• Title/Summary/Keyword: Ligand Effects

Search Result 404, Processing Time 0.024 seconds

Green Tea (-) Epigallocatechin-gallate Induces the Apoptotic Death of Prostate Cancer Cells (녹차 (-)Epigallocatechin-gallate에 의한 전립선암 세포주 DU145 세포고사 기전)

  • 이지현;정원훈;박지선;신미경;손희숙;박래길
    • Toxicological Research
    • /
    • v.18 no.2
    • /
    • pp.183-190
    • /
    • 2002
  • The mechanism by which catechin-mediated cytotoxicity against tumor cells remains to be elusive. To elucidate the mechanical mights of anti-tumor effects, (-)epigallocatechin-gallate (EGCG) of catechin was applied to human prostate cancer DU 145 cells. Cell viability was measured by crystal violet staining. Cell lysates were wed to measure the catalytic activity of caspases by using fluorogenic peptide: Ac-DEVD-AMC for caspase-3 protease, Z-IETD-AFC for caspase-8 protease, Ac-LEHD-AFC for caspase-9 protease as substrates. The equal amounts of protein from cell lysate was separated on SDS-PAGE and analyzed by western blotting with anti-Fas antibody, anti-FasL antibody, anti-BCL2 antibody and anti-Bax antibody. (-)EGCG induced the death of DUl45 cells, which was revealed as apoptosis shown by DNA fragmentation. (-)EGCG induced the activation of caspase family cysteine proteases including caspase-3, -8 and -9 proteases in DU145 cells. Also, (-)EGCG increased the expression of Fas and Fas ligand (FasL) protein in DU145 colls. The expression level of BCL2 was decreased in (-)EGCG treated DU145 cells, whereas Bax protein was increased in a time-dependent manner. We suggest that (-)EGCG-induced apoptosis of DU145 cells is mediated by signaling pathway involving caspase family cysteine protease, mitochondrial BCL2-family protein and Fas/FasL.

Studies on the Synthesis and Structure of Macrocyclic Complexes for Transition Metals. (Part 1) Effects of Stability Constant on the Co-formation of Mixed Chelates (EDTA and IMDA) with Lanthanon (La, Nd, Gd, Ho, Yb) (전이금속 착물들의 합성 및 결정구조 연구 (제 1 보) EDTA 와 IMDA 복합 킬레이트가 란탄족 원소들 (La, Nd, Gd, Ho, Yb)의 안정도 상수에 미치는 영향)

  • Young-Gu Ha;E. Y. Kim;Q. Won Choi;Hasuck Kim
    • Journal of the Korean Chemical Society
    • /
    • v.31 no.5
    • /
    • pp.434-443
    • /
    • 1987
  • The formation constants of the complexes between Ln-EDTA 1 : 1 complex and IMDA have been investigated by a potentiometric titration method at 20.0${\pm}$0.2 degree C and ${\mu}$ = 0.1 (KNO$_3$). Unusually large stability in Ln(EDTA) mixed ligand complexes was found. Trends in the formation constants vs. atomic number of the lanthanide metals were discussed on the basis of coordination number and ionic radius of the metals.

  • PDF

The Complex Formation of p-Aminoazobenzene and its Derivatives with Fe(Ⅲ) and Mn(Ⅱ) in Organic Solvents (유기용매중에서 Fe(Ⅲ), Mn(Ⅱ)과 p-aminoazobenzene 및 그 유도체와의 착물형성에 관한 연구)

  • Eun Soo Kim
    • Journal of the Korean Chemical Society
    • /
    • v.32 no.5
    • /
    • pp.464-475
    • /
    • 1988
  • The complex formation of p-aminoazobenzene and its derivatives with Fe(III) and Mn(II) has been studied by UV and IR spectroscopy and conductometry. The effects of solvents, donor basicity, and other factors on the formation of these complexes have been examined. The vatio of metal to ligand for the complexes formed is 1 : 1, both in the solid state and in solution. The stability constants of Fe(III)-donor and Mn(II)-donor complexes are in the range of 10$^2$∼10$^4$ and 0.1∼1, respectively. The absorptivities are ~10$^4$ and ∼10$^3$ l/mol${\cdot}$cm respectively. Thermodynamic properties such as ${\Delta}H^{\circ}$, ${\Delta}G^{\circ}$ and ${\Delta}S^{\circ}$ are calculated from their stability constants utilizing Van't Hoff equation.

  • PDF

Afatinib ameliorates osteoclast differentiation and function through downregulation of RANK signaling pathways

  • Ihn, Hye Jung;Kim, Ju Ang;Bae, Yong Chul;Shin, Hong-In;Baek, Moon-Chang;Park, Eui Kyun
    • BMB Reports
    • /
    • v.50 no.3
    • /
    • pp.150-155
    • /
    • 2017
  • Non-small-cell lung cancer (NSCLC) is the third most common cancer that spreads to the bone, resulting in osteolytic lesions caused by hyperactivation of osteoclasts. Activating mutations in epidermal growth factor receptor-tyrosine kinase (EGF-TK) are frequently associated with NSCLC, and afatinib is a first-line therapeutic drug, irreversibly targeting EGF-TK. However, the effects of afatinib on osteoclast differentiation and activation as well as the underlying mechanism remain unclear. In this study, afatinib significantly suppressed receptor activator of nuclear factor ${\kappa}B$ (RANK) ligand (RANKL)-induced osteoclast formation in bone marrow macrophages (BMMs). Consistently, afatinib inhibited the expression of osteoclast marker genes, whereas, it upregulated the expression of negative modulator genes. The bone resorbing activity of osteoclasts was also abrogated by afatinib. In addition, afatinib significantly inhibited RANKL-mediated Akt/protein kinase B and c-Jun N-terminal kinase phosphorylation. These results suggest that afatinib substantially suppresses osteoclastogenesis by downregulating RANK signaling pathways, and thus may reduce osteolysis after bone metastasis.

Decontaminatin Techniques using Liquid/Supercritical $CO_2$ (액체 및 초임계 이산화탄소를 이용한 제염법)

  • 박광헌;김홍두;김학원;고문성;윤청현
    • Proceedings of the Korean Radioactive Waste Society Conference
    • /
    • 2003.11a
    • /
    • pp.650-654
    • /
    • 2003
  • A major problem of nuclear energy is the production of radioactive wastes. Needs for more environmentally favorable method to decontaminate radioactive contaminants make the use of liqui $d^ercritical $CO_2$ as a solvent medium. In removing radioactive metallic contaminants under $CO_2$ solvent, two methods - use of chelating ligands and that of water in $CO_2$ emulsion-are possible. In the chelating ligand method, a combination of ligands that can make synergistic effects seems important. We discuss about the properties of microemulsion formed by F-AOT and that by non-ionic surfactant. By adding acid in water core, decontamination of metallic parts, soils were possible. The rate of metal surface dissolution to the microemulsion solution was measured by QCM. The possibility of recovering the surfactants after use is also mentioned.ed.

  • PDF

Biotin-Conjugated Block Copolymeric Nanoparticles as Tumor-Targeted Drug Delivery Systems

  • Kim, So-Yeon;Cho, Seung-Hea;Lee, Young-Moo
    • Macromolecular Research
    • /
    • v.15 no.7
    • /
    • pp.646-655
    • /
    • 2007
  • To achieve targeted drug delivery for chemotherapy, a ligand-mediated nanoparticulate drug carrier was designed, which could identity a specific receptor on the surfaces of tumor cells. Biodegradable poly(ethylene oxide)/poly$({\varepsilon}-caprolactone)$ (PEG/PCL) amphiphilic block copolymers coupled to biotin ligands were synthesized with a variety of PEG/PCL compositions. Block copolymeric nanoparticles harboring the anticancer drug paclitaxel were prepared via micelle formation in aqueous solution. The size of the biotin-conjugated PEG/PCL nanoparticles was determined by light scattering measurements to be 88-118 nm, depending on the molecular weight of the block copolymer, and remained less than 120 nm even after paclitaxel loading. From an in vitro release study, biotin-conjugated PEG/PCL nanoparticles containing paclitaxel evidenced sustained release profiles of the drug with no initial burst effect. The biotin-conjugated PEG/PCL block copolymer itself evidenced no significant adverse effects on cell viability at $0.005-1.0{\mu}g/mL$ of nanoparticle suspension regardless of cell type (normal human fibroblasts and HeLa cells). However, biotin-conjugated PEG/PCL harboring paclitaxel evidenced a much higher cytotoxicity for cancer cells than was observed in the PEG/PCL nanoparticles without the biotin group. These results showed that the biotin-conjugated nanoparticles could improve the selective delivery of paclitaxel into cancer cells via interactions with over-expressed biotin receptors on the surfaces of cancer cells.

Cathodic Stripping Voltammetric Study of Tin(Ⅱ)-Cupferron Complex (Tin(Ⅱ)-Cupferron 착물에 대한 음극벗김전압전류법적 연구)

  • Sohn, Se Chul;Seo, Moo Yul;Jee, kwang Yong;Choi, In kyu
    • Journal of the Korean Chemical Society
    • /
    • v.39 no.1
    • /
    • pp.23-28
    • /
    • 1995
  • Differential-pulse cathodic stripping voltammetry was applied to the Sn(II)-cupferron complex in 0.1 M acetate buffer solution (pH 4.20). Effects of solution pH, ligand concentration, accumulation potential, and accumulation time on the reduction peak current for the adsorptive complex of Sn(II)-cupferron were investigated. Interferences by other metal cations that affected on reduction peak current were also discussed. The detection limit was 3.1${\times}$10-9 M (0.37 ppb) of Sn(II) with 60 seconds accumulation time. The relative standard deviation (n=8) for 5${\times}$10-8 M Sn(II) was 3.0%.

  • PDF

Administration of Agonistic Anti-4-1BB Monoclonal Antibody Inhibits Melanoma Metastasis Via IFN-${\gamma}$ Production

  • Ju, Seong-A;Lee, Sang-Chul;Seok, Moon-Hong;Kim, Byung-Sam
    • Animal cells and systems
    • /
    • v.8 no.2
    • /
    • pp.117-123
    • /
    • 2004
  • The purpose of this study was to analyze inhibitory effects of anti-4-1BB monoclonal antibody on melanoma metastasis The 4-1BB (CD137) T cell molecule is a member of the TNF receptor family and its activation by either 4-1BB ligand or antibody induces T cell activation and growth. In the present study, administration of anti-4-1BB mAb induced inhibition of melanoma metastasis. Agonistic anti-4-1BB mAb induced not only CD$8^+$4-1BBT cells but also CD$8^+$IFN-${\gamma}$$^{+}$ T cell population. In the presence of anti-CD3 antibody, lymphocytes produced high levels of IFN-${\gamma}$ and low levels of IL-4 in anti-4-1BB mAb treated group. Exposure of melanoma cells to IFN-${\gamma}$ induced expression of MHC-I molecules. Thus, the increase in number of CD$8^+$T cells and enhanced MHC-I expression on B16F10 cells by augmented IFN-${\gamma}$ production in response to anti-4-1BB mAb may result in suppression of tumor growth and metastasis.s.

Effect of Sochungryong-tang Extract on Osteoclast Differentiation and Bone-pit Formation (소청룡탕이 파골세포 분화억제와 골흡수에 미치는 영향)

  • Ahn, Min-Youn;Lim, Hyung-Ho
    • The Journal of Korean Medicine
    • /
    • v.38 no.3
    • /
    • pp.59-72
    • /
    • 2017
  • Objectives: This study was performed to evaluate effects of Sochungryong-tang Extract(SRE) on osteoclast differentiation and bone resorptionin order to find out the possibility for clinical use in preventing and treating osteoporosis. Methods: To evaluate the effect of SRE on osteoclast differentiation, we induced RAW 264. 7 cells to be differentiated to osteoclasts by RANKL (receptor activator of nuclear $factor-{\kappa}B$ ligand). We measured effect on TRAP (Tartrate-resistant acid phosphatase), NFATc, cathepsin K, MMP-9, inflammation related factors, histogenesis factors and bone resorption. Results: SRE decreased osteoclast differentiation, and also decreased expression of bone resorbing factors such as MMP-9, cathepsin K, TRAP, NFATc1, MITF, c-Fos, osteoclast stimulatory transmembrane protein, calcitonin receptor in RANKL-induced osteoclast. SRE also decreased Cyclooxygenase-2, indusible nitric oxide synthase, $TNF-{\alpha}$, which are thought to be related with the inflammatory bone destruction. Conclusion: SRE inhibits osteoclast differentiation and bone resorption. The results indicate that the BHT extract can potentially be applied for preventing and treating osteoporosis.

Inhibitory Effect of Snake Venom Toxin on Colorectal Cancer HCT116 Cells Growth through Induction of Intrinsic or Extrinsic Apoptosis

  • Kim, Kyung Tae;Song, Ho Sueb
    • Journal of Acupuncture Research
    • /
    • v.30 no.1
    • /
    • pp.43-55
    • /
    • 2013
  • I investigated whether snake venom toxin(SVT) from Vipera lebetina turanica enhances the apoptosis ability of tumor necrosis factor(TNF)-related apoptosis-inducing ligand(TRAIL) in cancer cells. TRAIL inhibited HCT116 cell growth in a dose-dependent manner. Consistent with cell growth inhibition, the expression of TRAIL receptors; DR4 and DR5 was significantly increased as well as apoptosis related proteins such as cleaved caspase-3, 8, 9 and Bax. However, the expression of survival proteins(eg, cFLIP, survivin, XIAP and Bcl2) was suppressed by the combination treatment of SVT and TRAIL. Pretreatment with the reactive oxygen species(ROS) scavenger N-acetylcysteine reduced the SVT and TRAIL-induced upregulation of DR4 and DR5 expression and expression of the apoptosis related protein such as caspase-3 and-9 as well as cell growth inhibitory effects. The collective results suggest that SVT facilitates TRAIL-induced apoptosis in human colorectal cancer HCT116 cells through up-regulation of the TRAIL receptors; DR4 and DR5 via ROS pathway signals.