• Title/Summary/Keyword: BET inhibitor

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Transcriptome analysis of iBET-151, a BET inhibitor alone and in combination with paclitaxel in gastric cancer cells

  • Kang, Sun Kyoung;Bae, Hyun Joo;Kwon, Woo Sun;Che, Jingmin;Kim, Tae Soo;Chung, Hyun Cheol;Rha, Sun Young
    • Genomics & Informatics
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    • v.18 no.4
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    • pp.37.1-37.11
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    • 2020
  • BET inhibitor, as an epigenetic regulator inhibitor, reduces the expression of oncogenes such as Myc and Bcl-2, which affects cancer growth and development. However, it has modest activity because of the narrow therapeutic index. Therefore, combination therapy is necessary to increase the anti-tumor effect. Paclitaxel, an anti-mitotic inhibitor, is used as second-line therapy for gastric cancer (GC) as a monotherapy or combination. In this study, we performed RNA sequencing of GC cells treated with iBET-151 and/or paclitaxel to identify the differentially expressed genes associated with possible mechanisms of synergistic effect. We also performed Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses to determine the most enriched terms and pathways of upregulated and downregulated genes. We found 460 genes in which iBET-151 and paclitaxel combination treatment changed more than single-treatment or no-treatment. Thus, additional functional studies are needed, but our results provide the first evidence of the synergistic effect between iBET-151 and paclitaxel in regulating the transcriptome of GC cells.

Isolation and Structure Determination of a Cholesterol Esterase Inhibitor from Ganoderma lucidum

  • Kim, Shin-Duk
    • Journal of Microbiology and Biotechnology
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    • v.20 no.11
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    • pp.1521-1523
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    • 2010
  • Bioassay-guided fractionation of a methanol extract of Ganoderma lucidum gave a pure cholesterol esterase inhibitor. On the basis of spectroscopic analysis and comparison with data from the literature, the structure of this compound was identified as $5{\alpha},8{\alpha}$-epidioxyergosta-6,22-dien-$3{\bet}$-ol (compound I). This compound inhibited cholesterol esterase activity with an $IC_{50}$ value of $42{\mu}M$. Lineweaver-Burk plot analysis revealed that compound I is a noncompetitive inhibitor. The findings of this study suggest that compound I may be the active principle of the hypocholesterolemic effect of Ganoderma lucidum.

JQ1, a BET inhibitor, controls TLR4-induced IL-10 production in regulatory B cells by BRD4-NF-κB axis

  • Lee, Min Bum;Lee, Jun-Ho;Hong, Seong Hwi;You, Jueng Soo;Nam, Seung Taek;Kim, Hyun Woo;Park, Young Hwan;Lee, Dajeong;Min, Keun Young;Park, Yeong-Min;Kim, Young Mi;Kim, Hyuk Soon;Choi, Wahn Soo
    • BMB Reports
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    • v.50 no.12
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    • pp.640-646
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    • 2017
  • Regulatory B cells, also well-known as IL-10-producing B cells, play a role in the suppression of inflammatory responses. However, the epigenetic modulation of regulatory B cells is largely unknown. Recent studies showed that the bromodomain and extra-terminal domain (BET) protein inhibitor JQ1 controls the expression of various genes involving cell proliferation and cell cycle. However, the role of BET proteins on development of regulatory B cells is not reported. In this study, JQ1 potently suppressed IL-10 expression and secretion in murine splenic and peritoneal B cells. While bromodomain-containing protein 4 (BRD4) was associated with $NF-{\kappa}B$ on IL-10 promoter region by LPS stimulation, JQ1 interfered the interaction of BRD4 with $NF-{\kappa}B$ on IL-10 promoter. In summary, BRD4 is essential for toll like receptor 4 (TLR4)-mediated IL-10 expression, suggesting JQ1 could be a potential candidate in regulating IL-10-producing regulatory B cells in cancer.

Methane gas sensing effect of SnO$_{2}$ fine particle mixed with inhibitor to crystal growth (결정성장 억제재를 첨가한 SnO$_{2}$ 미세입자의 메탄가스 감지효과)

  • 홍영호;강봉휘;이덕동
    • Electrical & Electronic Materials
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    • v.9 no.1
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    • pp.38-43
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    • 1996
  • A coprecipitation method was used for preparing Ca and Pt doped $SnO_2$ fine powder. Components of the powder were investigated by XPS and SIMS. Crystallite size and specific surface area were investigated by TEM, XRD, and BET analysis. $SnO_2$(Ca)/Pt based thick film devices were prepared by a screen printing technique for methane gas detection. Then sensing characteristics of the devices were investigated. As Ca and Pt added, the crystal growth of $SnO_2$ was suppressed during calcining and sintering, and the sensitivity of $SnO_2$(Ca)/Pt thick film to methane gas was enhanced. For the Pt doped $SnO_2$ fine particle, the thick film device shows sensitivity of about 83% to 2000 ppm methane gas at an operating temperature of >$400^{\circ}C$.

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Mechanism of Biological Nitrogen Fixation in Azotobacter vinelandii (Azotobacter vinelandii에서의 생물학적 질소고정 작용 메카니즘)

  • Kim, Yong-Ung;Han, Jae-Hong
    • Applied Biological Chemistry
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    • v.48 no.3
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    • pp.189-200
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    • 2005
  • Biological nitrogen fixation is an important process for academic and industrial aspects. This review will briefly compare industrial and biological nitrogen fixation and cover the characteristics of biological nitrogen fixation studied in Azotobacter vinelandii. Various organisms can carry out biological nitrogen fixation and recently the researches on the reaction mechanism were concentrated on the free-living microorganism, A. vinelandii. Nitrogen fixation, which transforms atmospheric $N_2$ into ammonia, is chemically a reduction reaction requiring electron donation. Nitrogenase, the biological nitrgen fixer, accepts electrons from biological electron donors, and transfers them to the active site, FeMo-cofactor, through $Fe_4S_4$ cluster in Fe protein and P-cluster in MoFe protein. The electron transport and the proton transport are very important processes in the nitrogenase catalysis to understand its reaction mechanism, and the interactions between FeMo-cofactor and nitrogen molecule are at the center of biological nitrogen fixation mechanism. Spectroscopic studies including protein X-ray crystallography, EPR and $M{\ddot{o}}ssbauer$, biochemical approaches including substrate and inhibitor interactions as well as site-directed mutation study, and chemical approach to synthesize the FeMo-cofactor model compounds were used for biological nitrogen fixation study. Recent research results from these area were presented, and finally, a new nitrogenase reaction mechanism will be proposed based on the various research results.