodide showed that the apoptotic cell population increased gradually from 5% at 0 h to 16% at 12 h and 20% at 24 h after treated with $50{\mu}g/ml$ of ACE. TUNEL assay also revealed the apoptotic induction of the HL-60 cells treated with ACE. To obtain further information on the ACE-induced apoptosis, the expression level of certain apoptosis-associated proteins was examined using a Western blot analysis. Treatment of the HL-60 cells with ACE resulted in the activation of caspase-3, and subsequent proteolytic cleavage of poly(ADP-ribose) polymerase (PARP). The above results confirmed that the apoptosis in the HL-60 cells was induced by ACE, and that caspase-3-mediated PARP cleavage was involved in the process.