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Sample records for actinium 231

  1. Spectroscopic and computational investigation of actinium coordination chemistry

    Science.gov (United States)

    Ferrier, Maryline G.; Batista, Enrique R.; Berg, John M.; Birnbaum, Eva R.; Cross, Justin N.; Engle, Jonathan W.; La Pierre, Henry S.; Kozimor, Stosh A.; Lezama Pacheco, Juan S.; Stein, Benjamin W.; Stieber, S. Chantal E.; Wilson, Justin J.

    2016-08-01

    Actinium-225 is a promising isotope for targeted-α therapy. Unfortunately, progress in developing chelators for medicinal applications has been hindered by a limited understanding of actinium chemistry. This knowledge gap is primarily associated with handling actinium, as it is highly radioactive and in short supply. Hence, AcIII reactivity is often inferred from the lanthanides and minor actinides (that is, Am, Cm), with limited success. Here we overcome these challenges and characterize actinium in HCl solutions using X-ray absorption spectroscopy and molecular dynamics density functional theory. The Ac-Cl and Ac-OH2O distances are measured to be 2.95(3) and 2.59(3) Å, respectively. The X-ray absorption spectroscopy comparisons between AcIII and AmIII in HCl solutions indicate AcIII coordinates more inner-sphere Cl1- ligands (3.2+/-1.1) than AmIII (0.8+/-0.3). These results imply diverse reactivity for the +3 actinides and highlight the unexpected and unique AcIII chemical behaviour.

  2. Spectroscopic and computational investigation of actinium coordination chemistry

    Science.gov (United States)

    Ferrier, Maryline G.; Batista, Enrique R.; Berg, John M.; Birnbaum, Eva R.; Cross, Justin N.; Engle, Jonathan W.; La Pierre, Henry S.; Kozimor, Stosh A.; Lezama Pacheco, Juan S.; Stein, Benjamin W.; Stieber, S. Chantal E.; Wilson, Justin J.

    2016-01-01

    Actinium-225 is a promising isotope for targeted-α therapy. Unfortunately, progress in developing chelators for medicinal applications has been hindered by a limited understanding of actinium chemistry. This knowledge gap is primarily associated with handling actinium, as it is highly radioactive and in short supply. Hence, AcIII reactivity is often inferred from the lanthanides and minor actinides (that is, Am, Cm), with limited success. Here we overcome these challenges and characterize actinium in HCl solutions using X-ray absorption spectroscopy and molecular dynamics density functional theory. The Ac–Cl and Ac–OH2O distances are measured to be 2.95(3) and 2.59(3) Å, respectively. The X-ray absorption spectroscopy comparisons between AcIII and AmIII in HCl solutions indicate AcIII coordinates more inner-sphere Cl1– ligands (3.2±1.1) than AmIII (0.8±0.3). These results imply diverse reactivity for the +3 actinides and highlight the unexpected and unique AcIII chemical behaviour. PMID:27531582

  3. Discovery of the actinium, thorium, protactinium, and uranium isotopes

    CERN Document Server

    Fry, C

    2012-01-01

    Currently, 31 actinium, 31 thorium, 28 protactinium, and 23 uranium isotopes have so far been observed; the discovery of these isotopes is discussed. For each isotope a brief summary of the first refereed publication, including the production and identification method, is presented.

  4. Production of high-purity radium-223 from legacy actinium-beryllium neutron sources.

    Science.gov (United States)

    Soderquist, Chuck Z; McNamara, Bruce K; Fisher, Darrell R

    2012-07-01

    Radium-223 is a short-lived alpha-particle-emitting radionuclide with potential applications in cancer treatment. Research to develop new radiopharmaceuticals employing (223)Ra has been hindered by poor availability due to the small quantities of parent actinium-227 available world-wide. The purpose of this study was to develop innovative and cost-effective methods to obtain high-purity (223)Ra from (227)Ac. We obtained (227)Ac from two surplus actinium-beryllium neutron generators. We retrieved the actinium/beryllium buttons from the sources and dissolved them in a sulfuric-nitric acid solution. A crude actinium solid was recovered from the solution by coprecipitation with thorium fluoride, leaving beryllium in solution. The crude actinium was purified to provide about 40 milligrams of actinium nitrate using anion exchange in methanol-water-nitric acid solution. The purified actinium was then used to generate high-purity (223)Ra. We extracted (223)Ra using anion exchange in a methanol-water-nitric acid solution. After the radium was separated, actinium and thorium were then eluted from the column and dried for interim storage. This single-pass separation produces high purity, carrier-free (223)Ra product, and does not disturb the (227)Ac/(227)Th equilibrium. A high purity, carrier-free (227)Th was also obtained from the actinium using a similar anion exchange in nitric acid. These methods enable efficient production of (223)Ra for research and new alpha-emitter radiopharmaceutical development.

  5. Relativistic small-core pseudopotentials for actinium, thorium, and protactinium.

    Science.gov (United States)

    Weigand, Anna; Cao, Xiaoyan; Hangele, Tim; Dolg, Michael

    2014-04-03

    Small-core pseudopotentials for actinium, thorium, and protactinium have been energy-adjusted to multiconfiguration Dirac-Hartree-Fock reference data based on the Dirac-Coulomb-Breit Hamiltonian and the Fermi nucleus model. Corresponding optimized valence basis sets of polarized valence quadruple-ζ quality are presented. Atomic test calculations for the first four ionization potentials show satisfactory results at both the Hartree-Fock and the multireference averaged coupled-pair functional level. Highly correlated Fock-space coupled cluster calculations demonstrate that the new pseudopotentials yield ionization potentials, which are in excellent agreement with corresponding all-electron results and experimental data. The pseudopotentials and basis sets supplement a similar set previously published for uranium.

  6. Effects of spin-orbit coupling on actinium under pressure

    Energy Technology Data Exchange (ETDEWEB)

    Rubio-Ponce, A.; Rivera, J. [Departamento de Ciencias Basicas, Universidad Autonoma Metropolitana-Azcapotzalco, Mexico (Mexico); Olguin, D. [Departamento de Fi sica, Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional, Mexico (Mexico)

    2015-04-15

    Actinium (Ac) is a radioactive metal and the first element of the actinide series. At ambient conditions Ac crystallizes in the fcc lattice, however, up to date its phase diagram is unknown. In the present work, we have studied the structural and electronic properties of Ac under hydrostatic pressure assuming the fcc structure as well as three hypothetical structures, namely the hcp, bcc, and sc, and for pressures up to 100 GPa. From our calculations, we found only one structural transition allowed, from the fcc to hcp, our calculated pressure was 39.85 GPa. The calculations were performed by means of the full potential linearized augmented plane wave (FLAPW) method and the generalized gradient approximation (GGA) for the exchange-correlation energy, where we have included in our study the spin-orbit coupling which is important for heavy elements. The total energy results were fitted to the third order Birch-Murnaghan's equation of state. (copyright 2015 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  7. Production of Actinium-225 via High Energy Proton Induced Spallation of Thorium-232

    Energy Technology Data Exchange (ETDEWEB)

    Harvey, James T.; Nolen, Jerry; Vandergrift, George; Gomes, Itacil; Kroc, Tom; Horwitz, Phil; McAlister, Dan; Bowers, Del; Sullivan, Vivian; Greene, John

    2011-12-30

    The science of cancer research is currently expanding its use of alpha particle emitting radioisotopes. Coupled with the discovery and proliferation of molecular species that seek out and attach to tumors, new therapy and diagnostics are being developed to enhance the treatment of cancer and other diseases. This latest technology is commonly referred to as Alpha Immunotherapy (AIT). Actinium-225/Bismuth-213 is a parent/daughter alpha-emitting radioisotope pair that is highly sought after because of the potential for treating numerous diseases and its ability to be chemically compatible with many known and widely used carrier molecules (such as monoclonal antibodies and proteins/peptides). Unfortunately, the worldwide supply of actinium-225 is limited to about 1,000mCi annually and most of that is currently spoken for, thus limiting the ability of this radioisotope pair to enter into research and subsequently clinical trials. The route proposed herein utilizes high energy protons to produce actinium-225 via spallation of a thorium-232 target. As part of previous R and D efforts carried out at Argonne National Laboratory recently in support of the proposed US FRIB facility, it was shown that a very effective production mechanism for actinium-225 is spallation of thorium-232 by high energy proton beams. The base-line simulation for the production rate of actinium-225 by this reaction mechanism is 8E12 atoms per second at 200 MeV proton beam energy with 50 g/cm2 thorium target and 100 kW beam power. An irradiation of one actinium-225 half-life (10 days) produces {approx}100 Ci of actinium-225. For a given beam current the reaction cross section increases slightly with energy to about 400 MeV and then decreases slightly for beam energies in the several GeV regime. The object of this effort is to refine the simulations at proton beam energies of 400 MeV and above up to about 8 GeV. Once completed, the simulations will be experimentally verified using 400 MeV and 8 Ge

  8. Report for General Research September 18 to December 11, 1950 (Actinium Volume)

    Energy Technology Data Exchange (ETDEWEB)

    Haring, M.M.

    1951-01-15

    The purpose of the research work presented in this volume is to develop a process for the separation and purification of actinium-227 produced by neutron bombardment of radium-226 and to develop methods by which uniform films of actinium metal may be deposited on metallic surfaces. The design work on the cave structure and mechanical equipment used in the actinium separation is proceeding on schedule. As the mechanical design phase is nearing completion the emphasis is being directed toward processing equipment. The process as well as the mechanical equipment has been adapted from the research work of F. T. Hagemann and the Remote Control Group at Argonne National Laboratory. Consequently, one of the first objectives is to become familiary with the chemistry of the process and the operation of the mechanical equipment. Cold runs have been made on the T.T.A. benzene extraction using lanthanum and barium in place of actinium and radium. No difficulty with the operation was observed. The formation of precipitates was one of the difficulties encountered with the process as the precipitates carry radium. It has been found that metals such as nickel cause these precipitates to form and should, therefore, be avoided in the construction of equipment. it was also found that a T.T.A. solution exposed to 0.5 curie of polonium over a period of days develops a precipitate. Some new mechanical features hav eshown promise. The use of copper-coated glassware which will hold together even though the glass is cracked has made it possible to replace custom-built heaters with standard heating mantles. A new graphite, silicone grease mixture appears to hold up in stopcocks handling benzene and, as a result, may eliminate the necessary of entering the cave for regreasing. Tests on the preparation of dense concrete have given results which meet the shielding requirements for the cave. A strippable paint and tape combination has been studied and specified to provide for decontamination of

  9. Nuclear structure of $^{231}$Ac

    CERN Document Server

    Boutami, R; Mach, H; Kurcewicz, W; Fraile, L M; Gulda, K; Aas, A J; García-Raffi, L M; Løvhøiden, G; Martínez, T; Rubio, B; Taín, J L; Tengblad, O

    2008-01-01

    The low-energy structure of 231Ac has been investigated by means of gamma ray spectroscopy following the beta-decay of 231Ra. Multipolarities of 28 transitions have been established by measuring conversion electrons with a mini-orange electron spectrometer. The decay scheme of 231Ra --> 231Ac has been constructed for the first time. The Advanced Time Delayed beta-gamma-gamma(t) method has been used to measure the half-lives of five levels. The moderately fast B(E1) transition rates derived suggest that the octupole effects, albeit weak, are still present in this exotic nucleus.

  10. Analysis of the gamma spectra of the uranium, actinium, and thorium decay series

    Energy Technology Data Exchange (ETDEWEB)

    Momeni, M.H.

    1981-09-01

    This report describes the identification of radionuclides in the uranium, actinium, and thorium series by analysis of gamma spectra in the energy range of 40 to 1400 keV. Energies and absolute efficiencies for each gamma line were measured by means of a high-resolution germanium detector and compared with those in the literature. A gamma spectroscopy method, which utilizes an on-line computer for deconvolution of spectra, search and identification of each line, and estimation of activity for each radionuclide, was used to analyze soil and uranium tailings, and ore.

  11. 46 CFR 108.231 - Application.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Application. 108.231 Section 108.231 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) A-MOBILE OFFSHORE DRILLING UNITS DESIGN AND EQUIPMENT Construction and Arrangement Helicopter Facilities § 108.231 Application. Sections 108.231 through...

  12. Application of ion exchange and extraction chromatography to the separation of actinium from proton-irradiated thorium metal for analytical purposes.

    Science.gov (United States)

    Radchenko, V; Engle, J W; Wilson, J J; Maassen, J R; Nortier, F M; Taylor, W A; Birnbaum, E R; Hudston, L A; John, K D; Fassbender, M E

    2015-02-06

    Actinium-225 (t1/2=9.92d) is an α-emitting radionuclide with nuclear properties well-suited for use in targeted alpha therapy (TAT), a powerful treatment method for malignant tumors. Actinium-225 can also be utilized as a generator for (213)Bi (t1/2 45.6 min), which is another valuable candidate for TAT. Actinium-225 can be produced via proton irradiation of thorium metal; however, long-lived (227)Ac (t1/2=21.8a, 99% β(-), 1% α) is co-produced during this process and will impact the quality of the final product. Thus, accurate assays are needed to determine the (225)Ac/(227)Ac ratio, which is dependent on beam energy, irradiation time and target design. Accurate actinium assays, in turn, require efficient separation of actinium isotopes from both the Th matrix and highly radioactive activation by-products, especially radiolanthanides formed from proton-induced fission. In this study, we introduce a novel, selective chromatographic technique for the recovery and purification of actinium isotopes from irradiated Th matrices. A two-step sequence of cation exchange and extraction chromatography was implemented. Radiolanthanides were quantitatively removed from Ac, and no non-Ac radionuclidic impurities were detected in the final Ac fraction. An (225)Ac spike added prior to separation was recovered at ≥ 98%, and Ac decontamination from Th was found to be ≥ 10(6). The purified actinium fraction allowed for highly accurate (227)Ac determination at analytical scales, i.e., at (227)Ac activities of 1-100 kBq (27 nCi to 2.7 μCi). Copyright © 2014 Elsevier B.V. All rights reserved.

  13. 47 CFR 0.231 - Authority delegated.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Authority delegated. 0.231 Section 0.231... Managing Director § 0.231 Authority delegated. (a) The Managing Director, or his designee, upon securing concurrence of the General Counsel, is delegated authority to act upon requests for waiver, reduction or...

  14. 22 CFR 231.14 - Arbitration.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Arbitration. 231.14 Section 231.14 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ARAB REPUBLIC OF EGYPT LOAN GUARANTEES ISSUED UNDER THE... § 231.14 Arbitration. Any controversy or claim between USAID and any noteholder arising out of this...

  15. 42 CFR 403.231 - Emblem.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Emblem. 403.231 Section 403.231 Public Health... Provisions § 403.231 Emblem. (a) The emblem is a graphic symbol, approved by HHS, that indicates that CMS has certified a policy as meeting the requirements of the voluntary certification program, specified in §...

  16. 32 CFR 231.11 - Guidelines.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Guidelines. 231.11 Section 231.11 National... PROCEDURES GOVERNING BANKS, CREDIT UNIONS AND OTHER FINANCIAL INSTITUTIONS ON DOD INSTALLATIONS Guidelines for Application of the Privacy Act to Financial Institution Operations § 231.11 Guidelines. (a)...

  17. 39 CFR 231.1 - Responsibility.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Responsibility. 231.1 Section 231.1 Postal Service UNITED STATES POSTAL SERVICE ORGANIZATION AND ADMINISTRATION PROTECTION OF POST OFFICES § 231.1 Responsibility. (a) The protection of mail, postal funds, and property is a responsibility of every postal...

  18. 33 CFR 136.231 - Authorized claimants.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Authorized claimants. 136.231 Section 136.231 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED... PROCEDURES; DESIGNATION OF SOURCE; AND ADVERTISEMENT Procedures for Particular Claims § 136.231...

  19. 32 CFR 231.3 - Responsibilities.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Responsibilities. 231.3 Section 231.3 National... § 231.3 Responsibilities. (a) The Under Secretary of Defense (Comptroller) (USD(C)) shall develop and..., responsibility for paragraphs (g)(1) and (g)(2) of this section, to comptroller or resource management personnel...

  20. 22 CFR 231.16 - Governing law.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Governing law. 231.16 Section 231.16 Foreign... EMERGENCY WARTIME SUPPLEMENTAL APPROPRIATIONS ACT OF 2003, PUBLIC LAW 108-11-STANDARD TERMS AND CONDITIONS § 231.16 Governing law. This Guarantee shall be governed by and construed in accordance with the laws...

  1. Thorium and actinium polyphosphonate compounds as bone-seeking alpha particle-emitting agents.

    Science.gov (United States)

    Henriksen, Gjermund; Bruland, Oyvind S; Larsen, Roy H

    2004-01-01

    The present study explores the use of alpha-particle-emitting, bone-seeking agents as candidates for targeted radiotherapy. Actinium and thorium 1,4,7,10 tetraazacyclododecane N,N',N'',N''' 1,4,7,10-tetra(methylene) phosphonic acid (DOTMP) and thorium-diethylene triamine N,N',N'' penta(methylene) phosphonic acid (DTMP) were prepared and their biodistribution evaluated in conventional Balb/C mice at four hours after injection. All three bone-seeking agents showed a high uptake in bone and a low uptake in soft tissues. Among the soft tissue organs, only kidney had a relatively high uptake. The femur/kidney ratios for 227Th-DTMP, 228-Ac-DOTMP and 227Th-DOTMP were 14.2, 7.6 and 6.0, respectively. A higher liver uptake of 228Ac-DOTMP was seen than for 227Th-DTMP and 227Th-DOTMP. This suggests that some demetallation of the 228Ac-DOTMP complex had occurred. The results indicate that 225Ac-DOTMP, 227Th-DOTMP and 227Th-DTMP have promising properties as potential therapeutic bone-seeking agents.

  2. Developments towards in-gas-jet laser spectroscopy studies of actinium isotopes at LISOL

    Energy Technology Data Exchange (ETDEWEB)

    Raeder, S., E-mail: s.raeder@gsi.de [KU Leuven, Instituut voor Kern- en Stralingsfysica, Celestijnenlaan 200D, B-3001 Leuven (Belgium); Helmholtz-Institut Mainz, 55128 Mainz (Germany); GSI Helmholtzzentrum für Schwerionenforschung GmbH, Planckstraße 1, 64291 Darmstadt (Germany); Bastin, B. [GANIL, CEA/DSM-CNRS/IN2P3, B.P. 55027, 14076 Caen (France); Block, M. [Helmholtz-Institut Mainz, 55128 Mainz (Germany); GSI Helmholtzzentrum für Schwerionenforschung GmbH, Planckstraße 1, 64291 Darmstadt (Germany); Institut für Kernchemie, Johannes Gutenberg Universität, 55128 Mainz (Germany); Creemers, P. [KU Leuven, Instituut voor Kern- en Stralingsfysica, Celestijnenlaan 200D, B-3001 Leuven (Belgium); Delahaye, P. [GANIL, CEA/DSM-CNRS/IN2P3, B.P. 55027, 14076 Caen (France); Ferrer, R. [KU Leuven, Instituut voor Kern- en Stralingsfysica, Celestijnenlaan 200D, B-3001 Leuven (Belgium); Fléchard, X. [LPC Caen, ENSICAEN, Université de Caen, CNRS/IN2P3, Caen (France); Franchoo, S. [Institute de Physique Nucléaire (IPN) d’Orsay, 91406 Orsay, Cedex (France); Ghys, L. [KU Leuven, Instituut voor Kern- en Stralingsfysica, Celestijnenlaan 200D, B-3001 Leuven (Belgium); SCK-CEN, Belgian Nuclear Research Center, Boeretang 200, 2400 Mol (Belgium); Gaffney, L.P.; Granados, C. [KU Leuven, Instituut voor Kern- en Stralingsfysica, Celestijnenlaan 200D, B-3001 Leuven (Belgium); Heinke, R. [Institut für Physik, Johannes Gutenberg Universität, 55128 Mainz (Germany); Hijazi, L. [GANIL, CEA/DSM-CNRS/IN2P3, B.P. 55027, 14076 Caen (France); and others

    2016-06-01

    To study exotic nuclides at the borders of stability with laser ionization and spectroscopy techniques, highest efficiencies in combination with a high spectral resolution are required. These usually opposing requirements are reconciled by applying the in-gas-laser ionization and spectroscopy (IGLIS) technique in the supersonic gas jet produced by a de Laval nozzle installed at the exit of the stopping gas cell. Carrying out laser ionization in the low-temperature and low density supersonic gas jet eliminates pressure broadening, which will significantly improve the spectral resolution. This article presents the required modifications at the Leuven Isotope Separator On-Line (LISOL) facility that are needed for the first on-line studies of in-gas-jet laser spectroscopy. Different geometries for the gas outlet and extraction ion guides have been tested for their performance regarding the acceptance of laser ionized species as well as for their differential pumping capacities. The specifications and performance of the temporarily installed high repetition rate laser system, including a narrow bandwidth injection-locked Ti:sapphire laser, are discussed and first preliminary results on neutron-deficient actinium isotopes are presented indicating the high capability of this novel technique.

  3. Nuclear structure of {sup 231}Ac

    Energy Technology Data Exchange (ETDEWEB)

    Boutami, R. [Instituto de Estructura de la Materia, CSIC, Serrano 113 bis, E-28006 Madrid (Spain); Borge, M.J.G. [Instituto de Estructura de la Materia, CSIC, Serrano 113 bis, E-28006 Madrid (Spain)], E-mail: borge@iem.cfmac.csic.es; Mach, H. [Department of Radiation Sciences, ISV, Uppsala University, SE-751 21 Uppsala (Sweden); Kurcewicz, W. [Department of Physics, University of Warsaw, Pl-00 681 Warsaw (Poland); Fraile, L.M. [Departamento Fisica Atomica, Molecular y Nuclear, Facultad CC. Fisicas, Universidad Complutense, E-28040 Madrid (Spain); ISOLDE, PH Department, CERN, CH-1211 Geneva 23 (Switzerland); Gulda, K. [Department of Physics, University of Warsaw, Pl-00 681 Warsaw (Poland); Aas, A.J. [Department of Chemistry, University of Oslo, PO Box 1033, Blindern, N-0315 Oslo (Norway); Garcia-Raffi, L.M. [Instituto de Fisica Corpuscular, CSIC - Universidad de Valencia, Apdo. 22805, E-46071 Valencia (Spain); Lovhoiden, G. [Department of Physics, University of Oslo, PO Box 1048, Blindern, N-0316 Oslo (Norway); Martinez, T.; Rubio, B.; Tain, J.L. [Instituto de Fisica Corpuscular, CSIC - Universidad de Valencia, Apdo. 22805, E-46071 Valencia (Spain); Tengblad, O. [Instituto de Estructura de la Materia, CSIC, Serrano 113 bis, E-28006 Madrid (Spain); ISOLDE, PH Department, CERN, CH-1211 Geneva 23 (Switzerland)

    2008-10-15

    The low-energy structure of {sup 231}Ac has been investigated by means of {gamma} ray spectroscopy following the {beta}{sup -} decay of {sup 231}Ra. Multipolarities of 28 transitions have been established by measuring conversion electrons with a MINI-ORANGE electron spectrometer. The decay scheme of {sup 231}Ra {yields}{sup 231}Ac has been constructed for the first time. The Advanced Time Delayed {beta}{gamma}{gamma}(t) method has been used to measure the half-lives of five levels. The moderately fast B(E1) transition rates derived suggest that the octupole effects, albeit weak, are still present in this exotic nucleus.

  4. 27 CFR 25.231 - Finished beer.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Finished beer. 25.231... OF THE TREASURY LIQUORS BEER Beer Purchased From Another Brewer § 25.231 Finished beer. (a) A brewer may obtain beer in barrels and kegs, finished and ready for sale from another brewer. The purchasing...

  5. 40 CFR 231.5 - Recommended determination.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Recommended determination. 231.5... 404(c) PROCEDURES § 231.5 Recommended determination. (a) The Regional Administrator or his designee... public notice of the proposed determination, either withdraw the proposed determination or prepare a...

  6. 22 CFR 231.03 - The Guarantee.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false The Guarantee. 231.03 Section 231.03 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ARAB REPUBLIC OF EGYPT LOAN GUARANTEES ISSUED UNDER THE... maintained by the Fiscal Agent....

  7. 34 CFR 668.231 - Definitions.

    Science.gov (United States)

    2010-07-01

    ..., eligible for special education and related services under the Individuals with Disabilities Education Act... 34 Education 3 2010-07-01 2010-07-01 false Definitions. 668.231 Section 668.231 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY...

  8. 40 CFR 436.231 - Specialized definitions.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Specialized definitions. 436.231 Section 436.231 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS MINERAL MINING AND PROCESSING POINT SOURCE CATEGORY Magnesite Subcategory §...

  9. 32 CFR 231.2 - Policy.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Policy. 231.2 Section 231.2 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS PROCEDURES... Policy. The policy pertaining to financial institutions operating on DoD installations is contained in...

  10. Dicty_cDB: VSC231 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available VS (Link to library) VSC231 (Link to dictyBase) - - - Contig-U12227-1 VSC231Z (Link... to Original site) - - VSC231Z 521 - - - - Show VSC231 Library VS (Link to library) Clone ID VSC231 (Link to...ycdb.biol.tsukuba.ac.jp/CSM/VS/VSC2-B/VSC231Q.Seq.d/ Representative seq. ID VSC23...1Z (Link to Original site) Representative DNA sequence >VSC231 (VSC231Q) /CSM/VS/VSC2-B/VSC231Q.Seq.d/ XXXXX... E Sequences producing significant alignments: (bits) Value VSC231 (VSC231Q) /CSM/VS/VSC2-B/VSC

  11. 48 CFR 252.231-7000 - Supplemental cost principles.

    Science.gov (United States)

    2010-10-01

    ... principles. 252.231-7000 Section 252.231-7000 Federal Acquisition Regulations System DEFENSE ACQUISITION... of Provisions And Clauses 252.231-7000 Supplemental cost principles. As prescribed in 231.100-70, use the following clause: Supplemental Cost Principles (DEC 1991) When the allowability of costs...

  12. Safety analysis report 231-Z Building

    Energy Technology Data Exchange (ETDEWEB)

    Powers, C.S.

    1989-03-01

    This report provides an intensive review of the nuclear safety of the operation of the 231-Z Building. For background information complete descriptions of the floor plan, building services, alarm systems, and glove box systems are included in this report. In addition, references are included to The Plutonium Laboratory Radiation Work Procedures, Safety Guides, 231-Z Operating Procedures Manual and Nuclear Materials accountability Procedures. Engineered and administrative features contribute to the overall safety of personnel, the building, and environs. The consequences of credible incidents were considered and are discussed.

  13. 12 CFR 231.2 - Definitions.

    Science.gov (United States)

    2010-01-01

    ... ELIGIBILITY FOR FINANCIAL INSTITUTION (REGULATION EE) § 231.2 Definitions. As used in this part, unless the...” contract). (d) Financial market means a market for a financial contract. (e) Gross mark-to-market positions... other person that controls, is controlled by, or is under common control with the person. (c)...

  14. 28 CFR 23.1 - Purpose.

    Science.gov (United States)

    2010-07-01

    ... Administration DEPARTMENT OF JUSTICE CRIMINAL INTELLIGENCE SYSTEMS OPERATING POLICIES § 23.1 Purpose. The purpose of this regulation is to assure that all criminal intelligence systems operating through support...-647), are utilized in conformance with the privacy and constitutional rights of individuals....

  15. 22 CFR 231.07 - Fiscal Agent obligations.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Fiscal Agent obligations. 231.07 Section 231.07 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ARAB REPUBLIC OF EGYPT LOAN GUARANTEES ISSUED UNDER... CONDITIONS § 231.07 Fiscal Agent obligations. Failure of the Fiscal Agent to perform any of its...

  16. 48 CFR 231.205-22 - Legislative lobbying costs.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Legislative lobbying costs. 231.205-22 Section 231.205-22 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS... Contracts With Commercial Organizations 231.205-22 Legislative lobbying costs. (a) Costs associated...

  17. 36 CFR 2.31 - Trespassing, tampering and vandalism.

    Science.gov (United States)

    2010-07-01

    ... vandalism. 2.31 Section 2.31 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR RESOURCE PROTECTION, PUBLIC USE AND RECREATION § 2.31 Trespassing, tampering and vandalism. (a..., except when such property is under one's lawful control or possession. (3) Vandalism. Destroying...

  18. 48 CFR 231.205-6 - Compensation for personal services.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Compensation for personal services. 231.205-6 Section 231.205-6 Federal Acquisition Regulations System DEFENSE ACQUISITION... PROCEDURES Contracts With Commercial Organizations 231.205-6 Compensation for personal services. (f)(1)...

  19. 49 CFR 231.20 - Variation in size permitted.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Variation in size permitted. 231.20 Section 231.20..., DEPARTMENT OF TRANSPORTATION RAILROAD SAFETY APPLIANCE STANDARDS § 231.20 Variation in size permitted. To... total variation of 5 percent below size given is permitted....

  20. 49 CFR 384.231 - Satisfaction of State disqualification requirement.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 5 2010-10-01 2010-10-01 false Satisfaction of State disqualification requirement. 384.231 Section 384.231 Transportation Other Regulations Relating to Transportation (Continued... Compliance by States § 384.231 Satisfaction of State disqualification requirement. (a) Applicability....

  1. The release of dissolved actinium to the ocean: A global comparison of different end-members

    Science.gov (United States)

    Geibert, W.; Charette, M.; Kim, G.; Moore, W.S.; Street, J.; Young, M.; Paytan, A.

    2008-01-01

    The measurement of short-lived 223Ra often involves a second measurement for supported activities, which represents 227Ac in the sample. Here we exploit this fact, presenting a set of 284 values on the oceanic distribution of 227Ac, which was collected when analyzing water samples for short-lived radium isotopes by the radium delayed coincidence counting system. The present work compiles 227Ac data from coastal regions all over the northern hemisphere, including values from ground water, from estuaries and lagoons, and from marine end-members. Deep-sea samples from a continental slope off Puerto Rico and from an active vent site near Hawaii complete the overview of 227Ac near its potential sources. The average 227Ac activities of nearshore marine end-members range from 0.4??dpm m- 3 at the Gulf of Mexico to 3.0??dpm m- 3 in the coastal waters of the Korean Strait. In analogy to 228Ra, we find the extension of adjacent shelf regions to play a substantial role for 227Ac activities, although less pronounced than for radium, due to its weaker shelf source. Based on previously published values, we calculate an open ocean 227Ac inventory of 1.35 * 1018??dpm 227Acex in the ocean, which corresponds to 37??moles, or 8.4??kg. This implies a flux of 127??dpm m-2 y- 1 from the deep-sea floor. For the shelf regions, we obtain a global inventory of 227Ac of 4.5 * 1015??dpm, which cannot be converted directly into a flux value, as the regional loss term of 227Ac to the open ocean would have to be included. Ac has so far been considered to behave similarly to Ra in the marine environment, with the exception of a strong Ac source in the deep-sea due to 231Paex. Here, we present evidence of geochemical differences between Ac, which is retained in a warm vent system, and Ra, which is readily released [Moore, W.S., Ussler, W. and Paull, C.K., 2008-this issue. Short-lived radium isotopes in the Hawaiian margin: Evidence for large fluid fluxes through the Puna Ridge. Marine Chemistry

  2. 49 CFR 231.22 - Operation of track motor cars.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Operation of track motor cars. 231.22 Section 231... motor cars. On and after August 1, 1963, it shall be unlawful for any railroad subject to the requirements of the Safety Appliance Acts to operate or permit to be operated on its line track motor cars...

  3. 22 CFR 231.06 - Transferability of Guarantee; Note Register.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Transferability of Guarantee; Note Register. 231.06 Section 231.06 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ARAB REPUBLIC OF EGYPT... required to be maintained by the Fiscal Agent pursuant to the Fiscal Agency Agreement. USAID shall...

  4. 48 CFR 231.205-70 - External restructuring costs.

    Science.gov (United States)

    2010-10-01

    ... companies not previously under common ownership or control are combined, whether by merger, acquisition, or... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false External restructuring costs. 231.205-70 Section 231.205-70 Federal Acquisition Regulations System DEFENSE ACQUISITION...

  5. 49 CFR 192.231 - Protection from weather.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Protection from weather. 192.231 Section 192.231 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY... weather. The welding operation must be protected from weather conditions that would impair the quality...

  6. 48 CFR 1852.231-71 - Determination of compensation reasonableness.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Determination of compensation reasonableness. 1852.231-71 Section 1852.231-71 Federal Acquisition Regulations System NATIONAL... Contract Act employees proposed that do not fail within the scope of any classification listed in...

  7. 12 CFR 231.3 - Qualification as a financial institution.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Qualification as a financial institution. 231.3... RESERVE SYSTEM NETTING ELIGIBILITY FOR FINANCIAL INSTITUTION (REGULATION EE) § 231.3 Qualification as a financial institution. (a) A person qualifies as a financial institution for purposes of sections 401-407 of...

  8. 48 CFR 1352.231-71 - Duplication of effort.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Duplication of effort. 1352.231-71 Section 1352.231-71 Federal Acquisition Regulations System DEPARTMENT OF COMMERCE CLAUSES... Duplication of effort. As prescribed in 48 CFR 1331.205-70, insert the following clause: Duplication of...

  9. 14 CFR 417.231 - Collision avoidance analysis.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Collision avoidance analysis. 417.231..., DEPARTMENT OF TRANSPORTATION LICENSING LAUNCH SAFETY Flight Safety Analysis § 417.231 Collision avoidance analysis. (a) General. A flight safety analysis must include a collision avoidance analysis...

  10. [231 laparoscopic cholecystectomy in ambulatory: what results?].

    Science.gov (United States)

    Goulart, André; Delgado, Margarida; Antunes, Maria Conceição; Braga Dos Anjos, João

    2013-01-01

    Introdução: A colecistectomia laparoscópica é actualmente o gold standard no tratamento da patologia litiásica vesicular e colecistite aguda. A sua realização em regime de cirurgia de ambulatório permanece em discussão. O presente estudo tem por objectivo analisar a qualidade e segurança das colecistectomias laparoscópicas realizadas pela Unidade de Cirurgia de Ambulatório do Hospital de Braga e comparar os resultados com outros centros europeus que realizam colecistectomia laparoscópica em regime de ambulatório.Material e Métodos: Estudo observacional prospectivo de doentes submetidos a colecistectomia laparoscópica em regime de ambulatório durante 26 meses. Foram recolhidos dados referentes à demografia do doente, complicações peri e pós-operatórias, tempo cirúrgico e tempo de permanência no recobro e internamentos não programados.Resultados: Foram submetidos a colecistectomia laparoscópica em regime de ambulatório com pernoita (alta < 24h) 231 doentes. Três doentes tiveram intercorrências intra-operatórias com necessidade de conversão para laparotomia e quatro doentes foram internados após a cirurgia. O tempo médio de cirurgia foi de 58 minutos e o tempo médio de recobro de 19h19m. A morbilidade pósoperatória foi de 7,8% tendo, ocorrido dois internamentos não programados.Discussão: Uma das discussões que existe em torno da colecistectomia laparoscópica em regime de ambulatório é a necessidade de vigilância hospitalar durante a primeira noite após a cirurgia. Na nossa unidade, iniciamos a realização da colecistectomia laparoscópica em regime de ambulatório com pernoita hospitalar. Os resultados de mais de dois anos e 231 doentes operados a colecistectomia laparoscópica mostram que é uma técnica perfeitamente segura em regime de ambulatório.Conclusões: Os dados do estudo mostram que a colecistectomia laparoscópica é uma técnica segura em regime de ambulatório, com resultados semelhantes comparativamente com

  11. Meningoencefalite tuberculosa: avaliação de 231 casos Tuberculosis meningoencephalitis: exposure of 231 cases

    OpenAIRE

    1998-01-01

    Neste estudo foram avaliados 231 pacientes com meningoencefalite tuberculosa, sendo que 62 casos tiveram diagnóstico comprovado e 169 apresentavam quadro clínico e laboratorial compatíveis com este diagnóstico. Foram 127 (55%) pacientes do sexo masculino, a idade variou de 1 mês a 68 anos, com 97 (42%) na faixa etária igual ou inferior a um ano. As características clínicas, demográficas e liquóricas foram estudadas e comparadas entre os casos confirmados e os de diagnóstico provável. Em concl...

  12. VLBI observations of the CSO Source Mrk 231

    Science.gov (United States)

    Tamura, S.; Murata, Y.; Asada, K.

    2009-08-01

    We present the images of Mrk 231 using VSOP and VLBA archival data. Mrk 231 is one of the nearby objects with a developed radio lobe at parsec-scales, and is categorized as a Compact Symmetric Object (CSO). These images allows us to estimate the age of last Mrk 231 outburst using three different methods: kinematic aging, the synchrotron aging and an adiabatic cooling model aging. With kinematic aging, we derived upper limit of the proper motion of 0.47 c, which gives the lower limit for the age of 170 yrs.

  13. Phenotype abnormality: 231 [Arabidopsis Phenome Database[Archive

    Lifescience Database Archive (English)

    Full Text Available 231 http://metadb.riken.jp/db/SciNetS_ria224i/cria224u1ria224u737i decreased speed... in organ named seedling during process named growth ... seedling ... decreased speed ... growth ...

  14. 49 CFR 231.21 - Tank cars without underframes.

    Science.gov (United States)

    2010-10-01

    ... to prevent sagging. (c) Sill steps. Same as specified for “Box and other house cars” (see § 231.1(d.... (ii) The operating platforms shall be supported to prevent sagging and be securely attached to...

  15. Meningoencefalite tuberculosa: avaliação de 231 casos Tuberculosis meningoencephalitis: exposure of 231 cases

    Directory of Open Access Journals (Sweden)

    Ceuci Nunes

    1998-10-01

    Full Text Available Neste estudo foram avaliados 231 pacientes com meningoencefalite tuberculosa, sendo que 62 casos tiveram diagnóstico comprovado e 169 apresentavam quadro clínico e laboratorial compatíveis com este diagnóstico. Foram 127 (55% pacientes do sexo masculino, a idade variou de 1 mês a 68 anos, com 97 (42% na faixa etária igual ou inferior a um ano. As características clínicas, demográficas e liquóricas foram estudadas e comparadas entre os casos confirmados e os de diagnóstico provável. Em conclusão reafirmamos a gravidade desta doença, com altas taxas de letalidade principalmente na faixa etária de zero a quatro anos e a possibilidade de erros diagnósticos nas apresentações com formas agudas e predominância de neutrófilos no líquor.This study assessed 231 cases of tuberculous meningitis of which 62 (26.8% had diagnostic confirmation against 169 (73.2% with only clinical picture and laboratorial indication for this diagnosis. Fifty-five percent of the sample was male; ages ranged from one month to 68 years, 42% comprising children below four years.Clinical, demographic and liquoric characteristics were investigated and compared amongst those with likely and confirmed diagnosis. In conclusion, atention is drawn to the severity of this desease with high rates of lethality mainly within the age-range of 0-4 years, and to the possibility of misdiagnosis in the presentation of acute forms and predominance of neutrophils in the liquor.

  16. 231Pa systematics in postglacial volcanic rocks from Iceland

    Science.gov (United States)

    Turner, Simon; Kokfelt, Thomas; Hoernle, Kaj; Lundstrom, Craig; Hauff, Folkmar

    2016-07-01

    Several recent studies have highlighted the potential of combined 238U-230Th and 235U-231Pa systematics to constrain upwelling rates and the role of recycled mafic lithologies in mantle plume-derived basalts. Accordingly, we present measurements of the 231Pa concentrations from 26 mafic volcanic rocks from Iceland, including off-axis basalts from the Snaefellsnes Peninsula, to complement previously published 238U-230Th-226Ra data. 231Pa concentrations vary from 27 to 624 fg/g and (231Pa/235U) ratios from 1.12 to 2.11 with the exception of one anomalous sample from the Southeast Rift which has a 231Pa deficit with (231Pa/235U) = 0.86. An important new result is that basalts from the Southeast Rift and the Snaefellsnes Peninsula define a trend at relatively low (231Pa/235U) for a given (230Th/238U) ratio. Many of the remaining samples fall in or around the global field for ocean island basalts but those from the Mid-Iceland Belt and the Southwest Rift/Reykjanes Peninsula extend to higher (231Pa/235U) ratios at a given (230Th/238U), similar to mid-ocean ridge basalts. In principle, these lavas could result from melting of peridotite at lower pressures. However, there is no reason to suspect that the Mid-Iceland Belt and the Southwest Rift lavas reflect shallower melting than elsewhere in Iceland. In our preferred model, these lavas reflect melting of garnet peridotite whereas those from the Southeast Rift and the Snaefellsnes Peninsula contain a significant contribution (up to 20%) of melt from garnet pyroxenite. This is consistent with incompatible trace element and radiogenic isotope evidence for recycled oceanic crust in these lavas. There is increasing agreement that the displacement of ocean island basalts to lower (231Pa/235U) ratios at a given (230Th/238U), compared to mid-ocean ridge basalts, reflects the role of recycled mafic lithologies such as garnet pyroxenite as well as higher average pressures of melting. It now seems likely that this interpretation may

  17. Mutations in TMEM231 cause Meckel-Gruber syndrome.

    Science.gov (United States)

    Shaheen, Ranad; Ansari, Shinu; Mardawi, Elham Al; Alshammari, Muneera J; Alkuraya, Fowzan S

    2013-03-01

    Meckel-Gruber syndrome (MKS) is a genetically heterogeneous severe ciliopathy characterised by early lethality, occipital encephalocele, polydactyly, and polycystic kidney disease. To report genetic analysis results in two families in which all known MKS diseases genes have been excluded. In two consanguineous families with classical MKS in which autozygome-guided sequencing of previously reported MKS genes was negative, we performed exome sequencing followed by autozygome filtration. We identified one novel splicing mutation in TMEM231, which led to complete degradation of the mutant transcript in one family, and a novel missense mutation in the other, both in the homozygous state. TMEM231 represents a novel MKS locus. The very recent identification of TMEM231 mutations in Joubert syndrome supports the growing appreciation of the overlap in the molecular pathogenesis between these two ciliopathies.

  18. Mutations in TMEM231 cause Meckel–Gruber syndrome

    Science.gov (United States)

    Shaheen, Ranad; Ansari, Shinu; Mardawi, Elham AL; Alshammari, Muneera J; Alkuraya, Fowzan S

    2013-01-01

    Background Meckel–Gruber syndrome (MKS) is a genetically heterogeneous severe ciliopathy characterised by early lethality, occipital encephalocele, polydactyly, and polycystic kidney disease. Purpose To report genetic analysis results in two families in which all known MKS diseases genes have been excluded. Methods In two consanguineous families with classical MKS in which autozygome-guided sequencing of previously reported MKS genes was negative, we performed exome sequencing followed by autozygome filtration. Results We identified one novel splicing mutation in TMEM231, which led to complete degradation of the mutant transcript in one family, and a novel missense mutation in the other, both in the homozygous state. Conclusions TMEM231 represents a novel MKS locus. The very recent identification of TMEM231 mutations in Joubert syndrome supports the growing appreciation of the overlap in the molecular pathogenesis between these two ciliopathies. PMID:23349226

  19. 32 CFR Appendix A to Part 231 - Sample Operating Agreement

    Science.gov (United States)

    2010-07-01

    ... the DoD 7000.14-R (as codified in the Code of Federal Regulations (CFR) at 32 CFR parts 230 and 231... requirements in Volume 5, Chapter 34, of DoD 7000.14-R, as codified in the Code of Federal Regulations (CFR... programs, financial management program and newcomer's briefings. g. Prominently post in the lobby of...

  20. 27 CFR 40.231 - Consumption by employees.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Consumption by employees... Products § 40.231 Consumption by employees. A manufacturer of tobacco products may gratuitously furnish tobacco products, without determination and payment of tax, for personal consumption by employees in...

  1. 12 CFR 231.1 - Authority, purpose, and scope.

    Science.gov (United States)

    2010-01-01

    ... markets. This part expands the Act's definition of “financial institution” to allow more financial market... SYSTEM NETTING ELIGIBILITY FOR FINANCIAL INSTITUTION (REGULATION EE) § 231.1 Authority, purpose, and.... 4401-4407). This part does not affect the status of those financial institutions specifically...

  2. Herschel observations of water vapour in Markarian 231

    NARCIS (Netherlands)

    González-Alfonso, E.; Fischer, J.; Isaak, K.; Rykala, A.; Savini, G.; Spaans, M.; van der Werf, P.; Meijerink, R.; Israel, F. P.; Loenen, A. F.; Vlahakis, C.; Smith, H. A.; Charmandaris, V.; Aalto, S.; Henkel, C.; Weiß, A.; Walter, F.; Greve, T. R.; Martín-Pintado, J.; Naylor, D. A.; Spinoglio, L.; Veilleux, S.; Harris, A. I.; Armus, L.; Lord, S.; Mazzarella, J.; Xilouris, E. M.; Sanders, D. B.; Dasyra, K. M.; Wiedner, M. C.; Kramer, C.; Papadopoulos, P. P.; Stacey, G. J.; Evans, A. S.; Gao, Y.

    2010-01-01

    The Ultra luminous infrared galaxy (ULIRG) Mrk 231 reveals up to seven rotational lines of water (H2O) in emission, including a very high-lying (Eupper = 640 K) line detected at a 4σ level, within the Herschel/SPIRE wavelength range (190 <λ (μm) <640), whereas PACS observations show one H2O line at

  3. Herschel observations of water vapour in Markarian 231

    NARCIS (Netherlands)

    Gonzalez-Alfonso, E.; Fischer, J.; Isaak, K.; Rykala, A.; Savini, G.; Spaans, M.; Meijerink, R.; Israel, F. P.; Loenen, A. F.; Vlahakis, C.; Smith, H. A.; Charmandaris, V.; Aalto, S.; Henkel, C.; Weiss, A.; Walter, F.; Greve, T. R.; Martin-Pintado, J.; Naylor, D. A.; Spinoglio, L.; Veilleux, S.; Harris, A. I.; Armus, L.; Lord, S.; Mazzarella, J.; Xilouris, E. M.; Sanders, D. B.; Dasyra, K. M.; Wiedner, M. C.; Kramer, C.; Papadopoulos, P. P.; Stacey, G. J.; Evans, A. S.; Gao, Y.; van der Werf, Paul P.

    2010-01-01

    The Ultra luminous infrared galaxy (ULIRG) Mrk 231 reveals up to seven rotational lines of water (H(2)O) in emission, including a very high-lying (Eupper = 640 K) line detected at a 4 sigma level, within the Herschel/SPIRE wavelength range (190

  4. 18 CFR 367.2310 - Account 231, Notes payable.

    Science.gov (United States)

    2010-04-01

    ... payable. This account must include the face value of all notes, drafts, acceptances, or other similar... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Account 231, Notes payable. 367.2310 Section 367.2310 Conservation of Power and Water Resources FEDERAL ENERGY...

  5. 49 CFR 231.0 - Applicability and penalties.

    Science.gov (United States)

    2010-10-01

    ..., DEPARTMENT OF TRANSPORTATION RAILROAD SAFETY APPLIANCE STANDARDS § 231.0 Applicability and penalties. (a... of the coupling is not more than 25 inches. (5) A locomotive used in hauling a train referred to in paragraph (b)(4) of this section when the locomotive and cars of the train are used only to transport...

  6. 49 CFR 231.29 - Road locomotives with corner stairways.

    Science.gov (United States)

    2010-10-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD SAFETY APPLIANCE STANDARDS § 231.29 Road locomotives with corner stairways. After September 30, 1979, road locomotives with corner stairway openings must be... 49 Transportation 4 2010-10-01 2010-10-01 false Road locomotives with corner stairways....

  7. Opportunistic infections and malignancies in 231 Danish AIDS patients

    DEFF Research Database (Denmark)

    Pedersen, C; Gerstoft, J; Tauris, P;

    1990-01-01

    We analysed cumulative disease frequencies in the first 231 adult Danish AIDS patients with life tables. There was a certain hierarchical pattern in the occurrence of complicating diseases. Herpes zoster, Kaposi's sarcoma and Pneumocystis carinii pneumonia were early manifestations, whereas...... diseases caused by cytomegalovirus and atypical mycobacteria tended to occur later in the course of AIDS. Compared with all other AIDS patients, homosexual men were more likely to develop Kaposi's sarcoma, cytomegalovirus chorioretinitis and mucocutaneous herpes simplex virus infection. The proportion...

  8. Period of Light Variability in BL Lac ON 231

    Indian Academy of Sciences (India)

    Xu Yun Bing; Zhang Hao Jing; Zhang Xiong; Mao Wei Ming; Dong Fu Tong

    2011-03-01

    In this paper, the authors have compiled the data of about 100 years in B-band of the BL Lac ON 231 and used this database to analyze periodicity signals in the optical light curve. Two different methods were applied: the wavelet analysis and the Discrete Correlation Function (DCF) method. We revealed the existence of periods of 13.5 years in the source variability.

  9. 5 CFR 9901.231 - Conversion of positions and employees to NSPS classification system.

    Science.gov (United States)

    2010-01-01

    ... NSPS classification system. 9901.231 Section 9901.231 Administrative Personnel DEPARTMENT OF DEFENSE... MANAGEMENT) DEPARTMENT OF DEFENSE NATIONAL SECURITY PERSONNEL SYSTEM (NSPS) Classification Transitional Provisions § 9901.231 Conversion of positions and employees to NSPS classification system. (a)...

  10. 5 CFR 9701.231 - Conversion of positions and employees to the DHS classification system.

    Science.gov (United States)

    2010-01-01

    ... the DHS classification system. 9701.231 Section 9701.231 Administrative Personnel DEPARTMENT OF... MANAGEMENT) DEPARTMENT OF HOMELAND SECURITY HUMAN RESOURCES MANAGEMENT SYSTEM Classification Transitional Provisions § 9701.231 Conversion of positions and employees to the DHS classification system. (a)...

  11. 32 CFR Appendix B to Part 231 - In-Store Banking

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false In-Store Banking B Appendix B to Part 231.... 231, App. B Appendix B to Part 231—In-Store Banking A. Selection Process. The purpose of this guidance... provide in-store banking services when such services are desired and approved by the installation...

  12. 27 CFR 31.231 - Destruction of marks and brands on wine containers.

    Science.gov (United States)

    2010-04-01

    ... brands on wine containers. 31.231 Section 31.231 Alcohol, Tobacco Products and Firearms ALCOHOL AND... § 31.231 Destruction of marks and brands on wine containers. A dealer who empties any cask, barrel, keg, or other bulk container of wine must scrape or obliterate from the empty container all marks,...

  13. 22 CFR 23.1 - Remittances made payable to the Department of State.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Remittances made payable to the Department of State. 23.1 Section 23.1 Foreign Relations DEPARTMENT OF STATE FEES AND FUNDS FINANCE AND ACCOUNTING § 23.1 Remittances made payable to the Department of State. Except as otherwise specified in this...

  14. File list: Oth.Brs.05.AllAg.MDA-MB-231 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Brs.05.AllAg.MDA-MB-231 hg19 TFs and others Breast MDA-MB-231 SRX883585,SRX8835...473,SRX1156472,SRX1076936 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Brs.05.AllAg.MDA-MB-231.bed ...

  15. File list: Unc.Brs.20.AllAg.MDA-MB-231 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Brs.20.AllAg.MDA-MB-231 hg19 Unclassified Breast MDA-MB-231 SRX101819,SRX101822...,SRX101820,SRX265431,SRX101825,SRX101821 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Brs.20.AllAg.MDA-MB-231.bed ...

  16. File list: His.Brs.20.AllAg.MDA-MB-231 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Brs.20.AllAg.MDA-MB-231 hg19 Histone Breast MDA-MB-231 SRX891828,SRX332676,SRX8...X332674,SRX891827,SRX196427 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Brs.20.AllAg.MDA-MB-231.bed ...

  17. File list: Oth.Brs.20.AllAg.MDA-MB-231 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Brs.20.AllAg.MDA-MB-231 hg19 TFs and others Breast MDA-MB-231 SRX883577,SRX8835...472,SRX1044416,SRX1044414 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Brs.20.AllAg.MDA-MB-231.bed ...

  18. File list: ALL.Brs.05.AllAg.MDA-MB-231 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Brs.05.AllAg.MDA-MB-231 hg19 All antigens Breast MDA-MB-231 SRX332679,SRX883585...,SRX1156475 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Brs.05.AllAg.MDA-MB-231.bed ...

  19. File list: ALL.Brs.10.AllAg.MDA-MB-231 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Brs.10.AllAg.MDA-MB-231 hg19 All antigens Breast MDA-MB-231 SRX883577,SRX883579...,SRX1156475 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Brs.10.AllAg.MDA-MB-231.bed ...

  20. File list: Unc.Brs.50.AllAg.MDA-MB-231 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Brs.50.AllAg.MDA-MB-231 hg19 Unclassified Breast MDA-MB-231 SRX101819,SRX101822...,SRX101820,SRX101825,SRX265431,SRX101821 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Brs.50.AllAg.MDA-MB-231.bed ...

  1. File list: Unc.Brs.05.AllAg.MDA-MB-231 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Brs.05.AllAg.MDA-MB-231 hg19 Unclassified Breast MDA-MB-231 SRX101820,SRX265431...,SRX101819,SRX101822,SRX101821,SRX101825 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Brs.05.AllAg.MDA-MB-231.bed ...

  2. File list: His.Brs.50.AllAg.MDA-MB-231 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Brs.50.AllAg.MDA-MB-231 hg19 Histone Breast MDA-MB-231 SRX891828,SRX332676,SRX8...X196427,SRX196428,SRX246864 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Brs.50.AllAg.MDA-MB-231.bed ...

  3. File list: Unc.Brs.10.AllAg.MDA-MB-231 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Brs.10.AllAg.MDA-MB-231 hg19 Unclassified Breast MDA-MB-231 SRX265431,SRX101819...,SRX101822,SRX101820,SRX101825,SRX101821 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Brs.10.AllAg.MDA-MB-231.bed ...

  4. File list: Oth.Brs.10.AllAg.MDA-MB-231 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Brs.10.AllAg.MDA-MB-231 hg19 TFs and others Breast MDA-MB-231 SRX883577,SRX8835...913,SRX1076936,SRX1156472 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Brs.10.AllAg.MDA-MB-231.bed ...

  5. File list: ALL.Brs.20.AllAg.MDA-MB-231 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Brs.20.AllAg.MDA-MB-231 hg19 All antigens Breast MDA-MB-231 SRX883577,SRX883576...0,SRX246863 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Brs.20.AllAg.MDA-MB-231.bed ...

  6. File list: His.Brs.05.AllAg.MDA-MB-231 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Brs.05.AllAg.MDA-MB-231 hg19 Histone Breast MDA-MB-231 SRX332679,SRX332678,SRX8...X332675,SRX891830,SRX196428 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Brs.05.AllAg.MDA-MB-231.bed ...

  7. File list: ALL.Brs.50.AllAg.MDA-MB-231 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Brs.50.AllAg.MDA-MB-231 hg19 All antigens Breast MDA-MB-231 SRX883577,SRX883576...4,SRX737089 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Brs.50.AllAg.MDA-MB-231.bed ...

  8. File list: Oth.Brs.50.AllAg.MDA-MB-231 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Brs.50.AllAg.MDA-MB-231 hg19 TFs and others Breast MDA-MB-231 SRX883577,SRX8835...416,SRX1044415,SRX1044414 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Brs.50.AllAg.MDA-MB-231.bed ...

  9. File list: His.Brs.10.AllAg.MDA-MB-231 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Brs.10.AllAg.MDA-MB-231 hg19 Histone Breast MDA-MB-231 SRX332679,SRX332678,SRX8...X332674,SRX332675,SRX196428 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Brs.10.AllAg.MDA-MB-231.bed ...

  10. 29 CFR 779.231 - Franchise arrangements which do not create a larger enterprise.

    Science.gov (United States)

    2010-07-01

    ... enterprise. 779.231 Section 779.231 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION... Apply; Enterprise Coverage Leased Departments, Franchise and Other Business Arrangements § 779.231 Franchise arrangements which do not create a larger enterprise. (a) While it is clear that in every...

  11. A Blazar-Like Radio Flare in Mrk 231

    CERN Document Server

    Reynolds, Cormac; O'Dea, Christopher; Hurley-Walker, Natasha; Wrobel, Joan

    2013-01-01

    Radio monitoring of the broad absorption line quasar (BALQSO) Mrk 231 from 13.9 GHz to 17.6 GHz detected a strong flat spectrum flare. Even though BALQSOs are typically weak radio sources, the 17.6 GHz flux density doubled in ~150 days, from ~135 mJy to ~270 mJy. It is demonstrated that the elapsed rise time in the quasar rest frame and the relative magnitude of the flare is typical of some of the stronger flares in blazars that are associated with the ejection of discrete components on parsec scales. The decay of a similar flare was found in a previous monitoring campaign at 22 GHz. We conclude that these flares are not rare and indicate the likely ejection of a new radio component that can be resolved from the core with Very Long Baseline Interferometry. The implication is that Mrk 231 seems to be a quasar in which the physical mechanism that produces the BAL wind is in tension with the emergence of a fledgling blazar.

  12. Loquat (Eriobotrya japonica) leaf extract inhibits the growth of MDA-MB-231 tumors in nude mouse xenografts and invasion of MDA-MB-231 cells.

    Science.gov (United States)

    You, Mi-Kyoung; Kim, Min-Sook; Jeong, Kyu-Shik; Kim, Eun; Kim, Yong-Jae; Kim, Hyeon-A

    2016-04-01

    The present study was conducted to examine the inhibitory effect of loquat leaves on MDA-MB-231 cell proliferation and invasion. Female athymic nude mice were given a subcutaneous (s.c.) inoculation of MDA-MB-231 cells and randomly grouped to receive a s.c. injection of either 500 mg/kg ethanol, water extract or vehicle five times a week. Tumor growth, mitotic rate and necrosis were examined. MDA-MB-231 cells were cultured with DMSO or with various concentrations of loquat water or ethanol extract. Proliferation, adhesion, migration, invasion and matrix metalloproteinase (MMP) activity were examined. Tumor growth of xenograft nude mouse was significantly reduced by loquat extracts. The results of mitotic examination revealed that loquat extracts reduced tumor cell division. Both ethanol and water extracts significantly inhibited MDA-MB-231 cell proliferation. The protein expression of ErbB3 was significantly down-regulated by loquat leaf extracts. Loquat leaf extracts increased apoptosis of MDA-MB-231 cells following 24 hour incubation and the ethanol extract was more potent in inducing apoptosis than the water extract. Furthermore, loquat extracts inhibited adhesion, migration and invasion of MDA-MB-231 cells. MMP activity was significantly inhibited by loquat extracts. Our results show that extracts of loquat inhibit the growth of tumor in MDA-MB-231 xenograft nude mice and the invasion of human breast cancer cells, indicating the inhibition of tumor cell proliferation and invasion.

  13. Opportunistic infections and malignancies in 231 Danish AIDS patients

    DEFF Research Database (Denmark)

    Pedersen, C; Gerstoft, J; Tauris, P;

    1990-01-01

    We analysed cumulative disease frequencies in the first 231 adult Danish AIDS patients with life tables. There was a certain hierarchical pattern in the occurrence of complicating diseases. Herpes zoster, Kaposi's sarcoma and Pneumocystis carinii pneumonia were early manifestations, whereas...... diseases caused by cytomegalovirus and atypical mycobacteria tended to occur later in the course of AIDS. Compared with all other AIDS patients, homosexual men were more likely to develop Kaposi's sarcoma, cytomegalovirus chorioretinitis and mucocutaneous herpes simplex virus infection. The proportion...... of patients who developed particular diseases changed with calendar time. Most striking was a three to fourfold decrease in diseases caused by cytomegalovirus. In conclusion, the study showed that disease frequencies in patients with AIDS may vary with the patients risk behaviour and duration of AIDS...

  14. Opportunistic infections and malignancies in 231 Danish AIDS patients

    DEFF Research Database (Denmark)

    Pedersen, C; Gerstoft, J; Tauris, P

    1990-01-01

    We analysed cumulative disease frequencies in the first 231 adult Danish AIDS patients with life tables. There was a certain hierarchical pattern in the occurrence of complicating diseases. Herpes zoster, Kaposi's sarcoma and Pneumocystis carinii pneumonia were early manifestations, whereas...... diseases caused by cytomegalovirus and atypical mycobacteria tended to occur later in the course of AIDS. Compared with all other AIDS patients, homosexual men were more likely to develop Kaposi's sarcoma, cytomegalovirus chorioretinitis and mucocutaneous herpes simplex virus infection. The proportion...... of patients who developed particular diseases changed with calendar time. Most striking was a three to fourfold decrease in diseases caused by cytomegalovirus. In conclusion, the study showed that disease frequencies in patients with AIDS may vary with the patients risk behaviour and duration of AIDS...

  15. 29 CFR 500.231 - Appearances; representation of the Department of Labor.

    Science.gov (United States)

    2010-07-01

    ... OF LABOR REGULATIONS MIGRANT AND SEASONAL AGRICULTURAL WORKER PROTECTION Administrative Proceedings Procedures Before Administrative Law Judge § 500.231 Appearances; representation of the Department of...

  16. 231Pa/230Th records of Arctic/Atlantic interchange in Fram Strait

    Science.gov (United States)

    Hoffmann, S. S.; McDermott, K. J.; McManus, J. F.; Mukasa, S. B.

    2014-12-01

    Fram Strait, the Arctic Ocean's only deep passage for exchange with lower latitude oceans, today serves as a conduit for waters flowing north into the Arctic Ocean and south into the Atlantic. Reconstruction of circulation patterns and strength at depth in the strait can help to clarify the history of Arctic/Atlantic deep water exchange and Arctic contributions to global meridional overturning circulation. We will present new sedimentary measurements of radioisotopes 231Pa and 230Th to provide information on this exchange in the past and its relationship to sedimentation and climatic events. Coretop and downcore 231Pa/230Th ratios from Arctic sediments indicate that 231Pa has been exported from the central Arctic basin throughout the Holocene and deglaciation. Fram Strait represents a possible sink for this "missing" 231Pa. Preliminary results from ODP Holes 908A and 909A, at 1274 m and 2519 m water depths respectively in the central strait, suggest that ratios in this region during the Holocene have varied between ~0.106 (above the 231Pa/230Th production ratio of 0.093 in seawater, indicating net import of 231Pa)and ~0.055 (well below the production ratio, indicating net export of 231Pa). Further measurements in cores from the Greenland and Svalbard continental slopes will give a fuller regional picture of 231Pa deposition and transport across the strait.

  17. 22 CFR 231.05 - Non-impairment of the Guarantee.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Non-impairment of the Guarantee. 231.05 Section 231.05 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ARAB REPUBLIC OF EGYPT LOAN GUARANTEES... enforceability of any agreement or other document executed by a Noteholder, USAID, the Fiscal Agent or...

  18. The 2q23.1 microdeletion syndrome: clinical and behavioural phenotype.

    NARCIS (Netherlands)

    Bon, B.W.M. van; Koolen, D.A.; Brueton, L.; McMullan, D.; Lichtenbelt, K.D.; Ades, L.C.; Peters, G.; Gibson, K.; Moloney, S.; Novara, F.; Pramparo, T.; Bernardina, B. Dalla; Zoccante, L.; Balottin, U.; Piazza, F.; Pecile, V.; Gasparini, P.; Guerci, V.; Kets, M.; Pfundt, R.; Brouwer, A.P.M. de; Veltman, J.A.; Leeuw, N. de; Wilson, M.; Antony, J.; Reitano, S.; Luciano, D.; Fichera, M.; Romano, C.; Brunner, H.G.; Zuffardi, O.; Vries, L.B.A. de

    2010-01-01

    Six submicroscopic deletions comprising chromosome band 2q23.1 in patients with severe mental retardation (MR), short stature, microcephaly and epilepsy have been reported, suggesting that haploinsufficiency of one or more genes in the 2q23.1 region might be responsible for the common phenotypic

  19. The 2q23.1 microdeletion syndrome: clinical and behavioural phenotype.

    NARCIS (Netherlands)

    Bon, B.W.M. van; Koolen, D.A.; Brueton, L.; McMullan, D.; Lichtenbelt, K.D.; Ades, L.C.; Peters, G.; Gibson, K.; Moloney, S.; Novara, F.; Pramparo, T.; Bernardina, B. Dalla; Zoccante, L.; Balottin, U.; Piazza, F.; Pecile, V.; Gasparini, P.; Guerci, V.; Kets, M.; Pfundt, R.; Brouwer, A.P.M. de; Veltman, J.A.; Leeuw, N. de; Wilson, M.; Antony, J.; Reitano, S.; Luciano, D.; Fichera, M.; Romano, C.; Brunner, H.G.; Zuffardi, O.; Vries, L.B.A. de

    2010-01-01

    Six submicroscopic deletions comprising chromosome band 2q23.1 in patients with severe mental retardation (MR), short stature, microcephaly and epilepsy have been reported, suggesting that haploinsufficiency of one or more genes in the 2q23.1 region might be responsible for the common phenotypic fea

  20. EVN observations of the OH megamaser galaxies Mrk 231 and IC 694

    NARCIS (Netherlands)

    Klockner, HR; Baan, WA; Migenes,; Reid, MJ

    2002-01-01

    We present EVN observations of hydroxyl (OH) main-line emission in two megamaser sources Mrk 231 and IC 694. The observations indicate that the broad maser emission lines originate within the nuclear regions. A single 1667 MHz main-line feature is seen at the nucleus of IC 694. In Mrk 231 both

  1. 49 CFR 231.15 - Steam locomotives used in road service.

    Science.gov (United States)

    2010-10-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD SAFETY APPLIANCE STANDARDS § 231.15 Steam locomotives used... 49 Transportation 4 2010-10-01 2010-10-01 false Steam locomotives used in road service. 231.15... extends across front end of locomotive to within 8 inches of end of buffer-beam, and is seven-eighths...

  2. 48 CFR 231.205-18 - Independent research and development and bid and proposal costs.

    Science.gov (United States)

    2010-10-01

    ... and life-cycle costs of military systems. (3) Strengthen the defense industrial and technology base of... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Independent research and development and bid and proposal costs. 231.205-18 Section 231.205-18 Federal Acquisition Regulations System...

  3. 49 CFR 231.19 - Definition of “Right” and “Left.”

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Definition of âRightâ and âLeft.â 231.19 Section 231.19 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD...” and “Left.” Right or Left refers to side of person when facing end or side of car from ground....

  4. Herschel observations of water vapour in Markarian 231

    CERN Document Server

    González-Alfonso, E; Isaak, K; Rykala, A; Savini, G; Spaans, M; van der Werf, P; Meijerink, R; Israel, F P; Loenen, A F; Vlahakis, C; Smith, H A; Charmandaris, V; Aalto, S; Henkel, C; Weiß, A; Walter, F; Greve, T R; Martín-Pintado, J; Naylor, D A; Spinoglio, L; Veilleux, S; Harris, A I; Armus, L; Lord, S; Mazzarella, J; Xilouris, E M; Sanders, D B; Dasyra, K M; Wiedner, M C; Kramer, C; Papadopoulos, P P; Stacey, G J; Evans, A S; Gao, Y

    2010-01-01

    The Ultra Luminous InfraRed Galaxy Mrk 231 reveals up to seven rotational lines of water (H2O) in emission, including a very high-lying (E_{upper}=640 K) line detected at a 4sigma level, within the Herschel/SPIRE wavelength range, whereas PACS observations show one H2O line at 78 microns in absorption, as found for other H2O lines previously detected by ISO. The absorption/emission dichotomy is caused by the pumping of the rotational levels by far-infrared radiation emitted by dust, and subsequent relaxation through lines at longer wavelengths, which allows us to estimate both the column density of H2O and the general characteristics of the underlying far-infrared continuum source. Radiative transfer models including excitation through both absorption of far-infrared radiation emitted by dust and collisions are used to calculate the equilibrium level populations of H2O and the corresponding line fluxes. The highest-lying H2O lines detected in emission, with levels at 300-640 K above the ground state, indicate...

  5. A mir-231-Regulated Protection Mechanism against the Toxicity of Graphene Oxide in Nematode Caenorhabditis elegans

    Science.gov (United States)

    Yang, Ruilong; Ren, Mingxia; Rui, Qi; Wang, Dayong

    2016-08-01

    Recently, several dysregulated microRNAs (miRNAs) have been identified in organisms exposed to graphene oxide (GO). However, their biological functions and mechanisms of the action are still largely unknown. Here, we investigated the molecular mechanism of mir-231 in the regulation of GO toxicity using in vivo assay system of Caenorhabditis elegans. We found that GO exposure inhibited the expression of mir-231::GFP in multiple tissues, in particular in the intestine. mir-231 acted in intestine to regulate the GO toxicity, and overexpression of mir-231 in intestine caused a susceptible property of nematodes to GO toxicity. smk-1 encoding a homologue to mammalian SMEK functioned as a targeted gene for mir-231, and was also involved in the intestinal regulation of GO toxicity. Mutation of smk-1 gene induced a susceptible property to GO toxicity, whereas the intestinal overexpression of smk-1 resulted in a resistant property to GO toxicity. Moreover, mutation of smk-1 gene suppressed the resistant property of mir-231 mutant to GO toxicity. In nematodes, SMK-1 further acted upstream of the transcriptional factor DAF-16/FOXO in insulin signaling pathway to regulate GO toxicity. Therefore, mir-231 may encode a GO-responsive protection mechanism against the GO toxicity by suppressing the function of the SMK-1 - DAF-16 signaling cascade in nematodes.

  6. In vitro mutagen binding and antimutagenic activity of human Lactobacillus rhamnosus 231.

    Science.gov (United States)

    Ambalam, Padma; Dave, J M; Nair, Baboo M; Vyas, B R M

    2011-10-01

    In vitro mutagen binding ability of human Lactobacillus rhamnosus 231 (Lr 231) was evaluated against acridine orange (AO), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), 2-amino-3, 8-dimethylimidazo-[4,5-f]-quinoxaline (MeIQx) and 4-nitro-o-phenylenediamine (NPD). Binding of AO by Lr 231 is due to adsorption, thereby leading to removal of mutagen in solution and is instantaneous, pH- and concentration-dependent. Whereas, binding of MNNG and MeIQx by Lr 231 results into biotransformation leading to detoxification with subsequent loss of mutagenicity as determined by spectral analysis, thin layer chromatography and Ames test. Binding of mutagen by Lr 231 was dependent on culture age and optimum binding of AO, MNNG and MeIQx was observed to occur with 24 h old culture. Cells of Lr 231 were subjected to different chemical treatments prior to binding studies. Results indicated cell wall component such as cell wall polysaccharide, peptidoglycan, carbohydrates and proteins plays an important role in adsorption of AO, also involving hydrophilic and ionic interactions. Binding, biotransformation and detoxification of MNNG and MeIQx by Lr 231 was dependent on cell surface characteristics mainly involving carbohydrates, proteins, teichoic acid/lipoteichoic acid, hydrophobic interaction and presence of thiol group. L. rhamnosus 231 bound MNNG instantaneously. More than 96 (p mutagen binding and various pretreatments respectively. This study shows Lr 231 exhibits ability to bind and detoxify potent mutagens, and this property can be useful in formulating fermented foods for removal of potent mutagens.

  7. 49 CFR 231.1 - Box and other house cars built or placed in service before October 1, 1966.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Box and other house cars built or placed in... APPLIANCE STANDARDS § 231.1 Box and other house cars built or placed in service before October 1, 1966. Except for box and other house cars that comply with either § 231.27 or § 231.28, each box and...

  8. 8 CFR 231.2 - Electronic manifest and I-94 requirement for passengers and crew onboard departing vessels and...

    Science.gov (United States)

    2010-01-01

    ... section 231 of the Act are set forth in 19 CFR 4.64 (passengers and crew members onboard vessels) and in 19 CFR 122.75a (passengers onboard aircraft) and 122.75b (crew members onboard aircraft). (b... for passengers and crew onboard departing vessels and aircraft. 231.2 Section 231.2 Aliens...

  9. 8 CFR 231.1 - Electronic manifest and I-94 requirement for passengers and crew onboard arriving vessels and...

    Science.gov (United States)

    2010-01-01

    ... section 231 of the Act are set forth in 19 CFR 4.7b (passengers and crew members onboard vessels) and in 19 CFR 122.49a (passengers onboard aircraft) and 122.49b (crew members onboard aircraft). (b... for passengers and crew onboard arriving vessels and aircraft. 231.1 Section 231.1 Aliens...

  10. 32 CFR Appendix C to Part 231 - Sample Certificate of Compliance for Credit Unions Certificate of Compliance

    Science.gov (United States)

    2010-07-01

    ... Unions Certificate of Compliance C Appendix C to Part 231 National Defense Department of Defense... UNIONS AND OTHER FINANCIAL INSTITUTIONS ON DOD INSTALLATIONS Pt. 231, App. C Appendix C to Part 231... union complies with the requirements of section 170 of the Federal Credit Union Act (12 U.S.C 1770),...

  11. File list: InP.Brs.50.AllAg.MDA-MB-231 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Brs.50.AllAg.MDA-MB-231 hg19 Input control Breast MDA-MB-231 SRX883581,SRX88358...46863,SRX1156474,SRX737089 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Brs.50.AllAg.MDA-MB-231.bed ...

  12. File list: NoD.Brs.10.AllAg.MDA-MB-231 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Brs.10.AllAg.MDA-MB-231 hg19 No description Breast MDA-MB-231 ERX309839,ERX3098...45 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/NoD.Brs.10.AllAg.MDA-MB-231.bed ...

  13. File list: NoD.Brs.05.AllAg.MDA-MB-231 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Brs.05.AllAg.MDA-MB-231 hg19 No description Breast MDA-MB-231 ERX309839,ERX3098...45 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/NoD.Brs.05.AllAg.MDA-MB-231.bed ...

  14. File list: InP.Brs.05.AllAg.MDA-MB-231 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Brs.05.AllAg.MDA-MB-231 hg19 Input control Breast MDA-MB-231 SRX883581,SRX88358...56474,SRX332680,SRX1156475 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Brs.05.AllAg.MDA-MB-231.bed ...

  15. File list: NoD.Brs.50.AllAg.MDA-MB-231 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Brs.50.AllAg.MDA-MB-231 hg19 No description Breast MDA-MB-231 ERX309839,ERX3098...45 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/NoD.Brs.50.AllAg.MDA-MB-231.bed ...

  16. File list: InP.Brs.10.AllAg.MDA-MB-231 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Brs.10.AllAg.MDA-MB-231 hg19 Input control Breast MDA-MB-231 SRX883581,SRX88358...56474,SRX246863,SRX1156475 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Brs.10.AllAg.MDA-MB-231.bed ...

  17. File list: InP.Brs.20.AllAg.MDA-MB-231 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Brs.20.AllAg.MDA-MB-231 hg19 Input control Breast MDA-MB-231 SRX883581,SRX88358...156475,SRX332680,SRX246863 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Brs.20.AllAg.MDA-MB-231.bed ...

  18. 75 FR 30902 - Supplemental Draft Environmental Impact Statement; U.S. 231 Dubois County, IN

    Science.gov (United States)

    2010-06-02

    ... route, U.S. 231 is included in the National Highway System (NHS). The NHS includes all Interstate routes... national defense. The NHS includes 5 percent of the national roadway network but serves approximately...

  19. Involvement of TBL/DUF231 proteins into cell wall biology

    OpenAIRE

    Bischoff, Volker; Selbig, Joachim; Scheible, Wolf-Rüdiger

    2010-01-01

    Through map-based cloning we determined TRICHOME BIREFRINGENCE (TBR) belongs to a plant-specific, yet anonymous gene family with 46 members in Arabidopsis thaliana. These genes all encode the domain of unknown function 231 (DUF231). TBR and its homolog TRICHOME BIREFRINGENCE-LIKE3 (TBL3) are transcriptionally coordinated with CELLULOSE SYNTHASE (CESA) genes, and loss of TBR or TBL3 results in decreased levels of crystalline secondary wall cellulose in trichomes and stems, respectively. Loss o...

  20. Action and Signaling of Lysophosphatidylethanolamine in MDA-MB-231 Breast Cancer Cells.

    Science.gov (United States)

    Park, Soo-Jin; Lee, Kyoung-Pil; Im, Dong-Soon

    2014-02-01

    Previously, we reported that lysophosphatidylethanolamine (LPE), a lyso-type metabolite of phosphatidylethanolamine, can increase intracellular Ca(2+) ([Ca(2+)]i) via type 1 lysophosphatidic acid (LPA) receptor (LPA1) and CD97, an adhesion G-protein-coupled receptor (GPCR), in MDA-MB-231 breast cancer cells. Furthermore, LPE signaling was suggested as like LPA1/CD97-Gi/o proteins-phospholipase C-IP3-Ca(2+) increase in these cells. In the present study, we further investigated actions of LPE not only in the [Ca(2+)]i increasing effect but also in cell proliferation and migration in MDA-MB-231 breast cancer cells. We utilized chemically different LPEs and a specific inhibitor of LPA1, AM-095 in comparison with responses in SK-OV3 ovarian cancer cells. It was found that LPE-induced Ca(2+) response in MDA-MB-231 cells was evoked in a different manner to that in SK-OV3 cells in terms of structural requirements. AM-095 inhibited LPE-induced Ca(2+) response and cell proliferation in MDA-MB-231 cells, but not in SK-OV3 cells, supporting LPA1 involvement only in MDA-MB-231 cells. LPA had significant effects on cell proliferation and migration in MDA-MB-231 cells, whereas LPE had less or no significant effect. However, LPE modulations of MAPKs (ERK1/2, JNK and p38 MAPK) was not different to those by LPA in the cells. These data support the involvement of LPA1 in LPE-induced Ca(2+) response and cell proliferation in breast MDA-MB-231 cells but unknown GPCRs (not LPA1) in LPE-induced responses in SK-OV3 cells. Furthermore, although LPE and LPA utilized LPA1, LPA utilized more signaling cascades than LPE, resulting in stronger responses by LPA in proliferation and migration than LPE in MDA-MB-231 cells.

  1. [Effect of Aloe emodin on invasion and metastasis of high metastatic breast cancer MDA-MB-231 cells].

    Science.gov (United States)

    He, Zhen-Hui; Huang, Yue-Qun; Weng, Shan-Fan; Tan, Yao-Rong; He, Tai-Ping; Qin, Yan-Mei; Liang, Nian-Ci

    2013-09-01

    To investigate the effect of Aloe emodin (AE) on the invasive and metastatic abilities of human high metastatic breast cancer MDA-MB-231 cells. MTT assay was used to evaluate the viability of MDA-MB-231 cells after treated with AE for 6 h and 24 h. The adhesive potential of MDA-MB-231 cells to FN and LN was tested by cell-matrix adhesion assay. The effect of AE on invasion of MDA-MB-231 cells was measured by Transwell chamber assay. Scratch wound healing assay was applied to determine the effect on migration of MDA-MB-231 cells. The effect of AE on MDA-MB-231 lung metastasis was determined on an experimental metastatic model. 80 micromol/L AE significantly inhibited the invasion, adhesion to FN, LN of MDA-MB-231 cells in vitro, the inhibitory rates were (52.98 +/- 5.46)%, (34.99 +/- 2.63)%, (28.73 +/- 7.00)%, respectively. After 24 h treatment, AE significantly inhibited the migration of MDA-MB-231 cells. The number and volume of lung metastatic nodules formed by MDA-MB-231 cells after 80 micromol/L AE 24 h treatment were decreased compared with control group. AE can suppress the metastasis of MDA-MB-231 cells. Their mechanisms may be related to the inhibition of the capabilities of invasion and migration of MDA-MB-231 cells.

  2. Characterization of past and present solid waste streams from 231-Z

    Energy Technology Data Exchange (ETDEWEB)

    Pottmeyer, J.A.; DeLorenzo, D.S.; Weyns-Rollosson, M.I.; Berkwitz, D.E.; Vejvoda, E.J. [Los Alamos Technical Associates, Inc., NM (US); Duncan, D.R. [Westinghouse Hanford Co., Richland, WA (US)

    1993-06-01

    During the next two decades the transuranic (TRU) wastes now stored in the burial trenches and storage facilities at the Hanford Site are to be retrieved, processed at the Waste Receiving and Processing Facility, and shipped to the Waste Isolation Pilot Plant near Carlsbad, New Mexico for final disposal. Over 8% of the TRU waste to be retrieved for shipment to the Waste Isolation Pilot Plant has been generated at the Plutonium Metallurgy Laboratory (231-Z) Facility. The purpose of this report is to characterize the radioactive solid wastes generated by 231-Z using process knowledge, existing records and oral history interviews. Since 1944 research and development programs utilizing plutonium have been conducted at 231-Z in the fields of physical metallurgy, property determination, alloy development, and process development. The following are sources of solid waste generation at the 231-Z Facility: (1) General Weapons Development Program, (2) process waste from gloveboxes, (3) numerous classified research and development programs, (4) advanced decontamination and decommissioning technologies, including sectioning, vibratory finishing, electropolishing, solution process, and small bench-scale work, (5) general laboratory procedures, (6) foundry area, (7) housekeeping activities, and (8) four cleanout campaigns. All solid wastes originating at 231-Z were packaged for onsite-offsite storage or disposal. Waste packaging and reporting requirements have undergone significant changes throughout the history of 231-Z. Current and historical procedures are provided in Section 4.0. Information on the radioactive wastes generated at 231-Z can be found in a number of documents and databases, most importantly the Solid Waste Information and Tracking System database and Solid Waste Burial Records. Facility personnel also provide excellent information about past waste generation and the procedures used to handle that waste. Section 5.0 was compiled using these sources.

  3. Hypoxia regulates stemness of breast cancer MDA-MB-231 cells.

    Science.gov (United States)

    Xie, Jing; Xiao, Yong; Zhu, Xiao-yan; Ning, Zhou-yu; Xu, Hai-fan; Wu, Hui-min

    2016-05-01

    Human breast cancers include cancer stem cell populations as well as non-tumorigenic cancer cells. Breast cancer stem cells possess self-renewal capability and thus are the root cause of recurrence and metastasis of malignant tumors. Hypoxia is a fundamental pathological feature of solid tumor tissues and exerts a wide range of effects on the biological behavior of cancer cells. However, there is little information on the role of hypoxia in modulating the stemness of breast cancer cells. In the present study, we cultured MDA-MB-231 cells in a hypoxic gas mixture to simulate the hypoxic environment in tissues and to determine how hypoxia conditions could affect the cell proliferation, apoptosis, cytotoxicity, and colony-forming ability. Expression of the stem cell phenotype CD24(-)CD44(+)ESA(+) was analyzed to assess the effects of hypoxia on stemness transformation in MDA-MB-231 cells. Our results found that the cell toxicity of MDA-MB-231 cells was not affected by hypoxia. Hypoxia could slightly inhibit the growth of MDA-MB-231 cells, but the inhibitory effect is not significant when compared with normoxic control. Moreover, hypoxia significantly blocked the apoptosis in MDA-MB-231 cells (P MB-231 cells was increased greatly after they were treated with hypoxia, and cell colony-formation rate of MDA-MB-231 cells also increased significantly in hypoxia-treated cells. These results encourage the exploration of hypoxia as a mechanism which might not be underestimated in chemo-resistant breast cancer treatment.

  4. Effect of amlodipine on apoptosis of human breast carcinoma MDA-MB-231 cells

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Objective: To elucidate the effects of amlodipine on the proliferation and apoptosis of human breast carcinoma MDA-MB-231 cells. Methods: Light microscopy was used to determine the effects of amiodipine on cell morphology; Flow cytometry was used to quantitate cells undergoing apoptosis; the expression of a cell cycle-related protein, proliferating cell nuclear antigen (PCNA) and an antiapoptosis protein, Bcl-2 were assessed by immunocytochemistry. Results: Amlodipine concentration of 8.25 Ixmol/L (1/2 of IC50) affected the morphology, decreased the expression of PCNA and Bcl-2 and induced apoptosis of human breast carcinoma MDA-MB-231 cells. Conclusion: The effect of amlodipine on the antiproliferation of human breast carcinoma MDA-MB-231 cells is related to inducement of apoptosis, and the decrease of the expression of Bcl-2 and PCNA may be the possible mechanism for proliferation inhibitory and inducement of apoptosis.

  5. Protein Profiles Associated with Anoikis Resistance of Metastatic MDA-MB-231 Breast Cancer Cells.

    Science.gov (United States)

    Akekawatchai, Chareeporn; Roytrakul, Sittiruk; Kittisenachai, Suthathip; Isarankura-Na-Ayudhya, Patcharee; Jitrapakdee, Sarawut

    2016-01-01

    Resistance to anoikis, a cell-detachment induced apoptosis, is one of the malignant phenotypes which support tumor metastasis. Molecular mechanisms underlying the establishment of this phenotype require further investigation. This study aimed at exploring protein expression profiles associated with anoikis resistance of a metastatic breast cancer cell. Cell survival of suspension cultures of non-metastatic MCF-7 and metastatic MDA-MB-231 cells were compared with their adherent cultures. Trypan blue exclusion assays demonstrated a significantly higher percentage of viable cells in MDA-MB-231 than MCF-7 cell cultures, consistent with analysis of annexin V-7-AAD stained cells indicating that MDA-MB-231 possess anti-apoptotic ability 1.7 fold higher than MCF-7 cells. GeLC-MS/MS analysis of protein lysates of MDA-MB-231 and MCF-7 cells grown under both culture conditions identified 925 proteins which are differentially expressed, 54 of which were expressed only in suspended and adherent MDA-MB-231 but not in MCF-7 cells. These proteins have been implicated in various cellular processes, including DNA replication and repair, transcription, translation, protein modification, cytoskeleton, transport and cell signaling. Analysis based on the STITCH database predicted the interaction of phospholipases, PLC and PLD, and 14-3-3 beta/alpha, YWHAB, with the intrinsic and extrinsic apoptotic signaling network, suggesting putative roles in controlling anti-anoikis ability. MDA-MB-231 cells grown in the presence of inhibitors of phospholipase C, U73122, and phospholipase D, FIPI, demonstrated reduced ability to survive in suspension culture, indicating functional roles of PLC and PLD in the process of anti-anoikis. Our study identified intracellular mediators potentially associated with establishment of anoikis resistance of metastatic cells. These proteins require further clarification as prognostic and therapeutic targets for advanced breast cancer.

  6. Acute severe head injury resulted from road traffic accidents:a report on 231 cases

    Institute of Scientific and Technical Information of China (English)

    刘敬业; 张赛; 等

    1999-01-01

    Objective:To analyze the epidemiology and clinical outcome of acute severe head injurey induced by road traffic accidents.Methods:The data of 231 patients with acute severe head injury induced by road traffic accidents were retrospectively studied.Results:The major victim-maker was automobiles (98.8%).The first three common types of traffic accidents were automobiles crashing into automobiles,automobiles crashing into bicycles(42.9%),and automobiles crashing pedestrians(40.3%).Eighty-seven patients out of 231 died,with the mortality of 37.7%.Conclusions:It suggests tat improving traffic administration and traffic safety consciousness may significantly reduce traffic trauma.

  7. Conserved aspartic acid 233 and alanine 231 are not required for poliovirus polymerase function in replicons

    Directory of Open Access Journals (Sweden)

    Freistadt Marion S

    2007-03-01

    Full Text Available Abstract Nucleic acid polymerases have similar structures and motifs. The function of an aspartic acid (conserved in all classes of nucleic acid polymerases in motif A remains poorly understood in RNA-dependent RNA polymerases. We mutated this residue to alanine in a poliovirus replicon. The resulting mutant could still replicate, although at a reduced level. In addition, mutation A231C (also in motif A yielded high levels of replication. Taken together these results show that poliovirus polymerase conserved residues D233 and A231 are not essential to poliovirus replicon function.

  8. Conserved aspartic acid 233 and alanine 231 are not required for poliovirus polymerase function in replicons

    Science.gov (United States)

    Freistadt, Marion S; Eberle, Karen E

    2007-01-01

    Nucleic acid polymerases have similar structures and motifs. The function of an aspartic acid (conserved in all classes of nucleic acid polymerases) in motif A remains poorly understood in RNA-dependent RNA polymerases. We mutated this residue to alanine in a poliovirus replicon. The resulting mutant could still replicate, although at a reduced level. In addition, mutation A231C (also in motif A) yielded high levels of replication. Taken together these results show that poliovirus polymerase conserved residues D233 and A231 are not essential to poliovirus replicon function. PMID:17352827

  9. Infrared spectrophotometry of OH 231.8 + 4.2 identified with OH 0739-14

    Science.gov (United States)

    Gillett, F. C.; Soifer, B. T.

    1976-01-01

    Infrared spectrophotometry from 2.1 to 4.1 microns and from 7.7 to 13.3 microns of the peculiar OH maser source OH 231.8 + 4.2 identified with OH 0739-14 is reported. Deep absorption features are found at 3.1 microns and from 8 to 13 microns, and are identified with absorption by cold ices and silicates in the line of sight to the infrared source. The infrared flux is also found to vary. These infrared observations present new difficulties in understanding the nature of the object. Several possibly useful observations of OH 231.8 + 4.2 are suggested.

  10. 9 CFR 2.31 - Institutional Animal Care and Use Committee (IACUC).

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Institutional Animal Care and Use..., DEPARTMENT OF AGRICULTURE ANIMAL WELFARE REGULATIONS Research Facilities § 2.31 Institutional Animal Care and... Institutional Animal Care and Use Committee (IACUC), qualified through the experience and expertise of...

  11. 7 CFR 1280.231 - Patents, copyrights, inventions, product formulations, and publications.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Patents, copyrights, inventions, product formulations... Information Order Miscellaneous § 1280.231 Patents, copyrights, inventions, product formulations, and publications. (a) Any patents, copyrights, inventions or publications developed through the use of...

  12. Draft Genome Sequence of Propane- and Butane-Oxidizing Actinobacterium Rhodococcus ruber IEGM 231

    OpenAIRE

    Ivshina, Irena B.; Kuyukina, Maria S.; Krivoruchko, Anastasiya V.; Barbe, Valérie; Fischer, Cécile

    2014-01-01

    We report a draft genome sequence of Rhodococcus ruber IEGM 231, isolated from a water spring near an oil-extracting enterprise (Perm region, Russian Federation). This sequence provides important insights into the genetic mechanisms of propane and n-butane metabolism, organic sulfide and beta-sitosterol biotransformation, glycolipid biosurfactant production, and heavy metal resistance in actinobacteria.

  13. Draft Genome Sequence of Propane- and Butane-Oxidizing Actinobacterium Rhodococcus ruber IEGM 231.

    Science.gov (United States)

    Ivshina, Irena B; Kuyukina, Maria S; Krivoruchko, Anastasiya V; Barbe, Valérie; Fischer, Cécile

    2014-12-11

    We report a draft genome sequence of Rhodococcus ruber IEGM 231, isolated from a water spring near an oil-extracting enterprise (Perm region, Russian Federation). This sequence provides important insights into the genetic mechanisms of propane and n-butane metabolism, organic sulfide and beta-sitosterol biotransformation, glycolipid biosurfactant production, and heavy metal resistance in actinobacteria.

  14. 24 CFR 248.231 - Incentives to extend low income use.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Incentives to extend low income use... AUTHORITIES PREPAYMENT OF LOW INCOME HOUSING MORTGAGES Prepayment and Plans of Action Under the Emergency Low Income Preservation Act of 1987 § 248.231 Incentives to extend low income use. The Commissioner may...

  15. 48 CFR 231.205-1 - Public relations and advertising costs.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Public relations and... PROCEDURES Contracts With Commercial Organizations 231.205-1 Public relations and advertising costs. (e) See... public relations and advertising costs also include monies paid to the Government associated with...

  16. Involvement of TBL/DUF231 proteins into cell wall biology.

    Science.gov (United States)

    Bischoff, Volker; Selbig, Joachim; Scheible, Wolf-Rüdiger

    2010-08-01

    Through map-based cloning we determined TRICHOME BIREFRINGENCE (TBR) to belong to a plant-specific, yet anonymous gene family with 46 members in Arabidopsis thaliana. These genes all encode the domain of unknown function 231 (DUF231). TBR and its homolog TRICHOME BIREFRINGENCE-LIKE3 (TBL3) are transcriptionally coordinated with CELLULOSE SYNTHASE (CESA) genes, and loss of TBR or TBL3 results in decreased levels of crystalline secondary wall cellulose in trichomes and stems, respectively. Loss of TBR or TBL3 further results in increased pectin methylesterase (PME) activity and reduced pectin esterification in etiolated Arabidopsis hypocotyls. Together, the results suggest that DUF231 proteins might function in the maintenance of pectin- and probably homogalacturonan esterification, and that this is a requirement for normal secondary wall cellulose synthesis, at least in some tissues and organs. Here we expand the discussion about the role of TBL/DUF231 proteins in cell wall biology based on sequence and structure analyses. Our analysis revealed structural similarities of TBR with a rhamnogalacturonan acetylesterase (RGAE) of Aspergillus aculeatus and the protein LUSTRIN A-LIKE (Oryza sativa). The implications of these findings in regard to TBL functions are discussed.

  17. 49 CFR 231.17 - Specifications common to all steam locomotives.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Specifications common to all steam locomotives... RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD SAFETY APPLIANCE STANDARDS § 231.17 Specifications common to all steam locomotives. (a) Hand brakes. (1) Hand brakes will not be required...

  18. Search for class II methanol masers at 23.1 GHz

    CERN Document Server

    Cragg, D M; Caswell, J L; Ellingsen, S P; Godfrey, P D

    2004-01-01

    In the early days of methanol maser discoveries the 9(2)-10(1) A+ transition at 23.1 GHz was found to exhibit maser characteristics in the northern star-forming region W3(OH), and probable maser emission in two other sources. Attention subsequently turned to the 6.6-GHz 5(1)-6(0) A+ methanol maser transition, which has proved a valuable tracer of early high-mass star formation. We have undertaken a new search for 23.1-GHz methanol masers in 50 southern star formation regions using the Parkes radiotelescope. The target sources all exhibit class II methanol maser emission at 6.6 GHz, with 20 sources also displaying maser features in the 107.0-GHz 3(1)-4(0) A+ methanol line. Strong emission at 23.1 GHz in NGC 6334F was confirmed, but no emission was detected in the remaining sources. Thus the 23.1-GHz methanol masers are rare. A maser model in which methanol molecules are pumped to the second torsionally excited state by radiation from warm dust can account for class II maser activity in all the transitions in w...

  19. Engagement of membrane immunoglobulin enhances Id3 promoter activity in WEHI-231 B lymphoma cells

    Institute of Scientific and Technical Information of China (English)

    Xiao-jun LI; Kikumi HATA; Junichiro MIZUGUCHI

    2005-01-01

    Aim: We have recently shown that engagement of membrane immunoglobulin (mIg) induced upregulation of inhibitor of differentiation 3 (Id3) mRNA, resulting in growth arrest at G1 phase in WEHI-231 cells. In the present study, we examined whether engagement of mIg will affect promoter activity of the Id3 gene in WEHI231 cells. Methods: DNA fragments corresponding to the 5′-flanking region of mId3 gene were amplified by polymerase chain reaction (PCR) using genomic DNA as the template. Three DNA fragments upstream of the transcription start site (+ 1) of the mId3 gene were subcloned into the luciferase reporter vector PGVB2. The recombinant constructs were transiently transfected into WEHI-231 cells by an electroporation method. After incubation for 24 h, WEHI-231 cells were stimulated with 10 mg/L anti-IgM or irradiated CD40L-expressing NIH3T3 cells or control NIH3T3 cells for further 24 h, followed by assay for luciferase activity. Results: The luciferase analysis demonstrated that basal promoter activity of the Id3 gene was found in the region between -200 and +54. The Id3 promoter activity was increased 2-fold following stimulation with anti-IgM, but not CD40L, compared with medium alone. Conclusion: The mIg-mediated upregulation of Id3 expression is controlled, at least in part, through transcriptional regulation, as assessed by luciferase assay.

  20. X-231B technology demonstration for in situ treatment of contaminated soil: Technology evaluation and screening

    Energy Technology Data Exchange (ETDEWEB)

    Siegrist, R.L.; Morris, M.I.; Donaldson, T.L.; Palumbo, A.V.; Herbes, S.E.; Jenkins, R.A.; Morrissey, C.M.; Harris, M.T.

    1993-08-01

    The Portsmouth Gaseous Diffusion Plant (Ports) is located approximately 70 miles south of Columbus in southern Ohio. Among the several waste management units on the facility, the X-231B unit consists of two adjacent oil biodegradation plots. The plots encompass {approximately} 0.8 acres and were reportedly used from 1976 to 1983 for the treatment and disposal of waste oils and degreasing solvents, some containing uranium-235 and technetium-99. The X-231B unit is a regulated solid waste management unit (SWMU) under the Resource Conservation and Recovery Act (RCRA). The X-231B unit is also a designated SWMU located within Quadrant I of the site as defined in an ongoing RCRA Facilities Investigation and Corrective Measures Study (RFI/CMS). Before implementing one or more Technology Demonstration Project must be completed. The principal goal of this project was to elect and successfully demonstrate one ore more technologies for effective treatment of the contaminated soils associated with the X-231B unit at PORTS. The project was divided into two major phases. Phase 1 involved a technology evaluation and screening process. The second phase (i.e., Phase 2) was to involve field demonstration, testing and evaluation of the technology(s) selected during Phase 1. This report presents the methods, results, and conclusions of the technology evaluation and screening portion of the project.

  1. 28 CFR 2.31 - Parole to detainers: Statement of policy.

    Science.gov (United States)

    2010-07-01

    ... RECOMMITMENT OF PRISONERS, YOUTH OFFENDERS, AND JUVENILE DELINQUENTS United States Code Prisoners and Parolees § 2.31 Parole to detainers: Statement of policy. (a) Where a detainer is lodged against a prisoner, the Commission may grant parole if the prisoner in other respects meets the criteria set forth in § 2...

  2. 5 CFR 591.231 - Which areas are post differential areas?

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Which areas are post differential areas... REGULATIONS ALLOWANCES AND DIFFERENTIALS Cost-of-Living Allowance and Post Differential-Nonforeign Areas Post Differentials § 591.231 Which areas are post differential areas? OPM has established the following...

  3. 230Thand 231Pa in Seawater Sinking Particles from the North Atlantic GEOTRACES Transect

    Science.gov (United States)

    LU, Y.; Edwards, R. L.; Cheng, H.; Anderson, R. F.; Hayes, C. T.; Fleisher, M. Q.; Lam, P. J.; Huang, K. F.; Robinson, L. F.; Wang, X.

    2016-12-01

    The biological carbon pump in the ocean plays a key role in regulating atmospheric CO2 level via oceanic particle dynamics. Radionuclides with proper half-lives, like 230Th and 231Pa, can provide quantitative estimates of particle cycling on the timescales up to hundred thousand years. However, our understanding of particle dynamics is hindered by the difficulty in precisely determining particulate 230Th and 231Pa, due to the trace amounts of Th and Pa in seawater, especially in large sinking particles. Here, we developed a technique to measure sinking particulate 230Th and 231Pa in a small sample size (tens to hundreds attograms of 231Pa, equivalent to 100 L water pumped through QMA filter), and achieved an average precision in percentage level. We firstly applied leaching processes to the particulate samples. The samples were soaked in 8N HNO3 + 0.5N HF mixed with proportionally determined 229Th and 233Pa spikes, and heated at 100°C for 10 hours. Th and Pa were then pre-concentrated by co-precipitation with Fe. After HNO3-HClO4-HNO3 digestion of the precipitates, Th and Pa were separated and purified using anion exchange chromatography (Spectra/Gel anion resin 1x8). Pa was measured on a MC-ICP-MS instrument (Neptune) right after the chemistry in order to minimize the 233Pa "bleeding effect". Replication tests show a good agreement in 231Pa/230Th within the measurement uncertainties. Applying our method to the profile samples collected from the North Atlantic GEOTRACES Transect, we found that the concentrations of 230Th and 231Pa in sinking particles (>51 μm size fraction; attograms/liter) are about 1/10 of those in suspended ones (1 - 51 μm size fraction). The scavenging of Th and Pa to large particles appears to be a function of particle composition (CaCO3, POM, lithogenic, opal and Fe/Mn oxides). In addition, ratios of the adsorbed 231Pa to 230Th are the same in both types of particles, although the particles have significantly different residence time in

  4. Calhex231 Ameliorates Cardiac Hypertrophy by Inhibiting Cellular Autophagy in Vivo and in Vitro

    Directory of Open Access Journals (Sweden)

    Lei Liu

    2015-07-01

    Full Text Available Background/Aims: Intracellular calcium concentration ([Ca2+]i homeostasis, an initial factor of cardiac hypertrophy, is regulated by the calcium-sensing receptor (CaSR and is associated with the formation of autolysosomes. The aim of this study was to investigate the role of Calhex231, a CaSR inhibitor, on the hypertrophic response via autophagy modulation. Methods: Cardiac hypertrophy was induced by transverse aortic constriction (TAC in 40 male Wistar rats, while 10 rats underwent a sham operation and served as controls. Cardiac function was monitored by transthoracic echocardiography, and the hypertrophy index was calculated. Cardiac tissue was stained with hematoxylin and eosin (H&E or Masson's trichrome reagent and examined by transmission electron microscopy. An angiotensin II (Ang II-induced cardiomyocyte hypertrophy model was established and used to test the involvement of active molecules. Intracellular calcium concentration ([Ca2+]i was determined by the introduction of Fluo-4/AM dye followed by confocal microscopy. The expression of various active proteins was analyzed by western blot. Results: The rats with TAC-induced hypertrophy had an increased heart size, ratio of heart weight to body weight, myocardial fibrosis, and CaSR and autophagy levels, which were suppressed by Calhex231. Experimental results using Ang II-induced hypertrophic cardiomyocytes confirmed that Calhex231 suppressed CaSR expression and downregulated autophagy by inhibiting the Ca2+/calmodulin-dependent-protein kinase-kinase-β (CaMKKβ- AMP-activated protein kinase (AMPK-mammalian target of rapamycin (mTOR pathway to ameliorate cardiomyocyte hypertrophy. Conclusions: Calhex231 ameliorates myocardial hypertrophy induced by pressure-overload or Ang II via inhibiting CaSR expression and autophagy. Our results may support the notion that Calhex231 can become a new therapeutic agent for the treatment of cardiac hypertrophy.

  5. Congenital diaphragmatic hernia interval on chromosome 8p23.1 characterized by genetics and protein interaction networks

    DEFF Research Database (Denmark)

    Longoni, Mauro; Hansen, Kasper Lage; Russell, Meaghan K.

    2012-01-01

    Chromosome 8p23.1 is a common hotspot associated with major congenital malformations, including congenital diaphragmatic hernia (CDH) and cardiac defects. We present findings from high‐resolution arrays in patients who carry a loss (n = 18) or a gain (n = 1) of sub‐band 8p23.1. We confirm a regio...

  6. The effect of baicalein on the expression of SATB1 in MDA-MB-231 cells

    Institute of Scientific and Technical Information of China (English)

    Xiaoyan Gao; Xingcong Ma; Yinan Ma; Xinghuan Xue; Shuqun Zhang

    2014-01-01

    Objective:Baicalein had been proved to have anti-cancer activity in vitro and in vivo, including the inhibition of malignant proliferation, migration, adhesion and invasion of many kinds of cancer cel s. The special AT-rich sequence binding protein 1 (SATB1) is a tissue-specific expression of nuclear matrix-binding protein and is reported to be a breast cancer“gene group organizer”. Previous studies have shown that SATB1 is involved in the growth, metastasis and prognosis of breast cancer. The present study was aimed to investigate whether baicalein inhibits the proliferation and migration of MDA-MB-231 human breast cancer cel s through down-regulation of the SATB1 expression. Methods:MDA-MB-231 cel s were treated for 24 h, 48 h and 72 h with various concentrations of baicalein (0, 5, 10, 20, 40 and 80μM) respectively. Then, the proliferation and migration of MDA-MB-231 cel s fol owing treatment with baicalein were determined using colorimetric 3-(4, 5-dimethylthia-zol-2-yl) 2, 5-diphenyltetrazolium bromide (MTT) and wound healing assays. Thereafter, western blot analysis was performed to detect the changes of SATB1 protein expression in MDA-MB-231 cel s. Results:Along with the prolongation of time and increase of drug concentration, inhibitory ef ect of baicalein on proliferation and migration of MDA-MB-231 cel s gradual y in-creased, in a time-and dose-dependent manner (P<0.05). Meanwhile, after treated with baicalein in dif erent concentrations for 48 h, the level of SATB1 protein expression of MDA-MB-231 cel s decreased obviously, in a dose-dependent manner (P<0.05). Conclusion:Baicalein inhibits breast cancer cel proliferation and suppresses its invasion and metastasis by reducing cel migration possibly by down-regulation of the SATB1 protein expression, indicating that baicalein is a potential therapeutic agent for human breast cancer.

  7. [Effects of mammalian-target-of-rapamycin pathway on lapatinib resistance in breast cancer MDA-MB-231 cells].

    Science.gov (United States)

    Wang, Jian-dong; Wang, Quan-sheng; Bai, Yi-zhou; Kou, De-qiang; Li, Xi-ru; Chen, Lin; Li, Rong

    2013-06-25

    To establish a lapatinib resistance cell line for elucidating the mechanisms of drug resistance of lapatinib in human breast cancer cells. The human breast cancer MDA-MB-231 cells were exposed in an incremental dose of lapatinib to establish a lapatinib resistance rMDA-MB-231 cell line. The assay of methyl thiazolyl tetrazolium (MTT) was used to detect the cytotoxic activity of lapatinib against MDA-MB-231 and rMDA-MB-231 cells. The protein expression was detected by Western blot. Small interfering RNA was used to specifically knock down mammalian-target-of-rapamycin (mTOR) in rMDA-MB-231 cells. Apoptosis was determined by fluorescein isothiocyanate (FITC)-annexin V/PI staining and flow cytometry. The human breast cancer lapatinib resistance cell line rMDA-MB-231 was induced by lapatinib. The half maximal inhibitory concentration (IC50) values of lapatinib against MDA-MB-231 and rMDA-MB-231 cells were (6.1 ± 0.6) and (34.9 ± 2.7) µmol/L respectively (P MB-231 cells, the protein expression of mTOR in rMDA-MB-231 cells was significantly up-regulated. The protein expression of mTOR was significantly down-regulated by specific siRNA duplexes in rMDA-MB-231 cells. After siRNA interference, 20 µmol/L lapatinib was added into control, negative siRNA control and mTOR-targeted siRNA groups respectively. The percents of cell apoptosis in control, negative control and targeted siRNA groups were 13.4% ± 2.5%, 14.2% ± 2.8% and 34.6% ± 5.8% respectively, there was no significance between the first two groups (P > 0.05) , and there was significant difference between the control and targeted siRNA group (P MB-231 cells. And the down-regulation of mTOR increases the apoptotic death of lapatinib against rMDA-MB-231 cells.

  8. Optical Identifications of Companion Soft X-ray Sources of Mrk 231

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    We present optical identification results for four ROSAT PSPC soft X-ray companions of Mrk 231 based on the deep BATC 6660 A-band image and the optical spectra obtained by the 60/90cm Schmidt telescope and the 2.16mtelescope at the Xinglong Station, NAOC. Three optical counterparts are quasarswith redshifts z > 1 and the remaining X-ray source is probably a background galaxycluster. Therefore, none of these soft X-ray companions are physically connectedwith the central X-ray source Mrk 231. Incorporating the previous results of Arp 220and Mrk 273 (Xia et al. 1998, 1999), we suggest that the apparent soft X-rayassociations with ULIRGs are chance coincidence in most cases.

  9. Thr175-phosphorylated tau induces pathologic fibril formation via GSK3β-mediated phosphorylation of Thr231 in vitro.

    Science.gov (United States)

    Moszczynski, Alexander J; Gohar, May; Volkening, Kathryn; Leystra-Lantz, Cheryl; Strong, Wendy; Strong, Michael J

    2015-03-01

    We have previously shown that amyotrophic lateral sclerosis with cognitive impairment can be characterized by pathologic inclusions of microtubule-associated protein tau (tau) phosphorylated at Thr(175) (pThr(175)) in association with GSK3β activation. We have now examined whether pThr(175) induces GSK3β activation and whether this leads to pathologic fibril formation through Thr(231) phosphorylation. Seventy-two hours after transfection of Neuro2A cells with pseudophosphorylated green fluorescent protein-tagged 2N4R tau (Thr(175)Asp), phosphorylated kinase glycogen synthase kinase 3 beta (active GSK3β) levels were significantly increased as was pathologic fibril formation and cell death. Treatment with each of 4 GSK3β inhibitors or small hairpin RNA knockdown of GSK3β abolished fibril formation and prevented cell death. Inhibition of Thr(231) phosphorylation (Thr(231)Ala) prevented pathologic tau fibril formation, regardless of Thr(175) state, whereas Thr(231)Asp (pseudophosphorylated at Thr(231)) developed pathologic tau fibrils. Ser(235) mutations did not affect fibril formation, indicating an unprimed mechanism of Thr(231) phosphorylation. These findings suggest a mechanism of tau pathology by which pThr(175) induces GSK3β phosphorylation of Thr(231) leading to fibril formation, indicating a potential therapeutic avenue for amyotrophic lateral sclerosis with cognitive impairment. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Interfering with CXCR4 expression inhibits proliferation, adhesion and migration of breast cancer MDA-MB-231 cells.

    Science.gov (United States)

    Guo, Shanyu; Xiao, Dan; Liu, Huihui; Zheng, Xiao; Liu, Lei; Liu, Shougui

    2014-10-01

    To investigate the effect and mechanism of the CXC chemokine receptor 4 (CXCR4) in the proliferation and migration of breast cancer, a short-hairpin RNA (shRNA) eukaryotic expression vector targeting CXCR4 was constructed, and the impact of such on the proliferation, adhesion and migration of human breast cancer MDA-MB-231 cells was observed. The fragments of CXCR4-shRNA were synthesized and cloned into a pGCsi-U6-Neo-green fluorescent protein vector. The recombinant plasmids were transfected into 293T cells and the most efficacious interfering vector was selected. MDA-MB-231 cells were transfected by liposome assay. The effects of silencing CXCR4 expression by shRNA on the growth, adhesion and migration of MDA-MB-231 cells were determined by Cell Counting Kit-8, cell-matrix adhesion and wound-healing assays. The shRNA eukaryotic expression vectors targeting CXCR4 (CXCR4-shRNA) were successfully constructed and transfected into 293T cells. Quantitative polymerase chain reaction and western blot analysis revealed that the maximum inhibitory rate of CXCR4 expression was 81.3%. CXCR4-shRNA transfection significantly inhibited the proliferation of MDA-MB-231 cells (PMB-231 cells and the extracellular matrix (PMB-231 cells in the CXCR4-shRNA transfection group was significantly smaller than that in the control plasmid and blank control groups (PMB-231 cells.

  11. Radiation protection potential of MOX-fuel doped with 231Pa and Cs radioisotopes.

    Science.gov (United States)

    Kryuchkov, E F; Glebov, V B; Apse, V A; Shmelev, A N

    2005-01-01

    The paper addresses the problem of MOX-fuel self-protection during full cycle of MOX-fuel management. Under conditions of the closed LWR cycle the proliferation-resistance levels were evaluated for fresh and spent MOX-fuel with 231Pa and Cs feed. As it follows from the paper results, combination of these two admixtures being doped into MOX-fuel is able to enhance the inherent radiation barrier and to weaken shortcomings of both proliferation deterrents.

  12. Frankincense derived heavy terpene cocktail boosting breast cancer cell(MDA-MB-231) death in vitro简

    Institute of Scientific and Technical Information of China (English)

    Faruck; Lukmanul; Hakkim; Mohammed; Al-Buloshi; Jamal; Al-Sabahi

    2015-01-01

    Objective: To investigate the anti-cancer effect of frankincense derived heavy oil obtained by Soxhlet extraction method on breast cancer cells(MDA-MB-231), and to study its chemical profile using gas chromatography mass spectrometry analysis.Methods: Hexane was used to extract heavy oil from frankincense resin. Chemical profiling of heavy oil was done using Perkin Elmer Clarus GC system with mass spectrometer. MDA-MB-231 cells were treated with different dilutions(1:1 000, 1:1 500,1:1 750, 1:2 000, 1:2 250, 1:2 500, 1:2 750, 1:3 000, 1:3 250) of heavy oil for 24 h. The cells were observed by using light microscopy. Cell viability was measured by MTT assay.Results: Gas chromatography mass spectrometry chemical profiling of frankincense derived heavy oil revealed the presence of terpenes such as a-pinene(61.56%), a-amyrin(20.6%), b-amyrin(8.1%), b-phellandrene(1.47%) and camphene(1.04%). Heavy terpene cocktail induced significant MDA-MB-231 cell death at each concentration tested. Noticeably, very low concentration of Soxhlet derived heavy terpenes elicits considerable cytotoxicity on MDA-MB-231 cells compared to hydro distillated essential oil derived from frankincense resin.Conclusions: Extracting anti-cancer active principle cocktail by simple Soxhlet method is cost effective and less time consuming. Our in vitro anti-cancer data forms the rationale for us to test heavy terpene complex in breast cancer xenograft model in vivo. Furthermore, fractionation and developing frankincense heavy terpene based breast cancer drug is the major goal of our laboratory.

  13. Frankincense derived heavy terpene cocktail boosting breast cancer cell (MDA-MB-231) deathin vitro

    Institute of Scientific and Technical Information of China (English)

    Faruck Lukmanul Hakkim; Mohammed Al-Buloshi; Jamal Al-Sabahi

    2015-01-01

    Objective:To investigate the anti-cancer effect of frankincense derived heavy oil obtained by Soxhlet extraction method on breast cancer cells (MDA-MB-231), and to study its chemical profile using gas chromatography mass spectrometry analysis. Methods: Hexane was used to extract heavy oil from frankincense resin. Chemical profiling of heavy oil was done using Perkin Elmer Clarus GC system with mass spectrometer.MDA-MB-231 cells were treated with different dilutions (1:1 000, 1:1 500, 1:1 750, 1:2 000, 1:2 250, 1:2 500, 1:2 750, 1:3 000, 1:3 250) of heavy oil for 24 h. The cells were observed by using light microscopy. Cell viability was measured byMTT assay. Results: Gas chromatography mass spectrometry chemical profiling of frankincense derived heavy oil revealed the presence of terpenes such asα-pinene (61.56%),α-amyrin (20.6%),β-amyrin (8.1%),β-phellandrene (1.47%) and camphene (1.04%). Heavy terpene cocktail induced significantMDA-MB-231 cell death at each concentration tested. Noticeably, very low concentration of Soxhlet derived heavy terpenes elicits considerable cytotoxicityon MDA-MB-231cells compared to hydro distillated essential oil derived from frankincense resin. Conclusions: Extracting anti-cancer active principle cocktail by simple Soxhlet method is cost effective and less time consuming. Ourin vitro anti-cancer data forms the rationale for us to test heavy terpene complex in breast cancer xenograft modelin vivo. Furthermore, fractionation and developing frankincense heavy terpene based breast cancer drug is the major goal of our laboratory.

  14. Mitochondrial calcium uniporter activity is dispensable for MDA-MB-231 breast carcinoma cell survival.

    Science.gov (United States)

    Hall, Duane D; Wu, Yuejin; Domann, Frederick E; Spitz, Douglas R; Anderson, Mark E

    2014-01-01

    Calcium uptake through the mitochondrial Ca2+ uniporter (MCU) is thought to be essential in regulating cellular signaling events, energy status, and survival. Functional dissection of the uniporter is now possible through the recent identification of the genes encoding for MCU protein complex subunits. Cancer cells exhibit many aspects of mitochondrial dysfunction associated with altered mitochondrial Ca2+ levels including resistance to apoptosis, increased reactive oxygen species production and decreased oxidative metabolism. We used a publically available database to determine that breast cancer patient outcomes negatively correlated with increased MCU Ca2+ conducting pore subunit expression and decreased MICU1 regulatory subunit expression. We hypothesized breast cancer cells may therefore be sensitive to MCU channel manipulation. We used the widely studied MDA-MB-231 breast cancer cell line to investigate whether disruption or increased activation of mitochondrial Ca2+ uptake with specific siRNAs and adenoviral overexpression constructs would sensitize these cells to therapy-related stress. MDA-MB-231 cells were found to contain functional MCU channels that readily respond to cellular stimulation and elicit robust AMPK phosphorylation responses to nutrient withdrawal. Surprisingly, knockdown of MCU or MICU1 did not affect reactive oxygen species production or cause significant effects on clonogenic cell survival of MDA-MB-231 cells exposed to irradiation, chemotherapeutic agents, or nutrient deprivation. Overexpression of wild type or a dominant negative mutant MCU did not affect basal cloning efficiency or ceramide-induced cell killing. In contrast, non-cancerous breast epithelial HMEC cells showed reduced survival after MCU or MICU1 knockdown. These results support the conclusion that MDA-MB-231 breast cancer cells do not rely on MCU or MICU1 activity for survival in contrast to previous findings in cells derived from cervical, colon, and prostate cancers and

  15. Mitochondrial calcium uniporter activity is dispensable for MDA-MB-231 breast carcinoma cell survival.

    Directory of Open Access Journals (Sweden)

    Duane D Hall

    Full Text Available Calcium uptake through the mitochondrial Ca2+ uniporter (MCU is thought to be essential in regulating cellular signaling events, energy status, and survival. Functional dissection of the uniporter is now possible through the recent identification of the genes encoding for MCU protein complex subunits. Cancer cells exhibit many aspects of mitochondrial dysfunction associated with altered mitochondrial Ca2+ levels including resistance to apoptosis, increased reactive oxygen species production and decreased oxidative metabolism. We used a publically available database to determine that breast cancer patient outcomes negatively correlated with increased MCU Ca2+ conducting pore subunit expression and decreased MICU1 regulatory subunit expression. We hypothesized breast cancer cells may therefore be sensitive to MCU channel manipulation. We used the widely studied MDA-MB-231 breast cancer cell line to investigate whether disruption or increased activation of mitochondrial Ca2+ uptake with specific siRNAs and adenoviral overexpression constructs would sensitize these cells to therapy-related stress. MDA-MB-231 cells were found to contain functional MCU channels that readily respond to cellular stimulation and elicit robust AMPK phosphorylation responses to nutrient withdrawal. Surprisingly, knockdown of MCU or MICU1 did not affect reactive oxygen species production or cause significant effects on clonogenic cell survival of MDA-MB-231 cells exposed to irradiation, chemotherapeutic agents, or nutrient deprivation. Overexpression of wild type or a dominant negative mutant MCU did not affect basal cloning efficiency or ceramide-induced cell killing. In contrast, non-cancerous breast epithelial HMEC cells showed reduced survival after MCU or MICU1 knockdown. These results support the conclusion that MDA-MB-231 breast cancer cells do not rely on MCU or MICU1 activity for survival in contrast to previous findings in cells derived from cervical, colon, and

  16. Neem Seed Oil Induces Apoptosis in MCF-7 and MDA MB-231 Human Breast Cancer Cells

    Science.gov (United States)

    Sharma, Ramesh; Kaushik, Shweta; Shyam, Hari; Agarwal, Satish; Balapure, Anil Kumar

    2017-08-27

    Background: In traditional Indian medicine, azadirachta indica (neem) is known for its wide range of medicinal properties. Various parts of neem tree including its fruit, seed, bark, leaves, and root have been shown to possess antiseptic, antiviral, antipyretic, anti-inflammatory, antiulcer, antimalarial, antifungal and anticancer activity. Materials and Methods: MCF-7 and MDA MB-231 cells were exposed to various concentrations of 2% ethanolic solution of NSO (1-30 μl/ml) and further processed for cell viability, cell cycle and apoptosis analysis. In addition, cells were analyzed for alteration in Mitochondrial Membrane Potential (MMP) and generation of Reactive Oxygen Species (ROS) using JC-1 and DCFDA staining respectively. Results: NSO give 50% inhibition at 10 μl/ml and 20 μl/ml concentration in MCF-7 and MDA MB-231 cells respectively and, arrests cells at G0/G1 phase in both the cell types. There was a significant alteration in mitochondrial membrane potential that leads to the generation of ROS and induction of apoptosis in NSO treated MCF-7 and MDA MB-231 cells. Conclusion: The results showed that NSO inhibits the growth of human breast cancer cells via induction of apoptosis and G1 phase arrest. Collectively these results suggest that NSO could potentially be used in the management of breast cancer. Creative Commons Attribution License

  17. Cytotoxicity of Biologically Synthesized Silver Nanoparticles in MDA-MB-231 Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Sangiliyandi Gurunathan

    2013-01-01

    Full Text Available Silver nanoparticles (AgNPs have been used as an antimicrobial and disinfectant agents. However, there is limited information about antitumor potential. Therefore, this study focused on determining cytotoxic effects of AgNPs on MDA-MB-231 breast cancer cells and its mechanism of cell death. Herein, we developed a green method for synthesis of AgNPs using culture supernatant of Bacillus funiculus, and synthesized AgNPs were characterized by various analytical techniques such as UV-visible spectrophotometer, particle size analyzer, and transmission electron microscopy (TEM. The toxicity was evaluated using cell viability, metabolic activity, and oxidative stress. MDA-MB-231 breast cancer cells were treated with various concentrations of AgNPs (5 to 25 μg/mL for 24 h. We found that AgNPs inhibited the growth in a dose-dependent manner using MTT assay. AgNPs showed dose-dependent cytotoxicity against MDA-MB-231 cells through activation of the lactate dehydrogenase (LDH, caspase-3, reactive oxygen species (ROS generation, eventually leading to induction of apoptosis which was further confirmed through resulting nuclear fragmentation. The present results showed that AgNPs might be a potential alternative agent for human breast cancer therapy.

  18. Holocene Paleocirculation from 231Pa/230Th in Sediments from the North Atlantic Ocean

    Science.gov (United States)

    McManus, J.; Francois, R.; Major, C.; Gherardi, J.; Hoffman, S.

    2004-12-01

    A new record of bulk sedimentary 231Pa/230Th excesses from core GGC5 on the Bermuda Rise has been produced by ICP-MS. The record reveals several aspects of the strength of the meridional overturning circulation during the last ten thousand years. Measurements of uranium, protactinium and thorium in the Holocene section recovered in GGC5 have been resolved at approximately 200-300 years, similar to the response time of excess 231Pa in the water column, and therefore should capture any large departure from modern values in the 231Pa/230Th indicator of paleocirculation. No dramatic increase in ratio or decrease in circulation is indicated by the data, which suggest vigorous overturning in the western basin of the North Atlantic since the end of the Younger Dryas. Instead of large changes in circulation, a series of oscillations punctuates the middle Holocene, indicating a variability of 10-20 percent in the rate of meridional overturning. Specific attention will be paid to millennial events postulated at 8.2 kyr, ~5 kyr, and in the most recent Holocene.

  19. Disparate SAR Data of Griseofulvin Analogues for the Dermatophytes Trichophyton mentagrophytes, T. rubrum, and MDA-MB-231 Cancer Cells

    DEFF Research Database (Denmark)

    Rønnest, Mads Holger; Raab, Marc S.; Anderhub, Simon

    2012-01-01

    Griseofulvin and 53 analogues of this compound have been tested against the pathogenic dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes as well as against the breast cancer cell line MDA-MB-231. The modifications to griseofulvin include the 4, 5, 6, 2', 3', and 4' positions...... of analogues showed increased activity against the cancer cell line MDA-MB-231, highlighted by 2'-benzyloxy-2'-demethoxy-griseofulvin, which showed low activity against both fungi but was among the most potent compounds against MDA-MB-231 cancer cells. Tubulin has been proposed as the target of griseofulvin...

  20. 49 CFR 231.25 - Track motorcars (self-propelled 4-wheel cars which can be removed from the rails by men).

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Track motorcars (self-propelled 4-wheel cars which can be removed from the rails by men). 231.25 Section 231.25 Transportation Other Regulations Relating... SAFETY APPLIANCE STANDARDS § 231.25 Track motorcars (self-propelled 4-wheel cars which can be...

  1. 巴西橡胶树TIM23-1基因克隆、进化及表达分析%Cloning, Phylogenetic and Expression Analyses ofTIM23-1 Gene inHevea brasiliensis

    Institute of Scientific and Technical Information of China (English)

    陈江淑; 邓治; 刘辉; 范玉龙; 姜达; 夏立琼; 夏志辉; 李德军

    2015-01-01

    In this study, a full-length cDNA sequence ofTIM23 gene was cloned fromHevea brasiliensis with the rapid-ampliifcation of cDNA ends (RACE) method, and the gene was named asHbTIM23-1. The full length cDNA ofHbTIM23-1 is 898 bpin size with a 567 bpopen reading frame,encoding a deduced polypeptide of 188 amino acids. The deduced HbTIM23-1 contains a predicted transmembrane region and preprotein and ami-no acid transporter (PRAT) domain and indicates high identity to AtTIM23-1 protein. Real-time RT-PCR anal-yses indicated thatHbTIM23-1 was expressed in latex, barks, leaves, barks, male lfowers, female lfowers and anthers. With the development of leaves, theHbTIM23-1 expression showed a signiifcant change. Compared with healthy rubber tree,HbTIM23-1 was down-regulated in tapping panel dryness (TPD) rubber tree latex. The expression of HbTIM23-1 was regulated by drought and low temperature treatments, suggesting thatHb-TIM23-1 might play important roles in drought and low temperature responses as well as TPD inH. brasiliensis.%本研究采用RACE技术,从巴西橡胶树中鉴定出一个线粒体内膜转位因子TIM23基因。该基因全长cDNA为898 bp,最长开放阅读框567 bp,预测编码蛋白包含188个氨基酸;序列比对分析发现,该基因编码蛋白具有转膜区和PRAT结构域,与拟南芥TIM23-1蛋白具有较高的相似性,将该基因命名为HbTIM23-1。实时定量RT-PCR分析结果表明, HbTIM23-1在巴西橡胶树胶乳、叶片、树皮、雄花、雌花、花药中均有表达。在橡胶树叶片不同发育时期, HbTIM23-1表达存在变化。与健康橡胶树相比,死皮橡胶树胶乳中HbTIM23-1表达量明显下降。研究发现HbTIM23-1表达受干旱和低温处理调控,表明Hb-TIM23-1可能在巴西橡胶树干旱和低温胁迫应答及死皮中发挥作用。

  2. Persistent export of 231Pa from the deep central Arctic Ocean over the past 35,000 years.

    Science.gov (United States)

    Hoffmann, Sharon S; McManus, Jerry F; Curry, William B; Brown-Leger, L Susan

    2013-05-30

    The Arctic Ocean has an important role in Earth's climate, both through surface processes such as sea-ice formation and transport, and through the production and export of waters at depth that contribute to the global thermohaline circulation. Deciphering the deep Arctic Ocean's palaeo-oceanographic history is a crucial part of understanding its role in climatic change. Here we show that sedimentary ratios of the radionuclides thorium-230 ((230)Th) and protactinium-231 ((231)Pa), which are produced in sea water and removed by particle scavenging on timescales of decades to centuries, respectively, record consistent evidence for the export of (231)Pa from the deep Arctic and may indicate continuous deep-water exchange between the Arctic and Atlantic oceans throughout the past 35,000 years. Seven well-dated box-core records provide a comprehensive overview of (231)Pa and (230)Th burial in Arctic sediments during glacial, deglacial and interglacial conditions. Sedimentary (231)Pa/(230)Th ratios decrease nearly linearly with increasing water depth above the core sites, indicating efficient particle scavenging in the upper water column and greater influence of removal by lateral transport at depth. Although the measured (230)Th burial is in balance with its production in Arctic sea water, integrated depth profiles for all time intervals reveal a deficit in (231)Pa burial that can be balanced only by lateral export in the water column. Because no enhanced sink for (231)Pa has yet been found in the Arctic, our records suggest that deep-water exchange through the Fram strait may export (231)Pa. Such export may have continued for the past 35,000 years, suggesting a century-scale replacement time for deep waters in the Arctic Ocean since the most recent glaciation and a persistent contribution of Arctic waters to the global ocean circulation.

  3. Chromosome 8p23.1 deletions as a cause of complex congenital heart defects and diaphragmatic hernia.

    Science.gov (United States)

    Wat, Margaret J; Shchelochkov, Oleg A; Holder, Ashley M; Breman, Amy M; Dagli, Aditi; Bacino, Carlos; Scaglia, Fernando; Zori, Roberto T; Cheung, Sau Wai; Scott, Daryl A; Kang, Sung-Hae Lee

    2009-08-01

    Recurrent interstitial deletion of a region of 8p23.1 flanked by the low copy repeats 8p-OR-REPD and 8p-OR-REPP is associated with a spectrum of anomalies that can include congenital heart malformations and congenital diaphragmatic hernia (CDH). Haploinsufficiency of GATA4 is thought to play a critical role in the development of these birth defects. We describe two individuals and a monozygotic twin pair discordant for anterior CDH all of whom have complex congenital heart defects caused by this recurrent interstitial deletion as demonstrated by array comparative genomic hybridization. To better define the genotype/phenotype relationships associated with alterations of genes on 8p23.1, we review the spectrum of congenital heart and diaphragmatic defects that have been reported in individuals with isolated GATA4 mutations and interstitial, terminal, and complex chromosomal rearrangements involving the 8p23.1 region. Our findings allow us to clearly define the CDH minimal deleted region on chromosome 8p23.1 and suggest that haploinsufficiency of other genes, in addition to GATA4, may play a role in the severe cardiac and diaphragmatic defects associated with 8p23.1 deletions. These findings also underscore the importance of conducting a careful cytogenetic/molecular analysis of the 8p23.1 region in all prenatal and postnatal cases involving congenital defects of the heart and/or diaphragm.

  4. Chromosome 8p23.1 Deletions as a Cause of Complex Congenital Heart Defects and Diaphragmatic Hernia

    Science.gov (United States)

    Wat, Margaret J.; Shchelochkov, Oleg A.; Holder, Ashley M.; Breman, Amy M.; Dagli, Aditi; Bacino, Carlos; Scaglia, Fernando; Zori, Roberto T.; Cheung, Sau Wai; Scott, Daryl A.; Kang, Sung-Hae Lee

    2009-01-01

    Recurrent interstitial deletion of a region of 8p23.1 flanked by the low copy repeats 8p-OR-REPD and 8p-OR-REPP is associated with a spectrum of anomalies that can include congenital heart malformations and congenital diaphragmatic hernia (CDH). Haploinsufficiency of GATA4 is thought to play a critical role in the development of these birth defects. We describe two individuals and a monozygotic twin pair discordant for anterior CDH all of whom have complex congenital heart defects caused by this recurrent interstitial deletion as demonstrated by array comparative genome hybridization. To better define the genotype/phenotype relationships associated with alterations of genes on 8p23.1, we review the spectrum of congenital heart and diaphragmatic defects that have been reported in individuals with isolated GATA4 mutations and interstitial, terminal, and complex chromosomal rearrangements involving the 8p23.1 region. Our findings allow us to clearly define the CDH minimal deleted region on chromosome 8p23.1 and suggest that haploinsufficiency of other genes, in addition to GATA4, may play a role in the severe cardiac and diaphragmatic defects associated with 8p23.1 deletions. These findings also underscore the importance of conducting a careful cytogenetic/molecular analysis of the 8p23.1 region in all prenatal and postnatal cases involving congenital defects of the heart and/or diaphragm. PMID:19606479

  5. Glutamine deprivation sensitizes human breast cancer MDA-MB-231 cells to TRIAL-mediated apoptosis.

    Science.gov (United States)

    Dilshara, Matharage Gayani; Jeong, Jin-Woo; Prasad Tharanga Jayasooriya, Rajapaksha Gedara; Neelaka Molagoda, Ilandarage Menu; Lee, Seungheon; Park, Sang Rul; Choi, Yung Hyun; Kim, Gi-Young

    2017-02-13

    Tumor cell metabolism is a promising target for various cancer treatments. Apart from aerobic glycolysis, cancer cell growth is dependent on glutamine (Gln) supply, leading to their survival and differentiation. Therefore, we examined whether treatment with TNF-related apoptosis-inducing ligand (TRAIL) sensitizes MDA-MB-231 cells to apoptosis under Gln deprivation condition (TRAIL/Gln deprivation). Gln deprivation decreased cell proliferation as expected, but did not induce remarkable cell death. TRAIL/Gln deprivation, however, significantly increased growth inhibition and morphological shrinkage of MDA-MB-231 cells compared to those induced by treatment with either Gln deprivation or TRAIL alone. Moreover, TRAIL/Gln deprivation upregulated the apoptotic sub-G1 phase accompanied with a remarkable decrease of pro-caspase-3, pro-caspase-9, and anti-apoptotic xIAP, and Bcl-2. Increased cleavage of PARP and pro-apoptotic Bid protein expression suggests that TRAIL/Gln deprivation triggers mitochondrion-mediated apoptosis in MDA-MB-231 cells. Additionally, TRAIL/Gln deprivation upregulated the expression of endoplasmic reticulum (ER) stress markers such as ATF4 and phosphorylated eIF2α, thereby enhancing the C/EBP homologous protein (CHOP) protein level. Transient knockdown of CHOP partically reversed TRAIL/Gln deprivation-mediated apoptosis. Accordingly, TRAIL/Gln deprivation enhanced the expression of death receptor 5 (DR5) and transient knockdown of DR5 completely restored TRAIL/Gln deprivation-mediated apoptosis. Taken together, our results suggest that Gln deprivation conditions can be used for the development of new therapies for TRAIL-resistant cancers.

  6. [Genital ulcers in French Guyana. Apropos of 231 cases screened in 2 years].

    Science.gov (United States)

    Crenn, Y; Zeller, H; Pradinaud, R; Sainte-Marie, D

    1988-01-01

    In fight against Sexually Transmitted Diseases (STD), 231 cases of genital ulcers were observed, in 1985 and 1986, in Cayenne (French Guiana) according to a clinical and laboratory study protocol described by the authors. The diagnosis shown, in 146 cases, one STD agent, with a high frequency of chancroid, herpes genitalis and primary syphilis. In addition, 18 cases of mixed genital infections are described: emphasis is laid on the great diversity of these associated diseases. 67 genital ulcers had not been caused by a STD agent, however in each case a complete laboratory investigation was done, and each patient received a treatment according to the diagnosis.

  7. Influence of {sup 231}Th in the activity determination of {sup 234}Th by Cerenkov counting

    Energy Technology Data Exchange (ETDEWEB)

    Blasiyh Nuno, G.A. [Programa Nacional de Gestion de Residuos Radiactivos, Comision Nacional de Energia Atomica, Centro Atomico Ezeiza, Presbitero Juan Gonzalez, y Aragon No. 15, B1802AYA, Partido de Ezeiza, Provincia de Buenos Aires (Argentina)]. E-mail: blasiyh@cae.cnea.gov.ar; Korob, R.O. [Unidad de Actividad Radioquimica y Quimica de las Radiaciones, Comision Nacional de Energia Atomica, Centro Atomico Ezeiza, Presbitero Juan Gonzalez, y Aragon No. 15, B1802AYA, Partido de Ezeiza, Provincia de Buenos Aires (Argentina)

    2007-05-15

    A precise and simple method for the determination of {sup 234}Th activity by Cerenkov counting is described. A calibrated natural uranium solution (having {sup 234m}Pa and {sup 238}U in secular equilibrium) in 0.1 M HNO{sub 3} is used to construct the calibration curve. Because {sup 231}Th (a {beta}-emitting nuclide present in the decay chain of {sup 235}U) contribution to Cerenkov counting is experimentally proved to be negligible only in the case of low enriched uranium samples, simple calculations are needed to accomplish the activity determination.

  8. Molecular Emission in Dense Massive Clumps from the Star-Forming Regions S231-S235

    CERN Document Server

    Ladeyschikov, D A; Tsivilev, A P; Sobolev, A M

    2016-01-01

    The article deals with observations of star-forming regions S231-S235 in 'quasi-thermal' lines of ammonia (NH$_3$), cyanoacetylene (HC$_3$N) and maser lines of methanol (CH$_3$OH) and water vapor (H$_2$O). S231-S235 regions is situated in the giant molecular cloud G174+2.5. We selected all massive molecular clumps in G174+2.5 using archive CO data. For the each clump we determined mass, size and CO column density. After that we performed observations of these clumps. We report about first detections of NH$_3$ and HC$_3$N lines toward the molecular clumps WB89 673 and WB89 668. This means that high-density gas is present there. Physical parameters of molecular gas in the clumps were estimated using the data on ammonia emission. We found that the gas temperature and the hydrogen number density are in the ranges 16-30 K and 2.8-7.2$\\times10^3$ cm$^{-3}$, respectively. The shock-tracing line of CH$_3$OH molecule at 36.2 GHz is newly detected toward WB89 673.

  9. Another piece of the puzzle: the fast HI outflow in Mrk231

    CERN Document Server

    Morganti, Raffaella; Oosterloo, Tom; Teng, Stacy H; Rupke, David

    2016-01-01

    We present the detection, performed with the Westerbork Synthesis Radio Telescope (WSRT) and the Karl Jansky Very Large Array (VLA), of a fast HI 21-cm outflow in the ultra-luminous infrared galaxy Mrk 231. The outflow is observed as shallow HI absorption blueshifted ~1300 km/s with respect to the systemic velocity and located against the inner kpc of the radio source. The outflowing gas has an estimated column density between 5 and 15x10^18 Tspin cm^-2. We derive the Tspin to lie in the range 400-2000 K and the densities are n_HI~10-100 cm^-3. Our results confirm the multiphase nature of the outflow in Mrk231. Although effects of the interaction between the radio plasma and the surrounding medium cannot be ruled out, the energetics and the lack of a clear kpc-scale jet suggest that the most likely origin of the HI outflow is a wide-angle nuclear wind, as earlier proposed to explain the neutral outflow traced by NaI and molecular gas. Our results suggest that an HI component is present in fast outflows regard...

  10. Cadmium effects on p38/MAPK isoforms in MDA-MB231 breast cancer cells.

    Science.gov (United States)

    Casano, Caterina; Agnello, Maria; Sirchia, Rosalia; Luparello, Claudio

    2010-02-01

    Emerging evidence seems to indicate that the heavy metal cadmium (Cd) is able to regulate gene expression, drastically affecting the pattern of transcriptional activity in normal and pathological eukaryotic cells, also affecting intracellular signalization events. Human p38 is a family of mitogen-activated protein kinases consisting of four isoforms (alpha, beta, gamma and delta) which mediate signal transduction cascades controlling several aspects of cell physiology. In this study we examined whether exposure of MDA-MB231 tumor cells from the human breast to Cd may exert some effect on p38 isoform expression and accumulation, as well as on p38 activation. Employing a combination of proliferation tests, conventional and semiquantitative multiplex (SM)-polymerase chain reaction (PCR) and Western blot assays, we report that the treatment of breast cancer cells with 5 microM CdCl(2) induces a diversified modulation of the transcription patterns of p38 isoform genes and of the accumulation of the related protein products, which are, on the other hand, also affected by alpha and beta isoform functional inactivation induced by SB203580. Our findings suggest the existence of so far unexplored mechanisms of gene regulation in our model system and validate that MDA-MB231 cell line is a suitable in vitro model for further and more detailed studies on the intracellular mechanisms underlying the control of p38 expression, synthesis and activation in mammary tumor cells exposed to different stresses.

  11. TMEM231 Gene Conversion Associated with Joubert and Meckel-Gruber Syndromes in the Same Family.

    Science.gov (United States)

    Maglic, Dino; Stephen, Joshi; Malicdan, May Christine V; Guo, Jennifer; Fischer, Roxanne; Konzman, Daniel; Mullikin, James C; Gahl, William A; Vilboux, Thierry; Gunay-Aygun, Meral

    2016-11-01

    Joubert and Meckel-Gruber syndromes (JS and MGS) are ciliopathies with overlapping features. JS patients manifest the "molar tooth sign" on brain imaging and variable eye, kidney, and liver disease. MGS presents with polycystic kidneys, occipital encephalocele, and polydactyly; it is typically perinatally fatal. Both syndromes are genetically heterogeneous; some genes cause either syndrome. Here, we report two brothers married to unrelated women. The first brother had three daughters with JS and a son with polycystic kidneys who died at birth. The second brother's wife had a fetal demise due to MGS. Whole exome sequencing identified TMEM231 NM_001077416.2: c.784G>A; p.(Asp262Asn) in all children and the wife of the first brother; the second brother's wife had a c.406T>G;p.(Trp136Gly) change. In-depth analysis uncovered a rare gene conversion event in TMEM231, leading to loss of exon 4, in all the affected children of first brother. We believe that the combination of this gene conversion with different missense mutations led to a spectrum of phenotypes that span JS and MGS. © 2016 WILEY PERIODICALS, INC.

  12. Functional Expression of Voltage-Gated Sodium Channels Navl.5 in Human Breast Caner Cell Line MDA-MB-231

    Institute of Scientific and Technical Information of China (English)

    Rui GAO; Jing WANG; Yi SHEN; Ming LEI; Zehua WANG

    2009-01-01

    Voltage-gated sodium channels (VGSCs) are known to be involved in the initiation and progression of many malignancies,and the different subtypes of VGSCs play important roles in the metastasis cascade of many tumors.This study investigated the functional expression of Nav 1.5 and its effect on invasion behavior of human breast cancer cell line MDA-MB-231.The mRNA and pro-tein expression of Navl.5 was detected by real time PCR,Western Blot and immunofluorescence.The effects of Navl.5 on cell proliferation,migration and invasion were respectively assessed by MTT and Transwell.The effects of Nav1.5 on the secretion of matrix metalloproteases (MMPs) by MDA-MB-231 were analyzed by RT-PCR.The over-expressed Navl.5 was present on the membrane of MDA-MB-231 cells.The invasion ability in vitro and the MMP-9 mRNA expression were respec-tively decreased to (47.82±0.53)% and (43.97±0.64)% (P<0.05) respectively in MDA-MB-231 cells treated with VGSCs specific inhibitor tetrodotoxin (TTX) by blocking Navl.5 activity.It was con-eluded that Nav1.5 functional expression potentiated the invasive behavior of human breast cancer cell line MDA-MB-231 by increasing the secretion of MMP-9.

  13. [Inhibitory effects of capsaicin on migration and invasion of breast cancer MDA-MB-231 cells and its mechanism].

    Science.gov (United States)

    Li, Bai-He; Yuan, Lei

    2017-04-25

    The aim of this study was to investigate the effects of capsaicin on migration and invasion of breast cancer MDA-MB-231 cells and its possible mechanism. The MDA-MB-231 cells were incubated in the medium containing different concentrations of capsaicin for 24 h. CCK-8 assay was employed to detect the cell viability. The cell migration and invasion were assessed by wound healing assay and transwell invasion assay, respectively. The protein levels of c-Src, p-c-Src (Tyr416), FAK, p-FAK (Tyr576), Paxillin, p-Paxillin (Tyr118), matrix metalloproteinase 2 (MMP2) and MMP9 in the MDA-MB-231 cells were detected by Western blotting. The mRNA expressions of MMP2 and MMP9 were measured by RT-PCR. The result showed that capsaicin (25 and 50 μmol/L) remarkably reduced the abilities of migration and invasion (P MB-231 cells. These effects of capsaicin were all in dose-dependent manners. These results suggest that capsaicin may suppress the migration and invasion of breast cancer MDA-MB-231 cells by inhibiting the phosphorylations of c-Src, FAK and Paxillin, and down-regulating the mRNA and protein levels of MMP2 and MMP9.

  14. Intrinsic Resistance to 5-Fluorouracil in a Brain Metastatic Variant of Human Breast Cancer Cell Line, MDA-MB-231BR.

    Science.gov (United States)

    Sagara, Atsunobu; Igarashi, Katsuhide; Otsuka, Maky; Karasawa, Takeshi; Gotoh, Noriko; Narita, Michiko; Kuzumaki, Naoko; Narita, Minoru; Kato, Yoshinori

    2016-01-01

    Although drug resistance is often observed in metastatic recurrence of breast cancer, little is known about the intrinsic drug resistance in such metastases. In the present study, we found, for the first time, that MDA-MB-231BR, a brain metastatic variant of a human breast cancer cell line, was refractory to treatment with 5-fluorouracil (5-FU) even without chronic drug exposure, compared to its parent cell line, MDA-MB-231, and a bone metastatic variant, MDA-MB-231SCP2. Both the mRNA and protein levels of COX-2 and BCL2A1 in MDA-MB-231BR were significantly higher than those in MDA-MB-231 or MDA-MB-231SCP2. Neither the COX-2 inhibitor celecoxib nor the NF-κB inhibitor BAY11-7082 could sensitize MDA-MB-231BR to 5-FU, indicating that COX-2 plays little, if any, role in the resistance of MDA-MB-231BR to 5-FU. Although BCL2-family inhibitor ABT-263 failed to sensitize MDA-MB-231BR to 5-FU at a dose at which ABT-263 is considered to bind to BCL2, BCL2-xL, and BCL2-w, but not to BCL2A1, ABT-263 did sensitize MDA-MB-231BR to 5-FU to a level comparable to that in MDA-MB-231 at a dose of 5 μM, at which ABT-263 may disrupt intracellular BCL2A1 protein interactions. More importantly, BCL2A1 siRNA sensitized MDA-MB-231BR to 5-FU, whereas the overexpression of BCL2A1 conferred 5-FU-resistance on MDA-MB-231. These results indicate that BCL2A1 is a key contributor to the intrinsic 5-FU-resistance in MDA-MB-231BR. It is interesting to note that the drug sensitivity of MDA-MB-231BR was distinct from that of MDA-MB-231SCP2 even though they have the same origin (MDA-MB-231). Further investigations pertinent to the present findings may provide valuable insight into the breast cancer brain metastasis.

  15. Transcriptional program induced by factor VIIa-tissue factor, PAR1 and PAR2 in MDA-MB-231 cells

    DEFF Research Database (Denmark)

    Albrektsen, Tatjana; Sørensen, B B; Hjortø, G M

    2007-01-01

    -activated receptor 1 (PAR1) or PAR2 agonists using MDA-MB-231 breast carcinoma cells that constitutively express TF, PAR1 and PAR2. RESULTS AND CONCLUSIONS: Out of 8500 genes, FVIIa stimulation induced differential regulation of 39 genes most of which were not previously recognized as FVIIa regulated. All genes...... regulated genes encode cytokines, chemokines and growth factors, and the gene repertoire induced by FVIIa in MDA-MB-231 cells is consistent with a role for TF-FVIIa signaling in regulation of a wound healing type of response. Interestingly, a number of genes regulated exclusively by FVIIa/PAR2-mediated cell...... signaling in MDA-MB-231 cells were regulated by thrombin and a PAR1 agonist, but not by FVIIa, in the TF-expressing glioblastoma U373 cell line....

  16. Polyphenols from Artemisia annua L Inhibit Adhesion and EMT of Highly Metastatic Breast Cancer Cells MDA-MB-231.

    Science.gov (United States)

    Ko, Young Shin; Lee, Won Sup; Panchanathan, Radha; Joo, Young Nak; Choi, Yung Hyun; Kim, Gon Sup; Jung, Jin-Myung; Ryu, Chung Ho; Shin, Sung Chul; Kim, Hye Jung

    2016-07-01

    Recent evidence suggests that polyphenolic compounds from plants have anti-invasion and anti-metastasis capabilities. The Korean annual weed, Artemisia annua L., has been used as a folk medicine for treatment of various diseases. Here, we isolated and characterized polyphenols from Korean A. annua L (pKAL). We investigated anti-metastatic effects of pKAL on the highly metastatic MDA-MB-231 breast cancer cells especially focusing on cancer cell adhesion to the endothelial cell and epithelial-mesenchymal transition (EMT). Firstly, pKAL inhibited cell viability of MDA-MB-231 cells in a dose-dependent manner, but not that of human umbilical vein endothelial cells (ECs). Polyphenols from Korean A. annua L inhibited the adhesion of MDA-MB-231 cells to ECs through reducing vascular cell adhesion molecule-1 expression of MDA-MB-231 and ECs, but not intracellular adhesion molecule-1 at the concentrations where pKAL did not influence the cell viability of either MDA-MB-231 cells nor EC. Further, pKAL inhibited tumor necrosis factor-activated MDA-MB-231 breast cancer cell invasion through inhibition of matrix metalloproteinase-2 and matrix metalloproteinase-9 and EMT. Moreover, pKAL inhibited phosphorylation of Akt, but not that of protein kinase C. These results suggest that pKAL may serve as a therapeutic agent against cancer metastasis at least in part by inhibiting the cancer cell adhesion to ECs through suppression of vascular cell adhesion molecule-1 and invasion through suppression of EMT. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  17. Effect of Polygonatum odoratum extract on human breast cancer MDA-MB-231 cell proliferation and apoptosis.

    Science.gov (United States)

    Tai, Yu; Sun, Yi-Ming; Zou, Xue; Pan, Qiong; Lan, Ya-Dong; Huo, Qiang; Zhu, Jing-Wen; Guo, Fei; Zheng, Chang-Quan; Wu, Cheng-Zhu; Liu, Hao

    2016-10-01

    Traditional Chinese medicine (TCM) is important in the provision of anti-tumor drugs. Recently, studies have shown that certain types of TCM agents are able to control the growth of tumors, enhance the body's immune function and enhance the therapeutic effect of chemotherapeutic drugs. In women, breast carcinoma is the most common tumor type and the second most common cause of death from cancer. Polygonatum odoratum (P. odoratum) is commonly used in TCM. The aim of the present study was to investigate the effects of P. odoratum extract on the proliferation and apoptosis of MDA-MB-231 breast cancer cells. Cell proliferation was assessed using MTT and colony formation assays. In addition, propidium iodide (PI)/Annexin V-FITC staining was used to investigate the apoptosis of MDA-MB-231 cells following treatment with P. odoratum extract. The protein expression levels of B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) were also detected using western blot analysis, while a JC-1 staining assay was used to assess the mitochondrial membrane potential (ΔΨm). The results of the MTT assay showed that the proliferation and colony formation of MDA-MB-231 cells were inhibited following treatment with the extract. Furthermore, the PI/Annexin-V staining showed that the apoptosis of MDA-MB-231 cells was enhanced by the extract, in a concentration-dependent manner. The extract also lowered the ΔΨm of MDA-MB-231 cells, upregulated the expression of Bax and inhibited the expression of Bcl-2. In conclusion, these results showed that the P. odoratum extract inhibited the proliferation and induced apoptosis of breast cancer MDA-MB-231 cells.

  18. XMM-Newton Observation of Fe K(alpha) Emission from a BAL QSO: Mrk 231

    Science.gov (United States)

    Turner, T. J.; Kraemer, S. B.

    2003-01-01

    We present results from a 20 ksec XMM-Newton observation of Mrk 231. EPIC spectral data reveal strong line emission due to Fe K alpha, which has rarely been detected in this class, as BAL QSOs are very faint in the X-ray band. The line energy is consistent with an origin in neutral Fe. The width of the line is equivalent to a velocity dispersion approximately 18,000 kilometers per second and thus the line may be attributed to transmission and/or reflection from a distribution of emitting clouds. If, instead, the line originates in the accretion disk then the line strength and flat X-ray continuum support some contribution from a reflected component, although the data disfavor a model where the hard X-ray band is purely reflected X-rays. The line parameters are similar to those obtained for the Fe Ka line detected in another BAL QSO, H1413 + 117.

  19. Cell cycle arrest induced by MPPa-PDT in MDA-MB-231 cells

    Science.gov (United States)

    Liang, Liming; Bi, Wenxiang; Tian, Yuanyuan

    2016-05-01

    Photodynamic therapy (PDT) is a medical treatment using a photosensitizing agent and light source to treat cancers. Pyropheophorbidea methyl ester (MPPa), a derivative of chlorophyll, is a novel potent photosensitizer. To learn more about this photosensitizer, we examined the cell cycle arrest in MDA-MB-231. Cell cycle and apoptosis were measured by flow cytometer. Checkpoints of the cell cycle were measured by western blot. In this study, we found that the expression of Cyclin D1 was obviously decreased, while the expression of Chk2 and P21 was increased after PDT treatment. This study showed that MPPa-PDT affected the checkpoints of the cell cycle and led the cells to apoptosis.

  20. Surfactant protein B polymorphisms, pulmonary function and COPD in 10,231 individuals

    DEFF Research Database (Denmark)

    Bækvad-Hansen, M; Nordestgaard, B G; Dahl, Morten

    2011-01-01

    The surfactant protein (SP)-B gene may influence chronic obstructive pulmonary disease (COPD) and, thus, personalised medicine. We tested whether functional polymorphisms in SP-B (rs1130866 (1580T>C), rs2077079 (-18A>C) and rs3024791 (-384G>A)) associate with reduced lung function and risk of COPD...... in the general population. We genotyped 10,231 individuals from the general adult Danish population, and recorded spirometry and hospital admissions due to COPD. Because we previously found an association between the rare SP-B 121ins2 mutation and COPD among smokers, we stratified the analyses for smoking status....... None of the individual SP-B genotypes or genotype combinations were associated with reduced forced expiratory volume in 1 s (FEV1) % predicted, forced vital capacity (FVC) % pred and FEV1/FVC overall or among smokers (p = 0.25-0.99). The odds ratio for spirometrically defined COPD did not differ from 1...

  1. Flexibility damps macromolecular crowding effects on protein folding dynamics: Application to the murine prion protein (121-231)

    Science.gov (United States)

    Bergasa-Caceres, Fernando; Rabitz, Herschel A.

    2014-01-01

    A model of protein folding kinetics is applied to study the combined effects of protein flexibility and macromolecular crowding on protein folding rate and stability. It is found that the increase in stability and folding rate promoted by macromolecular crowding is damped for proteins with highly flexible native structures. The model is applied to the folding dynamics of the murine prion protein (121-231). It is found that the high flexibility of the native isoform of the murine prion protein (121-231) reduces the effects of macromolecular crowding on its folding dynamics. The relevance of these findings for the pathogenic mechanism are discussed.

  2. Transcriptional program induced by factor VIIa-tissue factor, PAR1 and PAR2 in MDA-MB-231 cells

    DEFF Research Database (Denmark)

    Albrektsen, T; Sørensen, B B; Hjortø, G M

    2007-01-01

    -regulated genes was also regulated by a PAR1 agonist peptide suggesting extensive redundancy between FVIIa/PAR2 signaling and thrombin/PAR1 signaling. The FVIIa regulated genes encode cytokines, chemokines and growth factors, and the gene repertoire induced by FVIIa in MDA-MB-231 cells is consistent...... with a role for TF-FVIIa signaling in regulation of a wound healing type of response. Interestingly, a number of genes regulated exclusively by FVIIa/PAR2-mediated cell signaling in MDA-MB-231 cells were regulated by thrombin and a PAR1 agonist, but not by FVIIa, in the TF-expressing glioblastoma U373 cell...

  3. The Relativistic Jet-accretion Flow–Wind Connection in Mrk 231

    Science.gov (United States)

    Reynolds, Cormac; Punsly, Brian; Miniutti, Giovanni; O’Dea, Christopher P.; Hurley-Walker, Natasha

    2017-02-01

    Long-term radio monitoring of the broad absorption line (BAL) quasar Mrk 231 at 17.6 GHz detected a strong flare in 2015. This triggered four epochs of Very Long Baseline Array (VLBA) observations from 8.4 to 43 GHz as well as three epochs of X-ray observations with NuSTAR and two with XMM over a 15 week period. Two ejected components were detected by the VLBA observations. A conservative lower bound on the apparent speed of the first ejection is attained by assuming that it was ejected when the flare began, {v}{app}> 3.15c. Serendipitous far-UV Hubble Space Telescope observations combined with our long-term radio monitoring seem to indicate that episodes of relativistic ejections suppress flux that is emitted at wavelengths shortward of the peak of the far-UV spectral energy distribution, similar to what has been observed in radio-loud quasars. Episodes of strong jet production also seem to suppress the high-ionization BAL wind seen in weak jet states. We found a statistically significant increase (∼ 25 % ) of the 3–12 keV flux during the radio flare relative to a quiescent radio state. This is explained by an ultra-fast (∼0.06c) X-ray-absorbing photoionized wind that is significantly detected only in the low-radio state (similar to Galactic black holes). Mrk 231 is becoming more radio loud. We found that the putative parsec-scale radio lobe doubled in brightness in nine years. Furthermore, large flares are more frequent, with three major flares occurring at ∼2 year intervals.

  4. Androstane derivatives induce apoptotic death in MDA-MB-231 breast cancer cells.

    Science.gov (United States)

    Jakimov, Dimitar S; Kojić, Vesna V; Aleksić, Lidija D; Bogdanović, Gordana M; Ajduković, Jovana J; Djurendić, Evgenija A; Penov Gaši, Katarina M; Sakač, Marija N; Jovanović-Šanta, Suzana S

    2015-11-15

    Biological investigation was conducted to study in vitro antiproliferative and pro-apoptotic potential of selected 17α-picolyl and 17(E)-picolinylidene androstane derivatives. The antiproliferative impact was examined on six human tumor cell lines, including two types of breast (MCF-7 and MDA-MB-231), prostate (PC3), cervical (HeLa), colon (HT 29) and lung cancer (A549), as well as one normal fetal lung fibroblasts cell line (MRC-5). All derivatives selectively decreased proliferation of estrogen receptor negative MDA-MB-231 breast cancer cells after 48 h and 72 h treatment and compounds showed time-dependent activity. We used this cell line to investigate cell cycle modulation and apoptotic cell death induction by flow cytometry, expression of apoptotic proteins by Western blot and apoptotic morphology by visual observation. Tested androstane derivatives affected the cell cycle distribution and induced apoptosis and necrosis. Compounds had different and specific mode of action, depending on derivative type and exposure time. Some compounds induced significant apoptosis measured by Annexin V test compared to reference compound formestane. Higher expression of pro-apoptotic BAX, downregulation of anti-apoptotic Bcl-2 and cleavage of PARP protein were confirmed in almost all treated samples, but the lack of caspase-3 activation suggested the induction of apoptosis in caspase-independent manner. More cells with apoptotic morphology were observed in samples after prolonged treatment. Structure-activity relationship analysis was performed to find correlations between the structure variations of investigated derivatives and observed biological effects. Results of this study showed that some of the investigated androstane derivatives have good biomedical potential and could be candidates for anticancer drug development.

  5. Grape seed extract suppresses MDA-MB231 breast cancer cell migration and invasion.

    Science.gov (United States)

    Dinicola, Simona; Pasqualato, Alessia; Cucina, Alessandra; Coluccia, Pierpaolo; Ferranti, Francesca; Canipari, Rita; Catizone, Angela; Proietti, Sara; D'Anselmi, Fabrizio; Ricci, Giulia; Palombo, Alessandro; Bizzarri, Mariano

    2014-01-01

    Breast cancer remains a leading cause of mortality among women. In metastasis, cascade migration of cancer cells and invasion of extracellular matrix (ECM) represent critical steps. Urokinase-type plasminogen activator (uPA), as well as metalloproteinases MMP-2 and MMP-9, strongly contribute to ECM remodelling, thus becoming associated with tumour migration and invasion. In addition, the high expression of cytoskeletal (CSK) proteins, as fascin, has been correlated with clinically aggressive metastatic tumours, and CSK proteins are thought to affect the migration of cancer cells. Consumption of fruits and vegetables, characterized by high procyanidin content, has been associated to a reduced mortality for breast cancer. Therefore, we investigated the biological effect of grape seed extract (GSE) on the highly metastatic MDA-MB231 breast cancer cell line, focusing on studying GSE ability in inhibiting two main metastatic processes, i.e., cell migration and invasion. After MDA-MB231 breast cancer cells stimulated with GSE migration and invasion were evaluated by means of trans-well assays and uPA as well as MMPs activity was detected by gelatin zymography. Fascin, β-catenin and nuclear factor-κB (NF-κB) expression were determined using western blot technique. β-Catenin localization was observed by confocal microscopy. We observed that high concentrations of GSE inhibited cell proliferation and apoptosis. Conversely, low GSE concentration decreased cell migration and invasion, likely by hampering β-catenin expression and localization, fascin and NF-κB expression, as well as by decreasing the activity of uPA, MMP-2 and MMP-9. These results make GSE a powerful candidate for developing preventive agents against cancer metastasis.

  6. Graded hypoxia modulates the invasive potential of HT1080 fibrosarcoma and MDA MB231 carcinoma cells.

    Science.gov (United States)

    Subarsky, Patrick; Hill, Richard P

    2008-01-01

    Spatial and temporal oxygen heterogeneity exists in most solid tumour microenvironments due to an inadequate vascular network supplying a dense population of tumour cells. An imbalance between oxygen supply and demand leads to hypoxia within a significant proportion of a tumour, which has been correlated to the likelihood of metastatic dissemination in both rodent tumour models and human patients. Experimentally, it has been demonstrated that near-anoxic in vitro exposure results in transiently increased metastatic potential in some tumour cell lines. The purpose of this study was to examine the effect of graded low oxygen conditions on the invasive phenotype of human tumour cells using an in vitro model of basement membrane invasion, in which we measured oxygen availability directly at the invasion surface of the transwell chamber. Our results show a relationship between culture vessel geometry and time to achieve hypoxia which may affect the interpretation of low oxygen experiments. We exposed the human tumour cell lines, HT1080 and MDA MB231, to graded normobaric oxygen (5% O(2)-0.2% O(2)) either during or prior to in vitro basement membrane invasion to simulate conditions of intravasation and extravasation. A secondary aim was to investigate the potential regulation of matrix metalloproteinase activity by oxygen availability. We identified significant reductions in invasive ability under low oxygen conditions for the HT1080 cell line and an increase in invasion at intermediate oxygen conditions for the MDA MB231 cell line. There were differences in the absolute activity of the individual matrix metalloproteinases, MMP-2, -9, -14, between the two cell lines, however there were no significant changes following exposure to hypoxic conditions. This study demonstrates cell line specific effects of graded oxygen levels on invasive potential and suggests that intermediate levels of low oxygen may increase metastatic dissemination.

  7. Application of alternative alkali M-231P to airflow dyeing process%代用碱M-231P在气流染色工艺中的应用

    Institute of Scientific and Technical Information of China (English)

    张天星

    2011-01-01

    代用碱M-231P是由多种碱剂和缓冲剂组成的缓冲体系,介绍了其在活性染料固色中的应用性能.优化应用工艺为:预加纯碱0.8~2.0g/L,电解质用量较传统纯碱工艺增加8%,M-231P用量为纯碱的1/6~1/8.该工艺能达到传统碱固色工艺的得色量和色牢度要求,且节省水和时间.%Substitute alkali M-231P is a buffer system composed of several kinds of alkali and buffer agents.The fixation performance of substitute alkali in airflow dyeing with reactive dyes is introduced, and the process is optimized as follows: preadding 0.8 ~ 2.0 g/L soda, the amount of electrolyte increased by 8% compared with that of conventional alkali method, M231P dosage is 1/6 ~ 1/8 of soda.Color yield and color fastness of the dyeings with substitute alkali are similar to those with conventional process, but the former features low water consumption and shortened processing time.

  8. ADM与5Fu可抑制MDA-MB231乳癌细胞的SNCG表达%ADM and 5Fu inhibit the synuclein-γexpression of MDA-MB231 breast cancer cells

    Institute of Scientific and Technical Information of China (English)

    袁光波; 张幸平; 何金花; 唐卫军; 陈睿

    2008-01-01

    目的 研究乳癌临床常用化疗药物顺铂(ciaplalin or DDP),阿霉素(adriamycin,ADM),氟尿嘧啶(fluorouradl,5Fu)对MDA-MB231乳癌细胞SNCG表达的干扰效应.方法 通过RT-PCR及免疫组织化学法检测上述药物处理组和阴性对照组MDA-MB231细胞的SNCG表达状况,用Quantity One软件及北航真彩色医学图像处理系统(CM-20008)分别对各组SNCG mR-NA和蛋白相对表达水平进行分析.结果 ADM和5Fu处理组与阴性对照组比较,MDA-MB231细胞的SNCG mRNA及蛋白表达水平差异均有统计学意义(P值均小于0.05),而DDP处理组表达水平与对照组无差别.结论 ADM和5Fu可抑制MDA-MB231细胞的SNCG表达.

  9. The Companion to the Central Mira Star of the Protoplanetary Nebula OH 231.8+4.2

    Science.gov (United States)

    Contreras, C. Sanchez; DePaz, A. Gil; Sahai, R.

    2004-01-01

    We present deep optical long-slit spectra of the peculiar protoplanetary nebula (PPN) OH 231.8+4.2 obtained with the 6.5 m Baade Telescope at Las Campanas Observatory (Chile). In addition to the molecular absorption bands characteristic of the M9-10 III star inside OH 231.8+4.2 (QX Pup), we identify lines of the Balmer series in absorption, which do not form in the cool atmospheres of late M-type stars. We also confirm the presence of a blue continuum excess with an intensity that is a factor 30 larger than that expected for an M9-10 III star. Our results indicate the presence of a source hotter than QX Pup illuminating OH 231.8+4.2 that is likely a main-sequence star with spectral type A. We discuss how the formation and nebular evolution of OH 231.8+4.2 could have been affected by the presence of a binary system in its core.

  10. X-231B technology demonstration for in situ treatment of contaminated soil: Contaminant characterization and three dimensional spatial modeling

    Energy Technology Data Exchange (ETDEWEB)

    West, O.R.; Siegrist, R.L.; Mitchell, T.J.; Pickering, D.A.; Muhr, C.A.; Greene, D.W.; Jenkins, R.A.

    1993-11-01

    Fine-textured soils and sediments contaminated by trichloroethylene (TCE) and other chlorinated organics present a serious environmental restoration challenge at US Department of Energy (DOE) sites. DOE and Martin Marietta Energy Systems, Inc. initiated a research and demonstration project at Oak Ridge National Laboratory. The goal of the project was to demonstrate a process for closure and environmental restoration of the X-231B Solid Waste Management Unit at the DOE Portsmouth Gaseous Diffusion Plant. The X-231B Unit was used from 1976 to 1983 as a land disposal site for waste oils and solvents. Silt and clay deposits beneath the unit were contaminated with volatile organic compounds and low levels of radioactive substances. The shallow groundwater was also contaminated, and some contaminants were at levels well above drinking water standards. This document begins with a summary of the subsurface physical and contaminant characteristics obtained from investigative studies conducted at the X-231B Unit prior to January 1992 (Sect. 2). This is then followed by a description of the sample collection and analysis methods used during the baseline sampling conducted in January 1992 (Sect. 3). The results of this sampling event were used to develop spatial models for VOC contaminant distribution within the X-231B Unit.

  11. Potential suppressive effects of gentian violet on human breast cancer MDA-MB-231 cells in vitro: Comparison with gemcitabine.

    Science.gov (United States)

    Yamaguchi, Masayoshi; Murata, Tomiyasu

    2016-08-01

    Gentian violet (GV), a cationic triphenylmethane dye, is used as an antifungal and antibacterial agent. Recently, attention has been focused on GV as a potential chemotherapeutic and antiangiogenic agent. The present study was undertaken to determine the suppressive effects of GV on human breast cancer MDA-MB-231 cells in vitro. The proliferation of MDA-MB-231 cells was suppressed by culture with GV (1-200 nM). The suppressive effects of GV on cell proliferation were not potentiated in the presence of various inhibitors that induce cell cycle arrest in vitro. This finding suggested that GV inhibits G1 and G2/M phase cell cycle arrest in MDA-MB-231 cells. The suppressive effects of GV on proliferation are mediated through the inhibition of various signaling pathways or nuclear transcription in vitro. Moreover, the suppressive effects of GV on cell proliferation were compared with that of gemcitabine, a strong antitumor agent that induces nuclear DNA damage. Notably, the culture with gemcitabine >50 nM suppressed cell proliferation, while the effects of GV were observed at >1 nM. The suppressive effects of gemcitabine on cell proliferation were not potentiated by GV. Overall, the present study demonstrated that GV exhibits a potential suppressive effect on the proliferation of human breast cancer MDA-MB-231 cells in vitro.

  12. Vascular endothelial growth inhibitor affects the invasion, apoptosis and vascularisation in breast cancer cell line MDA-MB-231

    Institute of Scientific and Technical Information of China (English)

    Gao Yinguang; Ge Zhicheng; Zhang Zhongtao; Bai Zhigang; Ma Xuemei; Wang Yu

    2014-01-01

    Background Breast cancer is one of the most common malignant female diseases worldwide.It is a significant threat to every woman's health.Vascular endothelial growth inhibitor (VEGI) is known to be abundant in endothelial cells.According to previous literature,overexpression of VEGI has been shown to inhibit tumor neovascularisation and progression in cellular and animal models,but there has been limited research on the significance of VEGI in the breast cancer.Methods In our study,cell lines MDA-MB-231 were first constructed in which VEGI mediated by lentivirus over-expressed.The effects of VEGI over-expression on MDA-MB-231 cells were investigated both in vitro and in vivo.The expression of VEGI in the MDA-MB-231 cells after infection of lentivirus was analyzed using real-time PCR and Western blotting.The effect of the biological characteristics of MDA-MB-231 cells was assessed by growth,invasion,adhesion,and migration assay with subcutaneous tumor-bearing nude mice models.Then the growth curves of the subcutaneous tumors were studied.Expressions of VEGI,CD31 and CD34 in the tumors were analyzed by immunohistochemistry and apoptosis was detected by flow cytometry and immunohistochemistry.Results Infection of MDA-MB-231 cells within the lentivirus resulted in approximately a 1 000-fold increase in the expression of VEGI.As can be seen in the invasion,adhesion and migration assay,the over-expression of VEGI can inhibit the ability of MDA-MB-231 cells during migration,adhesion and invasion.The volume of the subcutaneous tumor in the over-expression group was distinctly and significantly less than that of the control groups.Immunohistochemistry analysis of the tumor biopsies cleady showed the expression of VEGI in the over-expression group increased while CD31 and CD34 decreased significantly.In vitro and in vivo,the early apoptosis rate and the apoptosis index were increased within the VEGI over-expression group as compared with the control group.Conclusions Taken

  13. Nustar Reveals an Intrinsically X-ray Weak Broad Absorption Line Quasar in the Ultraluminous Infrared Galaxy Markarian 231

    Science.gov (United States)

    Teng, Stacy H.; Brandt. W. N.; Harrison, F. A.; Luo, B.; Alexander, D. M.; Bauer, F. E.; Boggs, S. E.; Christensen, F. E.; Comastri, A.; Craig, W. W.; Fabian, A. C.; Farrah, D.; Fiore, F.; Gandhi, P.; Grefenstette, B. W.; Hailey, C. J.; Hickox, R. C.; Madsen, K. K.; Ptak, A. F.; Rigby, Jane Rebecca; Risaliti, G.; Saz, C.; Stern, D.; Veilleux, S.; Walton, D. J.; Wik, D. R.; Zhang, W. W.

    2014-01-01

    We present high-energy (3-30 keV) NuSTAR observations of the nearest quasar, the ultraluminous infrared galaxy (ULIRG) Markarian 231 (Mrk 231), supplemented with new and simultaneous low-energy (0.5-8 keV) data from Chandra. The source was detected, though at much fainter levels than previously reported, likely due to contamination in the large apertures of previous non-focusing hard X-ray telescopes. The full band (0.5-30 keV) X-ray spectrum suggests the active galactic nucleus (AGN) in Mrk 231 is absorbed by a patchy and Compton-thin N(sub H) approx. 1.2(sup +0.3) sub-0.3) x 10(exp 23) / sq cm) column. The intrinsic X-ray luminosity L(sub 0.5-30 Kev) approx. 1.0 x 10(exp 43) erg /s) is extremely weak relative to the bolometric luminosity where the 2-10 keV to bolometric luminosity ratio is approx. 0.03% compared to the typical values of 2-15%. Additionally, Mrk 231 has a low X-ray-to-optical power law slope alpha(sub 0X) approx. -1.7. It is a local example of a low-ionization broad absorption line (LoBAL) quasar that is intrinsically X-ray weak. The weak ionizing continuum may explain the lack of mid-infrared [O IV], [Ne V], and [Ne VI] fine-structure emission lines which are present in sources with otherwise similar AGN properties. We argue that the intrinsic X-ray weakness may be a result of the super-Eddington accretion occurring in the nucleus of this ULIRG, and may also be naturally related to the powerful wind event seen in Mrk 231, a merger remnant escaping from its dusty cocoon.

  14. Anticancer property of sediment actinomycetes against MCF-7 and MDA-MB-231 cell lines

    Institute of Scientific and Technical Information of China (English)

    Ravikumar S; Fredimoses M; Gnanadesigan M

    2012-01-01

    Objective: To investigate the anticancer property of marine sediment actinomycetes against two different breast cancer cell lines. Methods:In vitro anticancer activity was carried out against breast (MCF-7 and MDA-MB-231) cancer cell lines. Partial sequences of the 16s rRNA gene, phylogenetic tree construction, multiple sequence analysis and secondary structure analysis were also carried out with the actinomycetes isolates. Results: Of the selected five actinomycete isolates, ACT01 and ACT02 showed the IC50 value with (10.13±0.92) and (22.34±5.82)μg/mL concentrations, respectively for MCF-7 cell line at 48 h, but ACT01 showed the minimum (18.54±2.49 μg/mL) level of IC50 value with MDA-MB-231 cell line. Further, the 16s rRNA partial sequences of ACT01, ACT02, ACT03, ACT04 and ACT05 isolates were also deposited in NCBI data bank with the accession numbers of GQ478246, GQ478247, GQ478248, GQ478249 and GQ478250, respectively. The phylogenetic tree analysis showed that, the isolates of ACT02 and ACT03 were represented in group I and III, respectively, but ACT01 and ACT02 were represented in group II. The multiple sequence alignment of the actinomycete isolates showed that, the maximum identical conserved regions were identified with the nucleotide regions of 125 to 221st base pairs, 65 to 119th base pairs and 55, 48 and 31st base pairs. Secondary structure prediction of the 16s rRNA showed that, the maximum free energy was consumed with ACT03 isolate (-45.4 kkal/mol) and the minimum free energy was consumed with ACT04 isolate (-57.6 kkal/mol). Conclusions:The actinomycete isolates of ACT01 and ACT02 (GQ478246 and GQ478247) which are isolated from sediment sample can be further used as anticancer agents against breast cancer cell lines.

  15. Protactinium-231 as a new fissionable material for nuclear reactors that can produce nuclear fuel with stable neutron-multiplying properties

    Energy Technology Data Exchange (ETDEWEB)

    Shmelev, Anatoly N.; Kulikov, Gennady G.; Kulikov, Evgeny G.; Apse, Vladimir A. [National Research Nuclear Univ. MEPHI, Moscow (Russian Federation). Moscow Engineering Physics Inst.

    2016-03-15

    Main purpose of the study is justifying doping of protactinium-231 into fuel compositions of advanced nuclear reactors with the ultimate aim to improve their operation safety and economic efficiency. Protactinium-231 could be generated in thorium blankets of hybrid thermonuclear facilities. The following results were obtained: 1. Protactinium-231 has some favorable features for its doping into nuclear fuel; 2. Protactinium containing fuel compositions can be characterized by the higher values of fuel burn-up, the longer values of fuel lifetime and the better proliferation resistance; 3. as protactinium-231 is the stronger neutron absorber than uranium-238, remarkably lower amounts of protactinium-231 may be doped into fuel compositions. The free space could be occupied by materials which are able to improve heat conductivity and refractoriness of fuel. As a consequence, operation safety of nuclear reactors could be upgraded.

  16. Stable transfection of estrogen receptor-alpha suppresses expression of cyclooxygenase-2 and vascular endothelial growth factor-C in MDA-MB-231 breast cancer cells

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hui; LIN Ying; XIAO Ying; WANG San-ming; LIU Xiang-xia; WANG Shen-ming

    2010-01-01

    Background Estrogen receptor (ER)-negative breast cancer cells are more aggressive than ER-positive cells. Elevated levels of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor-C (VEGF-C) expression have been detected in cultured human breast cancer cells and are associated with negative hormone receptor status. In this study, we created ERα stable transfectants in MDA-MB-231 cells to explore the effect of ERα on cell growth and COX-2 and VEGF-C expression.Methods The green fluorescent protein (GFP)-ERα plasmids were stably transfected into ER-negative MDA-MB-231 cells. The proliferation and migration of untransfected MDA-MB-231 cells, ERα-transfected MDA-MB-231 cells and ER-positive MCF-7 cells were determined. The expression of COX-2, and the levels of VEGF-C mRNA and the VEGF-C secretion concentration were assayed in these cell lines.Results The proliferation and migration capacities of ERα-tranfected MDA-MB-231 cells were significantly decreased (P <0.05). The expression of COX-2 was significantly lower in ERa-tranfected MDA-MB-231 cells than in untranfected MDA-MB-231 cells. The mRNA and protein levels of VEGF-C were lower in ERa-tranfected MDA-MB-231 cells than in untransfected MDA-MB-231 cells (P<0.05).Conclusions ERα stable transfection inhibits proliferation and migration capacities of MDA-MB-231 cells and decreases expression of COX-2 and VEGF-C. The decreases of proliferation and migration capacities may be related to suppression of COX-2 and VEGF-C expression.

  17. Optimized Method for Untargeted Metabolomics Analysis of MDA-MB-231 Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Amanda L. Peterson

    2016-09-01

    Full Text Available Cancer cells often have dysregulated metabolism, which is largely characterized by the Warburg effect—an increase in glycolytic activity at the expense of oxidative phosphorylation—and increased glutamine utilization. Modern metabolomics tools offer an efficient means to investigate metabolism in cancer cells. Currently, a number of protocols have been described for harvesting adherent cells for metabolomics analysis, but the techniques vary greatly and they lack specificity to particular cancer cell lines with diverse metabolic and structural features. Here we present an optimized method for untargeted metabolomics characterization of MDA-MB-231 triple negative breast cancer cells, which are commonly used to study metastatic breast cancer. We found that an approach that extracted all metabolites in a single step within the culture dish optimally detected both polar and non-polar metabolite classes with higher relative abundance than methods that involved removal of cells from the dish. We show that this method is highly suited to diverse applications, including the characterization of central metabolic flux by stable isotope labelling and differential analysis of cells subjected to specific pharmacological interventions.

  18. Evidence for AGN Feedback in the Broad Absorption Lines and Reddening of Mrk 231

    CERN Document Server

    Leighly, Karen M; Baron, Eddie; Lucy, Adrian B; Dietrich, Matthias; Gallagher, Sarah C

    2014-01-01

    We present the first J-band spectrum of Mrk 231, which reveals a large \\ion{He}{1}*$\\lambda 10830$ broad absorption line with a profile similar to that of the well-known \\ion{Na}{1} broad absorption line. Combining this spectrum with optical and UV spectra from the literature, we show that the unusual reddening noted by \\citet{veilleux13} is explained by a reddening curve like those previously used to explain low values of total-to-selective extinction in SNe Ia. The nuclear starburst may be the origin and location of the dust. Spatially-resolved emission in the broad absorption line trough suggests nearly full coverage of the continuum emission region. The broad absorption lines reveal higher velocities in the \\ion{He}{1}* lines (produced in the quasar-photoionized \\ion{H}{2} region) compared with the \\ion{Na}{1} and \\ion{Ca}{2} lines (produced in the corresponding partially-ionized zone). {\\it Cloudy} simulations show that a density increase is required between the \\ion{H}{2} and partially-ionized zones to ...

  19. A probable Milli-Parsec Supermassive Binary Black Hole in the Nearest Quasar Mrk 231

    CERN Document Server

    Yan, Chang-Shuo; Dai, Xinyu; Yu, Qingjuan

    2015-01-01

    Supermassive binary black holes (BBHs) are unavoidable products of galaxy mergers and are expected to exist in the cores of many quasars. Great effort has been made during the past several decades to search for BBHs among quasars; however, observational evidence for BBHs remains elusive and ambiguous, which is difficult to reconcile with theoretical expectations. In this paper, we show that the distinct optical-to-UV spectrum of Mrk 231 can be well interpreted as emission from accretion flows onto a BBH, with a semimajor axis of ~590AU and an orbital period of ~1.2 year. The flat optical and UV continua are mainly emitted from a circumbinary disk and a mini-disk around the secondary black hole (BH), respectively; and the observed sharp drop off and flux deficit at wavelength lambda ~ 4000-2500 Angstrom is due to a gap (or hole) opened by the secondary BH migrating within the circumbinary disk. If confirmed by future observations, this BBH will provide a unique laboratory to study the interplay between BBHs an...

  20. Infrared polarimetry of Mrk 231: Scattering off hot dust grains in the central core

    CERN Document Server

    Lopez-Rodriguez, E; Jones, T J; Siebenmorgen, R; Roche, P F; Levenson, N A; Alonso-Herrero, A; Perlman, E; Ichikawa, K; Almeida, C Ramos; Gonzalez-Martin, O; Nikutta, R; Martinez-Paredes, M; Shenoy, D; Gordon, M S; Telesco, C M

    2016-01-01

    We present high-angular (0.17$-$0.35 arcsec) resolution imaging polarimetric observations of Mrk 231 in the 3.1 $\\mu$m filter using MMT-Pol on the 6.5-m MMT, and in the 8.7 $\\mu$m, 10.3 $\\mu$m, and 11.6 $\\mu$m filters using CanariCam on the 10.4-m Gran Telescopio CANARIAS. In combination with already published observations, we compile the 1$-$12 $\\mu$m total and polarized nuclear spectral energy distribution (SED). The total flux SED in the central 400 pc is explained as the combination of 1) a hot (731 $\\pm$ 4 K) dusty structure, directly irradiated by the central engine, which is at 1.6 $\\pm$ 0.1 pc away and attributed to be in the pc-scale polar region, 2) an optically-thick, smooth and disk-like dusty structure (`torus') with an inclination of 48 $\\pm$ 23$^{\\circ}$ surrounding the central engine, and 3) an extinguished (A$_{\\mbox{V}} =$ 36 $\\pm$ 5 mag) starburst component. The polarized SED decreases from 0.77 $\\pm$ 0.14 per cent at 1.2 $\\mu$m to 0.31 $\\pm$ 0.15 per cent at 11.6 $\\mu$m and follows a power...

  1. Herschel PACS Spectroscopic Diagnostics of Local ULIRGs: Conditions and Kinematics in Mrk 231

    CERN Document Server

    Fischer, Jacqueline; González-Alfonso, Eduardo; Graciá-Carpio, Javier; Hailey-Dunsheath, Steve; Poglitsch, Albrecht; Contursi, Alessandra; Lutz, Dieter; Genzel, Reinhard; Sternberg, Amiel; Verma, Aprajita; Tacconi, Linda

    2010-01-01

    In this first paper on the results of our Herschel PACS survey of local Ultraluminous Infrared Galaxies (ULIRGs), as part of our SHINING survey of local galaxies, we present far-infrared spectroscopy of Mrk 231, the most luminous of the local ULIRGs, and a type 1 broad absorption line AGN. For the first time in a ULIRG, all observed far-infrared fine-structure lines in the PACS range were detected and all were found to be deficient relative to the far infrared luminosity by 1 - 2 orders of magnitude compared with lower luminosity galaxies. The deficits are similar to those for the mid-infrared lines, with the most deficient lines showing high ionization potentials. Aged starbursts may account for part of the deficits, but partial covering of the highest excitation AGN powered regions may explain the remaining line deficits. A massive molecular outflow, discovered in OH and 18OH, showing outflow velocities out to at least 1400 km/sec, is a unique signature of the clearing out of the molecular disk that formed ...

  2. Meridional circulation across the Antarctic Circumpolar Current serves as a double 231Pa and 230Th trap

    Science.gov (United States)

    Rutgers van der Loeff, Michiel; Venchiarutti, Celia; Stimac, Ingrid; van Ooijen, Jan; Huhn, Oliver; Rohardt, Gerd; Strass, Volker

    2016-12-01

    Upwelling of Circumpolar Deep Water in the Weddell Gyre and low scavenging rates south of the Antarctic Circumpolar Current (ACC) cause an accumulation of particle reactive nuclides in the Weddell Gyre. A ventilation/reversible scavenging model that successfully described the accumulation of 230Th in this area was tested with other particle reactive nuclides and failed to adequately describe the depth-distributions of 231Pa and 210Pb. We present here a modified model that includes a nutrient-like accumulation south of the Antarctic Polar Front in an upper meridional circulation cell, as well as transport to a deep circulation cell in the Weddell Gyre by scavenging and subsequent release at depth. The model also explains depletion of 231Pa and 230Th in Weddell Sea Bottom Water (WSBW) by ventilation of newly formed deep water on a timescale of 10 years, but this water mass is too dense to leave the Weddell Gyre. In order to quantify the processes responsible for the 231Pa- and 230Th-composition of newly formed Antarctic Bottom Water (AABW) we present a mass balance of 231Pa and 230Th in the Atlantic sector of the Southern Ocean based on new data from the GEOTRACES program. The ACC receives 6.0 ± 1.5 ×106 dpms-1 of 230Th from the Weddell Sea, similar in magnitude to the net input of 4.2 ± 3.0 ×106 dpms-1 from the north. For 231Pa, the relative contribution from the Weddell Sea is much smaller, only 0.3 ± 0.1 ×106, compared to 2.7 ± 1.4 ×106 dpms-1 from the north. Weddell Sea Deep Water (WSDW) leaving the Weddell Gyre northward to form AABW is exposed in the ACC to resuspended opal-rich sediments that act as efficient scavengers with a Th/Pa fractionation factor F ≤ 1. Hydrothermal inputs may provide additional removal with low F. Scavenging in the full meridional circulation across the opal-rich ACC thus acts as a double 231Pa and 230Th trap that preconditions newly formed AABW.

  3. Combination of cisplatin and bromelain exerts synergistic cytotoxic effects against breast cancer cell line MDA-MB-231 in vitro.

    Science.gov (United States)

    Pauzi, Ahmad Zaim Mat; Yeap, Swee Keong; Abu, Nadiah; Lim, Kian Lam; Omar, Abdul Rahman; Aziz, Suraini Abdul; Chow, Adam Leow Thean; Subramani, Tamilselvan; Tan, Soon Guan; Alitheen, Noorjahan Banu

    2016-01-01

    Bromelain, which is a cysteine endopeptidase commonly found in pineapple stems, has been investigated as a potential anti-cancer agent for the treatment of breast cancer. However, information pertaining to the effects of combining bromelain with existing chemotherapeutic drugs remains scarce. This study aimed to investigate the possible synergistic cytotoxic effects of using bromelain in combination with cisplatin on MDA-MB-231 human breast cancer cells. MDA-MB-231 cells were treated with different concentrations (0.24-9.5 µM) of bromelain or cisplatin alone, as well as four different combinations of these two agents to assess their individual and combination effects after 24 and 48 h. Cell viability was analyzed using an MTT assay. The induction of apoptosis was assessed using cell cycle analysis and an Annexin V-FITC assay. The role of the mitochondrial membrane potential in the apoptotic process was assessed using a JC-1 staining assay. Apoptotic protein levels were assessed by western blot analysis and proteome profiling using an antibody array kit. Single-agent treatment with cisplatin or bromelain led to dose- and time-dependent decreases in the viability of the MDA-MB-231 cells at 24 and 48 h. Furthermore, most of the combinations evaluated in this study displayed synergistic effects against MDA-MB-231 cells at 48 h, with combination 1 (bromelain 2 µM + cisplatin 1.5 µM) exhibiting the greatest synergistic effect (P = 0.000). The results of subsequent assays indicated that combination 1 treatment induced apoptosis via mitochondria-mediated pathway. Combination 1 also resulted in significant decreases in the levels of several apoptotic proteins such as Bcl-x and HSP70, compared with bromelain (P = 0.002 and 0.000, respectively) or cisplatin (P = 0.000 and 0.001, respectively) single treatment. Notably, MDA-MB-231 cells treated with combination 1 showed increased levels of the pro-apoptotic proteins Bax compared with those treated with

  4. Dillenia suffruticosa dichloromethane root extract induced apoptosis towards MDA-MB-231 triple-negative breast cancer cells.

    Science.gov (United States)

    Foo, Jhi Biau; Saiful Yazan, Latifah; Tor, Yin Sim; Wibowo, Agustono; Ismail, Norsharina; Armania, Nurdin; Cheah, Yoke Kqueen; Abdullah, Rasedee

    2016-07-01

    Dillenia suffruticosa is traditionally used for treatment of cancerous growth including breast cancer in Malaysia. Dillenia suffruticosa is a well-known medicinal plant in Malaysia for the treatment of cancer. Nevertheless, no study has been reported the cytotoxicity of this plant towards MDA-MB-231 triple-negative breast cancer cells. The present study was designed to investigate the mode of cell death and signalling pathways of MDA-MB-231 cells treated with dichloromethane Dillenia suffruticosa root extract (DCM-DS). Extraction of Dillenia suffruticosa root was performed by the use of sequential solvent procedure. The cytotoxicity of DCM-DS was determined by using MTT assay. The mode of cell death was evaluated by using an inverted light microscope and flow cytometry analysis using Annexin-V/PI. Cell cycle analysis and measurement of reactive oxygen species level were performed by using flow cytometry. The cells were treated with DCM-DS and antioxidants α-tocopherol or ascorbic acid to evaluate the involvement of ROS in the cytotoxicity of DCM-DS. Effect of DCM-DS on the expression of antioxidant, apoptotic, growth, survival genes and proteins were analysed by using GeXP-based multiplex system and Western blot, respectively. The cytotoxicity of compounds isolated from DCM-DS was evaluated towards MDA-MB-231 cells using MTT assay. DCM-DS induced apoptosis, G2/M phase cell cycle arrest and oxidative stress in MDA-MB-231 cells. The induction of apoptosis in MDA-MB-231 cells by DCM-DS is possibly due to the activation of pro-apoptotic JNK1 and down-regulation of anti-apoptotic ERK1, which in turn down-regulates anti-apoptotic BCL-2 to increase the BAX/BCL-2 ratio to initiate the mitochondrial apoptotic pathway. The cell cycle arrest in DCM-DS-treated MDA-MB-231 cells is possibly via p53-independent but p21-dependent pathway. A total of 3 triterpene compounds were isolated from DCM-DS. Betulinic acid appears to be the most major and most cytotoxic compound in DCM

  5. 改造DTL-231调节器为一个新型的抗喘振调节器%To Remould DTL-231 Regulator into a Surge-Resistant Regulator

    Institute of Scientific and Technical Information of China (English)

    任秀珍

    1987-01-01

    当泵或压缩机的工作状态大范围变化时,由于喘振缘故,会产生一种奇特的不稳定现象,这种现象可能破坏生产过程的连续条件.泵或压缩机的压力与(或)流量抗喘振控制系统,可以用改型DTL-231调节器来实现,这种改型的调节器具有两种特殊的组合功能,即选择性调节与抗积分饱和.本文详细介绍改型DTL-231调节器的结构和应用.

  6. PEA3 activates CXCR4 transcription in MDA-MB-231 and MCF7 breast cancer cells

    Institute of Scientific and Technical Information of China (English)

    Shengmei Gu; Li Chen; Qi Hong; Tingting Yan; Zhigang Zhuang; Qiaoqiao wang; Wei Jin; Hua Zhu; Jiong Wu

    2011-01-01

    CXC chemokine receptor 4 (CXCR4) is a cell surface receptor that has been shown to mediate the metastasis of many solid tumors including lung,breast,kidney,and prostate tumors.In this study,we found that overexpression of ets variant gene 4 (PEA3) could elevate CXCR4 mRNA level and CXCR4 promoter activity in human MDA-MB-231 and MCF-7 breast cancer cells.PEA3 promoted CXCR4 expression and breast cancer metastasis.Chromatin immunoprecipitation assay demonstrated that PEA3 could bind to the CXCR4 promoter in the cells transfected with PEA3 expression vector.PEA3 siRNA attenuated CXCR4 promoter activity and the binding of PEA3 to the CXCR4 promoter in MDA-MB-231 and MCF-7 cells.These results indicated that PEA3 could activate CXCR4 promoter transcription and promote breast cancer metastasis.

  7. Inhibitory effects of ginseng sapogenins on the proliferation of triple negative breast cancer MDA-MB-231 cells.

    Science.gov (United States)

    Kwak, Jin Ho; Park, Jun Yeon; Lee, Dahae; Kwak, Jae Young; Park, Eun Hwa; Kim, Ki Hyun; Park, Hye-Jin; Kim, Hyun Young; Jang, Hyuk Jai; Ham, Jungyeob; Hwang, Gwi Seo; Yamabe, Noriko; Kang, Ki Sung

    2014-12-01

    Because of poor prognosis, clinical treatment of triple-negative (TN) breast cancer remains the most challenging factor in cancer treatment. Extensive research into alternative cancer therapies includes studying the naturopathic effects of the medicinal herb ginseng. This study investigates the anti-neoplastic properties of ginseng sapogenins and the derivatives: (1) (20(S)-protopanaxadiol (PPD), (2) 20(S)-protopanaxatriol), (3) (20(S)-dihydroprotopanaxadiol, and (4) 20(S)-dihydroprotopanaxatriol). These compounds were found to prevent the proliferation of MDA-MB-231 human breast cancer cells. PPD was the most potent inhibitor, exhibiting an IC₅₀ (5.87 μM) comparable to that of the chemotherapeutic drug taxol. Furthermore, PPD induced dose-dependent cleavage of caspase-8, caspase-3, and PARP in MDA-MB-231 cells. Thus, we propose that PPD acts as anti-cancer agent by stimulating caspase-dependent apoptosis in breast cancer cells.

  8. Another piece of the puzzle: The fast H I outflow in Mrk 231

    Science.gov (United States)

    Morganti, Raffaella; Veilleux, Sylvain; Oosterloo, Tom; Teng, Stacy H.; Rupke, David

    2016-09-01

    We present the detection, performed with the Westerbork Synthesis Radio Telescope (WSRT) and the Karl Jansky Very Large Array (VLA), of a fast H I 21 cm outflow in the ultra-luminous infrared galaxy Mrk 231. The outflow is observed as shallow H I absorption blueshifted ~1300 km s-1 with respect to the systemic velocity and located against the inner kpc of the radio source. The outflowing gas has an estimated column density between 5 and 15 × 1018Tspin cm-2. We derive the Tspin to lie in the range 400-2000 K and the corresponding H I densities are nHI ~ 10-100 cm-3. Our results complement previous findings and confirm the multiphase nature of the outflow in Mrk 231. Although effects of the interaction between the radio plasma and the surrounding medium cannot be ruled out, the energetics and the lack of a clear kpc-scale jet suggest that the most likely origin of the H I outflow is a wide-angle nuclear wind, as earlier proposed to explain the neutral outflow traced by Na I and molecular gas in this source. Our results suggest that an H I component is present in fast outflows regardless of the acceleration mechanism (wind vs. jet driven) and that it must be connected with common properties of the pre-interaction gas involved. Considering the observed similarity of their column densities, the H I outflow likely represents the inner part of the broad wind identified on larger scales in atomic Na I. The mass outflow rate of the H I outflow (between 8 and 18 M⊙ yr-1) does not appear to be as large as that observed in molecular gas, partly owing to the smaller sizes of the outflowing region sampled by the H I absorption. These characteristics are commonly seen in other cases of outflows driven by the active galactic nucleus (AGN) suggesting that the H I may represent a short intermediate phase in the rapid cooling of the gas. The results further confirm H I as a good tracer for AGN-driven outflows not only in powerful radio sources. We also obtained deeper continuum

  9. Overexpression of the dynein light chain km23-1 in human ovarian carcinoma cells inhibits tumor formation in vivo and causes mitotic delay at prometaphase/metaphase.

    Science.gov (United States)

    Pulipati, Nageswara R; Jin, Qunyan; Liu, Xin; Sun, Baodong; Pandey, Manoj K; Huber, Jonathan P; Ding, Wei; Mulder, Kathleen M

    2011-08-01

    km23-1 is a dynein light chain that was identified as a TGFβ receptor-interacting protein. To investigate whether km23-1 controls human ovarian carcinoma cell (HOCC) growth, we established a tet-off inducible expression system in SKOV-3 cells in which the expression of km23-1 is induced upon doxycycline removal. We found that forced expression of km23-1 inhibited both anchorage-dependent and anchorage-independent growth of SKOV-3 cells. More importantly, induction of km23-1 expression substantially reduced the tumorigenicity of SKOV-3 cells in a xenograft model in vivo. Fluorescence-activated cell sorting analysis of SKOV-3 and IGROV-1 HOCCs demonstrated that the cells were accumulating at G2/M. Phospho-MEK, phospho-ERK and cyclin B1 were elevated, as was the mitotic index, suggesting that km23-1 suppresses HOCCs growth by inducing a mitotic delay. Immunofluorescence analyses demonstrated that the cells were accumulating at prometaphase/metaphase with increases in multipolar and multinucleated cells. Further, although the mitotic spindle assembly checkpoint protein BubR1 was present at the prometaphase kinetochore in Dox+/- cells, it was inappropriately retained at the metaphase kinetochore in Dox- cells. Thus, the mechanism by which high levels of km23-1 suppress ovarian carcinoma growth in vitro and inhibit ovary tumor formation in vivo appears to involve a BubR1-related mitotic delay.

  10. Inhibitory effect of emodin on migration, invasion and metastasis of human breast cancer MDA-MB-231 cells in vitro and in vivo.

    Science.gov (United States)

    Sun, Yang; Wang, Xiufeng; Zhou, Qianmei; Lu, Yiyu; Zhang, Hui; Chen, Qilong; Zhao, Ming; Su, Shibing

    2015-01-01

    In breast cancer, metastasis is the main reason for patient mortality. In the present study, we used breast cancer MDA-MB-231 cells and a mouse xenograft model to demonstrate the effect of emodin on the migration, invasion and metastasis of human breast cancer MDA-MB-231 cells and the related mechanisms. In vitro, wound healing and Transwell assays showed that emodin dose-dependently inhibited the migration and invasion of MDA-MB-231 cells. Enzyme-linked immunosorbent assay (ELISA) showed that emodin decreased the secretion of MMP-2 and MMP-9. Western blot analysis showed that emodin downregulated the expression levels of MMP-2, MMP-9, uPA and uPAR as well as p38 inhibitor SB203580 and ERK inhibitor PD980559, even though TIMP-1 and TIMP-2 were not obviously changed in the MDA-MB-231 cells. Furthermore, emodin inhibited the activity of p38 and ERK1/2 in the MDA-MB-231 cells. In vivo, emodin inhibited lung metastasis in mice bearing the breast cancer MDA-MB-231 xenografts with no obvious changes in body weight, liver and kidney functions. These results indicated that emodin inhibited the lung metastasis of human breast cancer in a mouse xenograft model, and inhibited the invasion of MDA-MB-231 cells associated with the downregulation of MMP-2, MMP-9, uPA and uPAR expression as well as decreased activity of p38 and ERK.

  11. Segregation analysis of 231 Ashkenazi Jewish families for evidence of additional breast cancer susceptibility genes.

    Science.gov (United States)

    Kaufman, David J; Beaty, Terri H; Struewing, Jeffery P

    2003-10-01

    Between 5 and 10% of breast cancer is attributable to inherited cancer susceptibility genes. Mutations in the genes BRCA1 and BRCA2 account for two-thirds of hereditary breast cancer cases. Using segregation analysis, families of cases without BRCA1/2 mutations were studied for statistical evidence of another major breast cancer gene in a community-based sample of Jewish probands tested previously for the presence of three BRCA founder mutations. A total of 231 probands with breast cancer, who do not carry a founder mutation, reported complete data on 602 female first-degree relatives of probands over age 20; 78 of these relatives had breast cancer. Segregation analysis was used to evaluate the likelihood of various genetic and nongenetic models. Sporadic, environmental, and general Mendelian genetic models fit the family data poorly and were rejected. A Mendelian recessive model fit better than dominant and codominant models, although none of these could be rejected. Cumulative incidence curves predicted by the recessive and codominant models fit observed incidence among first-degree relatives well. The assumption of Mendelian transmission of a major recessive gene(s) is compatible with the data. The recessive model predicts that 4% of women would carry the high-risk genotype, with 85% of them developing breast cancer by age 70. There was significant heterogeneity between these families and the 114 BRCA1/2 mutation-positive families from the same study population, implying that this apparent recessive effect is not because of undetected BRCA1/2 mutations. The study adds support for a major autosomal recessive component to breast cancer susceptibility.

  12. Infrared polarimetry of Mrk 231: scattering off hot dust grains in the central core

    Science.gov (United States)

    Lopez-Rodriguez, E.; Packham, C.; Jones, T. J.; Siebenmorgen, R.; Roche, P. F.; Levenson, N. A.; Alonso-Herrero, A.; Perlman, E.; Ichikawa, K.; Ramos Almeida, C.; González-Martín, O.; Nikutta, R.; Martinez-Paredez, M.; Shenoy, D.; Gordon, M. S.; Telesco, C. M.

    2017-01-01

    We present high-angular (0.17-0.35 arcsec) resolution imaging polarimetric observations of Mrk 231 in the 3.1 μm filter using MMT-Pol on the 6.5-m MMT, and in the 8.7, 10.3, and 11.6 μm filters using CanariCam on the 10.4-m Gran Telescopio CANARIAS. In combination with already published observations, we compile the 1-12 μm total and polarized nuclear spectral energy distribution (SED). The total flux SED in the central 400 pc is explained as the combination of (1) a hot (731 ± 4 K) dusty structure, directly irradiated by the central engine, which is at 1.6 ± 0.1 pc away and attributed to be in the pc-scale polar region, (2) an optically-thick, smooth and disc-like dusty structure (`torus') with an inclination of 48° ± 23° surrounding the central engine, and (3) an extinguished (AV = 36 ± 5 mag) starburst component. The polarized SED decreases from 0.77 ± 0.14 per cent at 1.2 μm to 0.31 ± 0.15 per cent at 11.6 μm and follows a power-law function, λ˜0.57. The polarization angle remains constant (˜108°) in the 1-12 μm wavelength range. The dominant polarization mechanism is explained as scattering-off hot dust grains in the pc-scale polar regions.

  13. Regulation of MDA-MB-231 cell proliferation by GSK-3β involves epigenetic modifications under high glucose conditions

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, Chanchal; Kaur, Jasmine; Tikoo, Kulbhushan, E-mail: tikoo.k@gmail.com

    2014-05-15

    Hyperglycemia is a critical risk factor for development and progression of breast cancer. We have recently reported that high glucose induces phosphorylation of histone H3 at Ser 10 as well as de-phosphorylation of GSK-3β at Ser 9 in MDA-MB-231 cells. Here, we elucidate the mechanism underlying hyperglycemia-induced proliferation in MDA-MB-231 breast cancer cells. We provide evidence that hyperglycemia led to increased DNA methylation and DNMT1 expression in MDA-MB-231 cells. High glucose condition led to significant increase in the expression of PCNA, cyclin D1 and decrease in the expression of PTPN 12, p21 and PTEN. It also induced hypermethylation of DNA at the promoter region of PTPN 12, whereas hypomethylation at Vimentin and Snail. Silencing of GSK-3β by siRNA prevented histone H3 phosphorylation and reduced DNMT1 expression. We show that chromatin obtained after immunoprecipitation with phospho-histone H3 was hypermethylated under high glucose condition, which indicates a cross-talk between DNA methylation and histone H3 phosphorylation. ChIP-qPCR analysis revealed up-regulation of DNMT1 and metastatic genes viz. Vimentin, Snail and MMP-7 by phospho-histone H3, which were down-regulated upon GSK-3β silencing. To the best of our knowledge, this is the first report which shows that interplay between GSK-3β activation, histone H3 phosphorylation and DNA methylation directs proliferation of breast cancer cells. - Highlights: • High glucose induces phosphorylation of histone H3 and dephosphorylation of GSK-3β. • Moreover, hyperglycemia also leads to increased DNA methylation in MDA-MB-231 cells. • Inhibition of GSK-3β prevented histone H3 phosphorylation and reduced DNMT1 levels. • Interplay exists between GSK-3β, histone H3 phosphorylation and DNA methylation.

  14. Roscovitine regulates invasive breast cancer cell (MDA-MB231) proliferation and survival through cell cycle regulatory protein cdk5.

    Science.gov (United States)

    Goodyear, Shaun; Sharma, Mahesh C

    2007-02-01

    Roscovitine, a purine analogue, has been considered for the treatment of cancer. Anti-cancer therapeutic efficacy is being evaluated in clinical trials. However, the mechanisms remain unclear. In the present study, cyclic-dependent kinase 5 (cdk5) proved to be a molecular target for roscovitine-triggered apoptosis for highly invasive breast cancer cell death. Because our previous studies have shown a potential role of cdk5 in endothelial cell proliferation/apoptosis [Sharma, M.R., Tuszynski, G.P., Sharma, M.C. (2004). Angiostatin-induced inhibition of endothelial cell proliferation/apoptosis is associated with the down-regulation of cell cycle regulatory protein cdk5. J. Cell Biochem. 91, 398-409], here we not only demonstrate first that Cdk5, p35, and p25 proteins were all expressed in invasive breast cancer cells MDA-MB231 but also showed that cdk5 expression regulates MDA-MB231 cell proliferation. In addition, potent mitogen bFGF up-regulates cdk5 expression. Roscovitine specifically inhibits cdk5 expression/activity in a dose-dependent manner with concomitant inhibition of MDA-MB231 cell proliferation and induction of apoptosis. By contrast, the roscovitine analog olomoucine, a specific inhibitor of cdk4, failed to affect MDA-MB231 cell proliferation and apoptosis which implies the specific involvement of cdk5 in roscovitine-triggered cell death/proliferation. Additionally, roscovitine-mediated inhibition of proliferation is irreversible. These data suggest that cdk5 may have a significant role in the regulation of breast cancer cell proliferation and apoptosis and extend beyond its role in neurogenesis. These results suggest that Cdk5 is a novel player in roscovitine-triggered breast cancer cell apoptosis and inhibition of proliferation, therefore, may be a potential therapeutic target.

  15. Substantial reduction of the gastric carcinoma critical region at 6q16.3-q23.1

    NARCIS (Netherlands)

    Carvalho, B; Seruca, R; Carneiro, F; Buys, CHCM; Kok, K

    Deletions of the long arm of chromosome 6 are a common event in gastric carcinomas. In a previous study, deletion mapping of 6q identified two smallest regions of overlap (SROs) of heterozygous deletions: one interstitial, spanning 12-16 cM, bordered by D6S268 (6q16.3-q21) and ARGI (6q22.3-q23.1),

  16. Controlli societari e posizioni di garanzia. Un'indagine alla luce del d.lgs. 231/2001

    OpenAIRE

    Molinaro, Claudia

    2016-01-01

    The research aims to examine the impact of Legislative Decree 231/2001, which has established a regulation of criminal compliance and liability of corporations, on the responsibility for the omission to prevent crimes of the members of corporate bodies entrusted to adopt and put into effects compliance programs, and to monitor the operation of such programs. The first part of the thesis contains a doctrinal analysis, which intends to define the requirements of omission to act, with particu...

  17. Substantial reduction of the gastric carcinoma critical region at 6q16.3-q23.1

    NARCIS (Netherlands)

    Carvalho, B; Seruca, R; Carneiro, F; Buys, CHCM; Kok, K

    1999-01-01

    Deletions of the long arm of chromosome 6 are a common event in gastric carcinomas. In a previous study, deletion mapping of 6q identified two smallest regions of overlap (SROs) of heterozygous deletions: one interstitial, spanning 12-16 cM, bordered by D6S268 (6q16.3-q21) and ARGI (6q22.3-q23.1), a

  18. Antitumor Activity of Chinese Propolis in Human Breast Cancer MCF-7 and MDA-MB-231 Cells

    Directory of Open Access Journals (Sweden)

    Hongzhuan Xuan

    2014-01-01

    Full Text Available Chinese propolis has been reported to possess various biological activities such as antitumor. In present study, anticancer activity of ethanol extract of Chinese propolis (EECP at 25, 50, 100, and 200 μg/mL was explored by testing the cytotoxicity in MCF-7 (human breast cancer ER(+ and MDA-MB-231 (human breast cancer ER(− cells. EECP revealed a dose- and time-dependent cytotoxic effect. Furthermore, annexin A7 (ANXA7, p53, nuclear factor-κB p65 (NF-κB p65, reactive oxygen species (ROS levels, and mitochondrial membrane potential were investigated. Our data indicated that treatment of EECP for 24 and 48 h induced both cells apoptosis obviously. Exposure to EECP significantly increased ANXA7 expression and ROS level, and NF-κB p65 level and mitochondrial membrane potential were depressed by EECP dramatically. The effects of EECP on p53 level were different in MCF-7 and MDA-MB-231 cells, which indicated that EECP exerted its antitumor effects in MCF-7 and MDA-MB-231 cells by inducing apoptosis, regulating the levels of ANXA7, p53, and NF-κB p65, upregulating intracellular ROS, and decreasing mitochondrial membrane potential. Interestingly, EECP had little or small cytotoxicity on normal human umbilical vein endothelial cells (HUVECs. These results suggest that EECP is a potential alternative agent on breast cancer treatment.

  19. 235U–231Pa age dating of uranium materials for nuclear forensic investigations

    Energy Technology Data Exchange (ETDEWEB)

    Eppich, Gary R. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Williams, Ross W. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Gaffney, Amy M. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Schorzman, Kerri C. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2013-04-03

    Here, age dating of nuclear material can provide insight into source and suspected use in nuclear forensic investigations. We report here a method for the determination of the date of most recent chemical purification for uranium materials using the 235U-231Pa chronometer. Protactinium is separated from uranium and neptunium matrices using anion exchange resin, followed by sorption of Pa to an SiO2 medium. The concentration of 231Pa is measured by isotope dilution mass spectrometry using 233Pa spikes prepared from an aliquot of 237Np and calibrated in-house using the rock standard Table Mountain Latite and the uranium isotopic standard U100. Combined uncertainties of age dates using this method are 1.5 to 3.5 %, an improvement over alpha spectrometry measurement methods. Model ages of five uranium standard reference materials are presented; all standards have concordant 235U-231Pa and 234U-230Th model ages.

  20. Phosphorylation of tau at both Thr 231 and Ser 262 is required for maximal inhibition of its binding to microtubules.

    Science.gov (United States)

    Sengupta, A; Kabat, J; Novak, M; Wu, Q; Grundke-Iqbal, I; Iqbal, K

    1998-09-15

    The paired helical filaments (PHFs) found in Alzheimer's disease (AD) brains are composed primarily of the microtubule-associated protein tau. PHF-tau is in a hyperphosphorylated state and is unable to promote microtubule assembly. We investigated whether the inhibition of tau binding to microtubules is increased when tau is phosphorylated by different kinases in combination with GSK-3. We found that when tau was first phosphorylated by A-kinase, C-kinase, cdk5, or CaM kinase II and then by GSK-3, its binding to microtubules was inhibited by 45, 61, 78, and 79%, respectively. Further, the kinase combinations cdk5/GSK-3 and CaM kinase II/GSK-3 rapidly phosphorylated the sites Thr 231 and Ser 235. When these sites were individually replaced by Ala and the phosphorylation experiments repeated, tau binding to microtubules was inhibited by 54 and 71%, respectively. By comparison, when Ser 262 was replaced by Ala, tau binding to microtubules was inhibited by only 8% after phosphorylation by CaM kinase II. From these observations we estimate that the phosphorylation of Thr 231, Ser 235, and Ser 262 contributes approximately 26, approximately 9, and approximately 33%, respectively, of the overall inhibition of tau binding to microtubules. Together, our results indicate that the binding of tau to microtubules is controlled by the phosphorylation of several sites, among which are Thr 231, Ser 235, and Ser 262.

  1. Differential Epigenetic Effects of Atmospheric Cold Plasma on MCF-7 and MDA-MB-231 Breast Cancer Cells.

    Science.gov (United States)

    Park, Sung-Bin; Kim, Byungtak; Bae, Hansol; Lee, Hyunkyung; Lee, Seungyeon; Choi, Eun H; Kim, Sun Jung

    2015-01-01

    Cold atmospheric plasma (plasma) has emerged as a novel tool for a cancer treatment option, having been successfully applied to a few types of cancer cells, as well as tissues. However, to date, no studies have been performed to examine the effect of plasma on epigenetic alterations, including CpG methylation. In this study, the effects of plasma on DNA methylation changes in breast cancer cells were examined by treating cultured MCF-7 and MDA-MB-231 cells, representing estrogen-positive and estrogen-negative cancer cells, respectively, with plasma. A pyrosequencing analysis of Alu indicated that a specific CpG site was induced to be hypomethylated from 23.4 to 20.3% (p plasma treatment in the estrogen-negative MDA-MB-231 cells only. A genome-wide methylation analysis identified "cellular movement, connective tissue development and function, tissue development" and "cell-to-cell signaling and interaction, cell death and survival, cellular development" as the top networks. Of the two cell types, the MDA-MB-231 cells underwent a higher rate of apoptosis and a decreased proliferation rate upon plasma treatment. Taken together, these results indicate that plasma induces epigenetic and cellular changes in a cell type-specific manner, suggesting that a careful screening of target cells and tissues is necessary for the potential application of plasma as a cancer treatment option.

  2. Differential Epigenetic Effects of Atmospheric Cold Plasma on MCF-7 and MDA-MB-231 Breast Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Sung-Bin Park

    Full Text Available Cold atmospheric plasma (plasma has emerged as a novel tool for a cancer treatment option, having been successfully applied to a few types of cancer cells, as well as tissues. However, to date, no studies have been performed to examine the effect of plasma on epigenetic alterations, including CpG methylation. In this study, the effects of plasma on DNA methylation changes in breast cancer cells were examined by treating cultured MCF-7 and MDA-MB-231 cells, representing estrogen-positive and estrogen-negative cancer cells, respectively, with plasma. A pyrosequencing analysis of Alu indicated that a specific CpG site was induced to be hypomethylated from 23.4 to 20.3% (p < 0.05 by plasma treatment in the estrogen-negative MDA-MB-231 cells only. A genome-wide methylation analysis identified "cellular movement, connective tissue development and function, tissue development" and "cell-to-cell signaling and interaction, cell death and survival, cellular development" as the top networks. Of the two cell types, the MDA-MB-231 cells underwent a higher rate of apoptosis and a decreased proliferation rate upon plasma treatment. Taken together, these results indicate that plasma induces epigenetic and cellular changes in a cell type-specific manner, suggesting that a careful screening of target cells and tissues is necessary for the potential application of plasma as a cancer treatment option.

  3. Cytotoxic effect of sanguiin H-6 on MCF-7 and MDA-MB-231 human breast carcinoma cells.

    Science.gov (United States)

    Park, Eun-Ji; Lee, Dahae; Baek, Seon-Eun; Kim, Ki Hyun; Kang, Ki Sung; Jang, Tae Su; Lee, Hye Lim; Song, Ji Hoon; Yoo, Jeong-Eun

    2017-09-15

    Sanguiin H-6 is a dimer of casuarictin linked by a bond between the gallic acid residue and one of the hexahydroxydiphenic acid units. It is an effective compound extracted from Rubus coreanus. It has an anticancer effect against several human cancer cells; however, its effect on breast cancer cells has not been clearly demonstrated. Thus, we aimed to investigate the anticancer effect and mechanism of action of sanguiin H-6 against two human breast carcinoma cell lines (MCF-7 and MDA-MB-231). We found that sanguiin H-6 significantly reduced cell viability in a concentration-dependent manner. It also increased the rates at which MCF-7 and MDA-MB-231 cells underwent apoptosis. Furthermore, sanguiin H-6 induced the cleavage of caspase-8, caspase-3, and poly(ADP-ribose) polymerase, which resulted in apoptosis. However, cleavage of caspase-9 was only detectable in MCF-7 cells. In addition, sanguiin H-6 increased the ratio of Bax to Bcl-2 in both MCF-7 and MDA-MB-231 cells. These findings suggest that sanguiin H-6 is a potent therapeutic agent against breast cancer cells. In addition, it exerts its anticancer effect in an estrogen-receptor-independent manner. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Analysis of Protein–Protein Interactions in MCF-7 and MDA-MB-231 Cell Lines Using Phthalic Acid Chemical

    Directory of Open Access Journals (Sweden)

    Shih-Shin Liang

    2014-11-01

    Full Text Available Phthalates are a class of plasticizers that have been characterized as endocrine disrupters, and are associated with genital diseases, cardiotoxicity, hepatotoxicity, and nephrotoxicity in the GeneOntology gene/protein database. In this study, we synthesized phthalic acid chemical probes and demonstrated differing protein–protein interactions between MCF-7 cells and MDA-MB-231 breast cancer cell lines. Phthalic acid chemical probes were synthesized using silicon dioxide particle carriers, which were modified using the silanized linker 3-aminopropyl triethoxyslane (APTES. Incubation with cell lysates from breast cancer cell lines revealed interactions between phthalic acid and cellular proteins in MCF-7 and MDA-MB-231 cells. Subsequent proteomics analyses indicated 22 phthalic acid-binding proteins in both cell types, including heat shock cognate 71-kDa protein, ATP synthase subunit beta, and heat shock protein HSP 90-beta. In addition, 21 MCF-7-specific and 32 MDA-MB-231 specific phthalic acid-binding proteins were identified, including related proteasome proteins, heat shock 70-kDa protein, and NADPH dehydrogenase and ribosomal correlated proteins, ras-related proteins, and members of the heat shock protein family, respectively.

  5. Regulation of MDA-MB-231 cell proliferation by GSK-3β involves epigenetic modifications under high glucose conditions.

    Science.gov (United States)

    Gupta, Chanchal; Kaur, Jasmine; Tikoo, Kulbhushan

    2014-05-15

    Hyperglycemia is a critical risk factor for development and progression of breast cancer. We have recently reported that high glucose induces phosphorylation of histone H3 at Ser 10 as well as de-phosphorylation of GSK-3β at Ser 9 in MDA-MB-231 cells. Here, we elucidate the mechanism underlying hyperglycemia-induced proliferation in MDA-MB-231 breast cancer cells. We provide evidence that hyperglycemia led to increased DNA methylation and DNMT1 expression in MDA-MB-231 cells. High glucose condition led to significant increase in the expression of PCNA, cyclin D1 and decrease in the expression of PTPN 12, p21 and PTEN. It also induced hypermethylation of DNA at the promoter region of PTPN 12, whereas hypomethylation at Vimentin and Snail. Silencing of GSK-3β by siRNA prevented histone H3 phosphorylation and reduced DNMT1 expression. We show that chromatin obtained after immunoprecipitation with phospho-histone H3 was hypermethylated under high glucose condition, which indicates a cross-talk between DNA methylation and histone H3 phosphorylation. ChIP-qPCR analysis revealed up-regulation of DNMT1 and metastatic genes viz. Vimentin, Snail and MMP-7 by phospho-histone H3, which were down-regulated upon GSK-3β silencing. To the best of our knowledge, this is the first report which shows that interplay between GSK-3β activation, histone H3 phosphorylation and DNA methylation directs proliferation of breast cancer cells.

  6. Models of the Hydrodynamic Histories of Post-AGB Stars. I. Multiflow Shaping of OH 231.8+04.2

    Science.gov (United States)

    Balick, Bruce; Frank, Adam; Liu, Baowei; Huarte-Espinosa, Martín

    2017-07-01

    We present a detailed hydrodynamic model that matches the present structure of the well-observed preplanetary nebula (“pPN”) OH 231.8+04.2 (“OH231”). The purpose of the model is to present a physically justified and coherent picture of its evolutionary history from about 100 years from the start of the formation of its complex outer structures to the present. We have adopted a set of initial conditions that are heavily constrained by high-quality observations of its present structure and kinematics. The shaping of the nebula occurs while the densities of the flows are “light,” i.e., less than the surrounding AGB-wind environment. The simulations show that pairs of essentially coeval clumps and sprays of the same extent and density, but different outflow speeds, sculpted both the pair of thin axial flow “or spine” and the bulbs. The total ejected mass and momentum in the best-fit model are surprisingly large—3 M ⊙ and 2.2 × 1041 gm cm s-1, respectively—however, these values are reduced by up to a factor of 10 in other models that fit the data almost as well. Our ultimate goal is to combine the present model results of masses, momenta, flow speeds, and flow geometries for OH231 with those of other models to be published in the future in order to find common attributes of their ejection histories.

  7. Deleterious effects on MDAMB-231 breast adenocarcinoma cell lineage submitted to Ho-166 radioactive seeds at very low activity

    Energy Technology Data Exchange (ETDEWEB)

    Falcao, Patricia L.; Campos, Tarcisio P.R., E-mail: campos@nuclear.ufmg.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Engenharia Nuclear; Sarmento, Eduardo V. [Centro de Desenvolvimento de Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Cuperschmid, Ethel M. [Universidade Federal de Minas Gerais (CEMEMOR/UFMG), Belo Horizonte, BR (Brazil). Fac. de Medicina. Centro de Memoria da Medicina

    2011-07-01

    Herein, the deleterious effect of ionizing radiation provided by Ho-166 radioactive seeds at low activity were addressed, based on experimental in vitro assays at the MDA MB231 cell lineage, a breast adenocarcinoma, compared to PBMC - peripheral blood cells. The methodology involves of the MDBMB-231 and PBMC expansion in culture in suitable environment in 30mm well plates and T-25 flasks. Seeds were synthesized with Ho-165 incorporated and characterized previously. Activation was processed at IPR1 reactor at the peripheral table, at 8h exposition. Three groups of seeds were tested: 0,34 mCi, 0,12 mCi activity, and control group. Such seeds were placed on culture and held to a period of 05 half-lives of the radionuclide. The biological responses at these exposure were documented by inverse microscopic photographic in time. Also, MTT essay were performed. A fast response in producing deleterious effects at cancer cell was observed even if for the low activity seeds. Also, a biological response dependent to a radial distance of the seed was observed. At conclusion, viability clonogenic control of MDAMB231 is identified at the exposition to Ho-166 ceramic seeds, even if at low activity of 0,1 to 0,3mCi. (author)

  8. Medium Renewal Blocks Anti-Proliferative Effects of Metformin in Cultured MDA-MB-231 Breast Cancer Cells.

    Science.gov (United States)

    Rajh, Maruša; Dolinar, Klemen; Miš, Katarina; Pavlin, Mojca; Pirkmajer, Sergej

    2016-01-01

    Epidemiological studies indicate that metformin, a widely used type 2 diabetes drug, might reduce breast cancer risk and mortality in patients with type 2 diabetes. Metformin might protect against breast cancer indirectly by ameliorating systemic glucose homeostasis. Alternatively, it might target breast cancer cells directly. However, experiments using MDA-MB-231 cells, a standard in vitro breast cancer model, produced inconsistent results regarding effectiveness of metformin as a direct anti-cancer agent. Metformin treatments in cultured MDA-MB-231 cells are usually performed for 48-96 hours, but protocols describing renewal of cell culture medium during these prolonged treatments are rarely reported. We determined whether medium renewal protocol might alter sensitivity of MDA-MB-231 cells treated with metformin. Using the MTS assay, BrdU incorporation and Hoechst staining we found that treatment with metformin for 48-72 hours failed to suppress viability and proliferation of MDA-MB-231 cells if low-glucose (1 g/L) medium was renewed every 24 hours. Conversely, metformin suppressed their viability and proliferation if medium was not renewed. Without renewal glucose concentration in the medium was reduced to 0.1 g/L in 72 hours, which likely explains increased sensitivity to metformin under these conditions. We also examined whether 2-deoxy-D-glucose (2-DG) reduces resistance to metformin. In the presence of 2-DG metformin reduced viability and proliferation of MDA-MB-231 cells with or without medium renewal, thus demonstrating that 2-DG reduces their resistance to metformin. In sum, we show that medium renewal blocks anti-proliferative effects of metformin during prolonged treatments in low-glucose medium. Differences in medium renewal protocols during prolonged treatments might therefore lead to apparently inconsistent results as regards effectiveness of metformin as a direct anti-cancer agent. Finally, our results indicate that co-therapy with 2-DG and

  9. Medium Renewal Blocks Anti-Proliferative Effects of Metformin in Cultured MDA-MB-231 Breast Cancer Cells

    Science.gov (United States)

    Rajh, Maruša; Dolinar, Klemen; Miš, Katarina; Pavlin, Mojca; Pirkmajer, Sergej

    2016-01-01

    Epidemiological studies indicate that metformin, a widely used type 2 diabetes drug, might reduce breast cancer risk and mortality in patients with type 2 diabetes. Metformin might protect against breast cancer indirectly by ameliorating systemic glucose homeostasis. Alternatively, it might target breast cancer cells directly. However, experiments using MDA-MB-231 cells, a standard in vitro breast cancer model, produced inconsistent results regarding effectiveness of metformin as a direct anti-cancer agent. Metformin treatments in cultured MDA-MB-231 cells are usually performed for 48–96 hours, but protocols describing renewal of cell culture medium during these prolonged treatments are rarely reported. We determined whether medium renewal protocol might alter sensitivity of MDA-MB-231 cells treated with metformin. Using the MTS assay, BrdU incorporation and Hoechst staining we found that treatment with metformin for 48–72 hours failed to suppress viability and proliferation of MDA-MB-231 cells if low-glucose (1 g/L) medium was renewed every 24 hours. Conversely, metformin suppressed their viability and proliferation if medium was not renewed. Without renewal glucose concentration in the medium was reduced to 0.1 g/L in 72 hours, which likely explains increased sensitivity to metformin under these conditions. We also examined whether 2-deoxy-D-glucose (2-DG) reduces resistance to metformin. In the presence of 2-DG metformin reduced viability and proliferation of MDA-MB-231 cells with or without medium renewal, thus demonstrating that 2-DG reduces their resistance to metformin. In sum, we show that medium renewal blocks anti-proliferative effects of metformin during prolonged treatments in low-glucose medium. Differences in medium renewal protocols during prolonged treatments might therefore lead to apparently inconsistent results as regards effectiveness of metformin as a direct anti-cancer agent. Finally, our results indicate that co-therapy with 2-DG and

  10. Low-dose irradiation promotes proliferation of the human breast cancer MDA-MB-231 cells through accumulation of mutant P53.

    Science.gov (United States)

    Li, Si-Jie; Liang, Xin-Yue; Li, Hai-Jun; Li, Wei; Zhou, Lei; Chen, Hua-Qiu; Ye, Song-Gen; Yu, De-Hai; Cui, Jiu-Wei

    2017-01-01

    Low-dose irradiation (LDIR) has been proven to have differential biological effects on normal mammalian somatic cells and cancer cells. Our previous study showed that p53 gene status is a critical factor regulating the effect of LDIR on cancer cells. We investigated the effect of LDIR on the breast cancer cell line MDA-MB-231 that harbors a mutant p53 gene, and the normal breast fibroblast cell line Hs 578Bst. In the present study, we showed that 150 mGy LDIR pormoted growth of MDA-MB-231 cells but not Hs 578Bst cells. Through cell cycle analyses, we found that LDIR accelerated cell cycle into S phase in MDA-MB-231 cells, but did not affect the cell cycle of Hs 578Bst cells. Using western blotting, we demonstrated that the expression of CDK4, CDK6 and cyclin D1 was upregulated in MDA-MB-231 cells after LDIR. Although LDIR increased ataxia-telangiectasia mutated (ATM) level in both MDA-MB-231 cells and Hs 578Bst cells and activated ATM/p53/p21 pathway, only the mutant type of p53 (mtp53) protein in MDA-MB-231 cells was shown to be accumulated after LDIR. Using ATM inhibitor or lentivirus-mediated small interfering RNA (siRNA) to block the ATM/p53/p21 pathway in MDA-MB-231 cells, the LDIR-induced cell proliferation was abolished. When we introduced wild-type p53 (wtp53) protein into MDA-MB-231 cells, the LDIR-induced cell proliferation was also abolished. These findings suggest that normal p53 function is crucial in ATM/p53/p21 pathway activated by LDIR. The p53 status is the most probable reason leading to differential LDIR biological activities between breast tumor cells and normal breast cells.

  11. Gene expression profiling and pathway analysis data in MCF-7 and MDA-MB-231 human breast cancer cell lines treated with dioscin.

    Science.gov (United States)

    Aumsuwan, Pranapda; Khan, Shabana I; Khan, Ikhlas A; Walker, Larry A; Dasmahapatra, Asok K

    2016-09-01

    Microarray technology (Human OneArray microarray, phylanxbiotech.com) was used to compare gene expression profiles of non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cells exposed to dioscin (DS), a steroidal saponin isolated from the roots of wild yam, (Dioscorea villosa). Initially the differential expression of genes (DEG) was identified which was followed by pathway enrichment analysis (PEA). Of the genes queried on OneArray, we identified 4641 DEG changed between MCF-7 and MDA-MB-231 cells (vehicle-treated) with cut-off log2 |fold change|≧1. Among these genes, 2439 genes were upregulated and 2002 were downregulated. DS exposure (2.30 μM, 72 h) to these cells identified 801 (MCF-7) and 96 (MDA-MB-231) DEG that showed significant difference when compared with the untreated cells (pMB-231 cells. Further comparison of DEG between MCF-7 and MDA-MB-231 cells exposed to DS identified 3626 DEG of which 1700 were upregulated and 1926 were down-regulated. Regarding to PEA, 12 canonical pathways were significantly altered between these two cell lines. However, there was no alteration in any of these pathways in MCF-7 cells, while in MDA-MB-231 cells only MAPK pathway showed significant alteration. When PEA comparison was made on DS exposed cells, it was observed that only 2 pathways were significantly affected. Further, we identified the shared DEG, which were targeted by DS and overlapped in both MCF-7 and MDA-MB-231 cells, by intersection analysis (Venn diagram). We found that 7 DEG were overlapped of which six are reported in the database. This data highlight the diverse gene networks and pathways in MCF-7 and MDA-MB-231 human breast cancer cell lines treated with dioscin.

  12. PDTC联合紫杉醇降低MDA-MB-231细胞增殖侵袭能力%Combination of pyrrolidine dithiocarbamate and paclitaxel suppresses proliferation and invasion of MDA-MB-231 cells

    Institute of Scientific and Technical Information of China (English)

    杨春蓉; 张徽; 黃伟; 刘琼

    2010-01-01

    目的 探讨核因子-κB(NF-κB)抑制剂--吡咯烷二硫代氨基甲酸盐(pyrrolidine dithiocarbamate,PDTC)联合紫杉醇(Paclitaxel)对人乳腺癌MDA-MB-231细胞增殖侵袭能力的影响.方法 MTT及FCM法测定细胞增殖和周期变化,RT-PCR检测细胞NF-κB p65 mRNA的变化,Western blot检测细胞NF-κB p65、MMP-9及TIMP-1蛋白表达变化,侵袭、迁移和黏附实验测定细胞侵袭转移能力的改变.结果 PDTC联合紫杉醇能明显抑制肿瘤细胞生长(P<0.05),细胞周期阻滞在G_1/G_0期,并可抵消紫杉醇对NF-κB的激活,使NF-κB p65 mRNA及蛋白的表达均降低(P<0.05).PDTC降低MDA-MB-231细胞的侵袭转移能力,与紫杉醇联合应用后作用增强(P<0.01).结论 PDTC联合紫杉醇能降低乳腺癌MDA-MB-231细胞的侵袭转移能力,其机制可能与PDTC抑制NF-κB的表达相关.

  13. Analysis of the Risk Factors Related with Diabetes among 231 Peoples who were 49 -51 Years Old%49~51岁231例糖尿病相关危险因素的临床分析

    Institute of Scientific and Technical Information of China (English)

    田坚; 赵晓伟

    2011-01-01

    目的:对沈阳市铁西区49 ~51岁的231例研究对象进行糖尿病(diabetes mellitus,DM)相关危险因素的调查分析.方法:选取1959~1961年出生的231人为研究对象,男116人,女115人,行75g葡萄糖耐量实验(oral glucose tolerance test,OGTT)、胰岛素或C肽释放试验,糖化血红蛋白、血脂、肝肾功能,以及血压、体重测定.结果:分析231例研究对象的血糖、血脂、血压、体重指数(body mass index,BMI)、血尿酸各项指标,以高甘油三酯血症最高,占53.2%,次为肥胖BMI> 25 kg/m2,占43.7%,高尿酸血症占34.6%.结论:该年龄者因普遍存在出生时营养欠佳,成年后生活方式改变,体重增加,存在糖脂代谢紊乱、肥胖症、高尿酸血症,提示是DM和心脑血管疾病的极高危人群.

  14. Sediment 231Pa/230Th as a recorder of the rate of the Atlantic meridional overturning circulation: insights from a 2-D model

    Directory of Open Access Journals (Sweden)

    S. E. Allen

    2010-03-01

    Full Text Available A two dimensional scavenging model is used to investigate the patterns of sediment 231Pa/230Th generated by the Atlantic Meridional Overturning Circulation (AMOC and further advance the application of this proxy for ocean paleocirculation studies. The scavenging parameters and the geometry of the overturning circulation cell have been chosen so that the model generates meridional sections of dissolved 230Th and 231Pa consistent with published water column profiles and an additional 12 previously unpublished profiles measured in the North and Equatorial Atlantic. The processes that generate the meridional sections of dissolved and particulate 230Th, dissolved and particulate 231Pa, dissolved and particulate 231Pa/230Th, and sediment 231Pa/230Th are discussed in detail. The results indicate that the relationship between sediment 231Pa/230Th at any given site and the overturning circulation is very complex. They clearly show that constraining past changes in the strength and geometry of the AMOC requires an extensive data set and they suggest strategies to maximize information from a limited number of samples.

  15. Sediment 231Pa/230Th as a recorder of the rate of the Atlantic meridional overturning circulation: insights from a 2-D model

    Directory of Open Access Journals (Sweden)

    S. E. Allen

    2009-11-01

    Full Text Available A two dimensional scavenging-circulation model is used to investigate the patterns of sediment 231Pa/230Th generated by the Atlantic Meridional Overturning Circulation (AMOC and further advance the application of this proxy for ocean paleocirculation studies. The scavenging parameters and the geometry of the overturning circulation cell have been chosen so that the model generates meridional sections of dissolved 230Th and 231Pa consistent with published water column profiles and an additional 12 previously unpublished profiles measured in the North and Equatorial Atlantic. The processes that generate the meridional sections of dissolved and particulate 230Th, dissolved and particulate 231Pa, dissolved and particulate 231Pa/230Th, and sediment 231Pa/230Th are discussed in detail. The results indicate that the relationship between sediment 231Pa/230Th at any given site and the overturning circulation is very complex. They clearly show that constraining past changes in the strength and geometry of the AMOC requires an extensive data set and they suggest strategies to maximize information from a limited number of samples.

  16. Radiosensitizing effect of conjugated linoleic acid in MCF-7 and MDA-MB-231 breast cancer cells; Effet radiosensibilisateur de l'acide linoleique conjugue chez les cellules cancereuses de sein MCF-7 et MDA-MB-231

    Energy Technology Data Exchange (ETDEWEB)

    Drouin, G.; Douillette, A. [Univ. de Sherbrooke, Dept. de medecine nucleaire de radiobiologie, Faculte de medecine, Sherbrooke, Quebec (Canada); Lacasse, P. [Centre de recherche et development sur le bovin laitier et le porc, Lennoxville, Quebec (Canada); Paquette, B. [Univ. de Sherbrooke, Dept. de medecine nucleaire de radiobiologie, Faculte de medecine, Sherbrooke, Quebec (Canada)]. E-mail: benoit.paquette@USherbrooke.ca

    2004-02-01

    Apoptotic pathways in breast cancer cells are frequently altered, reducing the efficiency of radiotherapy. Conjugated linoleic acid (CLA), known to trigger apoptosis, was tested as radiosensitizer in breast cancer cells MCF-7 and MDA-MB-231. The CLA-mix, made up of the isomers CLA-9cis 11trans and CLA-10trans 12cis, was compared to three purified isomers, i.e., the CLA-9cis 11cis, CLA-9cis 11trans, and CLA-10trans 12cis. Using the apoptotic marker YO-PRO-1, the CLA-9cis 11cis at 50 {mu}mol/L turned out to be the best apoptotic inducer leading to a 10-fold increase in MCF-7 cells and a 2,5-fold increase in MDA-MB-231 cells, comparatively to the CLA-mix. Contrary to previous studies on colorectal and prostate cancer cells, CLA-10trans 12cis does not lead to an apoptotic response on breast cancer cell lines MCF-7 and MDA-MB-231. Our results also suggest that the main components of the CLA-mix (CLA-9cis 11trans and CLA-10trans 12cis) are not involved in the induction of apoptosis in the breast cancer cells studied. A dose of 5 Gy did not induce apoptosis in MCF-7 and MDA-MB-231 cells. The addition of CLA-9cis 11cis or CLA-mix has allowed us to observe a radiation-induced apoptosis, with the CLA-9cis 11cis being about 8-fold better than the CLA-mix. CLA-9cis 11cis turned out to be the best radiosensitizer, although the isomers CLA-9cis 11trans and CLA-10trans 12cis have also reduced the cell survival following irradiation, but using a mechanism not related to apoptosis. In conclusion, the radiosensitizing property of CLA-9cis 11cis supports its potential as an agent to improve radiotherapy against breast carcinoma. (author)

  17. [Effect of down-regulation of Oct4 gene on biological characteristics of MDA-MB-231 breast cancer stem cells].

    Science.gov (United States)

    2015-04-01

    To investigate the effect and significance of down-regulation of Oct4 gene on biological characteristics of MDA-MB-231 breast cancer stem cells. Breast cancer cell line MDA-MB-231 cells were used in this study. Breast cancer stem cells were isolated and enriched by serum-free culture. The obtained stem cells were identified through calculating the percentages of CD44 and CD24 stem cells by FACS and evaluating the paclitaxel resistance in vitro and tumorigenicity in mice. RT-PCR, real-time PCR (qPCR) and Western blot were used to detect Oct4 expression. RNA interference was applied to induce Oct4 down-regulation. The interference experiment set up a control group (no siRNA transfection), negative control group (negative siRNA group, transfection of siRNA sequences without any interfering effect on the cells) and Oct4 siRNA group (transfection of siRNA with interfering effect on the Oct4 gene). Methyl thiazolyl tetrazolium (MTT) and Transwell chamber tests were conducted to detect the proliferation and invasion ability of MDA-MB-231 breast cancer stem cells after Oct4 knock-down, and paclitaxel inhibition test was applied to evaluate drug resistance of MDA-MB-231 breast cancer stem cells after Oct4 knock-down. MDA-MB-231 breast cancer stem cells grew as spheres cultured in serum-free suspension. MDA-MB-231 breast cancer stem cells showed a higher percentage of CD44+/CD24-/low cells (97.2%) than that in MDA-MB-231 breast cancer cells (76.6%) (P MB-231 breast cancer stem cells was (124.60 ± 13.65) mm3, significantly larger than that of mice inoculated with breast cancer cells (68.20 ± 9.99 mm3) (P = 0.0007). MDA-MB-231 breast cancer stem cells were less sensitive to paclitaxel inhibition than MDA-MB-231 breast cancer cells showing by 50% inhibitory concentration (IC50) [(4.40 ± 0.48) µg/ml vs. (8.20 ± 0.34) µg/m, P MB-231 breast cancer stem cells than that in breast cancer cells (P MB-231 breast cancer stem cells with Oct4 siRNA interference was significantly

  18. Characterization of the glycosylation profile of the human breast cancer cell line, MDA-231, and a bone colonizing variant.

    Science.gov (United States)

    Carcel-Trullols, Jaime; Stanley, Joseph S; Saha, Rinku; Shaaf, Saeid; Bendre, Manali S; Monzavi-Karbassi, Behjatolah; Suva, Larry J; Kieber-Emmons, Thomas

    2006-05-01

    The mechanisms that guide organ-specific metastases are not fully established. The aberrant expression of carbohydrates may play a fundamental role in defining the molecular mechanisms for metastases to distant organs and facilitate positive interactions within the target organ. The purpose of the present study was to determine the glycomic profile of a variant of the MDA-MB-231 breast cancer cell line that colonizes the bone and to ascribe mechanistic functions mediated by carbohydrates that might correlate with clinical bone metastases. The carbohydrate expression profiles of osteolytic MDA-MET breast cancer cells and non-osteolytic parental MDA-MB-231 cells were determined. MDA-MET cells were derived from MDA-MB-231 cells by in vivo selection of metastatic bone lesions following intracardiac inoculation. The two related breast cancer cell lines expressed distinct carbohydrate profiles; MDA-MET cells displayed an increased expression of alpha (2,6) linked sialic acid, N-beta1-6 GlcNAc, and sialylated Lewis-A antigen, and decreased expression of Galbeta1,3GalNAc as detected using a combination of lectins and anti-carbohydrate antibodies. Microarray analysis demonstrated an increased expression of glycosyltransferase genes, correlative for the distinct glycomic phenotype. The altered glycomic phenotypes of MDA-MET cells include effects on the differential binding to bone marrow endothelial cells, enhanced ECM binding and an increase in invasive potential. These data suggest that the glycomic phenotype of MDA-MET cells is associated with a select set of accumulated functions that collectively impact on the bone metastases and bone colonization capacity of breast cancer cells.

  19. Radio-sensitization by Piper longumine of human breast adenoma MDA-MB-231 cells in vitro.

    Science.gov (United States)

    Yao, Jian-Xin; Yao, Zhi-Feng; Li, Zhan-Feng; Liu, Yong-Biao

    2014-01-01

    The current study investigated the effects of Piper longumine on radio-sensitization of human breast cancer MDA-MB-231 cells and underlying mechanisms. Human breast cancer MDA-MB-231 cells were cultured in vitro and those in logarithmic growth phase were selected for experiments divided into four groups: control, X-ray exposed, Piper longumine, and Piper longumine combined with X-rays. Conogenic assays were performed to determine the radio-sensitizing effects. Cell survival curves were fitted by single-hit multi-target model and then the survival fraction (SF), average lethal dose (D0), quasi-threshold dose (Dq) and sensitive enhancement ratio (SER) were calculated. Cell apoptosis was analyzed by flow cytometry (FCM).Western blot assays were employed for expression of apoptosis-related proteins (Bc1-2 and Bax) after treatment with Piper longumine and/or X-ray radiation. The intracellular reactive oxygen species (ROS) level was detected by FCM with a DCFH-DA probe. The cloning formation capacity was decreased in the group of piperlongumine plus radiation, which displayed the values of SF2, D0, Dq significantly lower than those of radiation alone group and the sensitive enhancement ratio (SER) of D0 was1.22 and 1.29, respectively. The cell apoptosis rate was increased by the combination treatment of Piper longumine and radiation. Piper longumine increased the radiation-induced intracellular levels of ROS. Compared with the control group and individual group, the combination group demonstrated significantly decreased expression of Bcl-2 with increased Bax. Piper longumine at a non-cytotoxic concentration can enhance the radio-sensitivity of MDA- MB-231cells, which may be related to its regulation of apoptosis-related protein expression and the increase of intracellular ROS level, thus increasing radiation-induced apoptosis.

  20. Cardiotoxin III suppresses MDA-MB-231 cell metastasis through the inhibition of EGF/EGFR-mediated signaling pathway.

    Science.gov (United States)

    Tsai, Pei-Chien; Hsieh, Chi-Ying; Chiu, Chien-Chih; Wang, Chih-Kuang; Chang, Long-Sen; Lin, Shinne-Ren

    2012-10-01

    Cardiotoxin III (CTX III), a basic polypeptide isolated from Naja naja atra venom, has been shown to exhibit anticancer activity. Epidermal growth factor (EGF) and its receptor, EGFR, play roles in cancer metastasis in various tumors. We use EGF as a metastatic inducer of MDA-MB-231 cells to investigate the effect of CTX III on cell migration. CTX III inhibited the EGF-induced activation of matrix metalloproteinase-9 (MMP-9), and further suppressed cell invasion and migration without obvious cellular cytotoxicity. CTX III suppressed EGF-induced nuclear factor-kappaB (NF-κB) nuclear translocation and also abrogated the EGF-induced phosphorylation of EGFR, phosphatidylinositol 3-kinase (PI3K)/Akt, and extracellular regulated kinase (ERK)1/2. In addition, CTX III similar to wortmannin (a PI3K inhibitor) and U0126 (an up-stream kinase regulating ERK1/2 inhibitor) attenuated cell migration and invasion induced by EGF. Furthermore, the EGFR inhibitor AG1478 inhibited EGF-induced MMP-9 expression, cell migration and invasion, as well as the activation of ERK1/2 and PI3K/Akt, suggesting that ERK1/2 and PI3K/Akt activation occur downstream of EGFR activation. These findings suggest that CTX III inhibited the EGF-induced invasion and migration of MDA-MB-231 cells via EGFR-dependent PI3K/Akt, ERK1/2, and NF-κB signaling, leading to the down-regulation of MMP-9 expression. These results provide a novel mechanism to explain the role of CTX III as a potent anti-metastatic agent in MDA-MB-231 cells.

  1. Ebstein anomaly: Genetic heterogeneity and association with microdeletions 1p36 and 8p23.1.

    Science.gov (United States)

    Digilio, Maria Cristina; Bernardini, Laura; Lepri, Francesca; Giuffrida, Maria Grazia; Guida, Valentina; Baban, Anwar; Versacci, Paolo; Capolino, Rossella; Torres, Barbara; De Luca, Alessandro; Novelli, Antonio; Marino, Bruno; Dallapiccola, Bruno

    2011-09-01

    Ebstein anomaly is an uncommon congenital heart defect (CHD), characterized by downward displacement of the tricuspid valve into the right ventricle. To uncover the genetic associations with Ebstein anomaly, we have searched chromosomal imbalances using standard cytogenetic and array-CGH analysis, and single gene conditions associated with syndromic Ebstein anomaly (with extracardiac anomalies), and screened GATA4 and NKX2.5 mutations in nonsyndromic patients (without extracardiac anomalies). Between January 1997 and September 2009, 44 consecutive patients with Ebstein anomaly were evaluated in two centers of Pediatric Cardiology. Ebstein anomaly was syndromic in 12 (27%) patients, and nonsyndromic in 32 (73%). A recognizable syndrome or complex was diagnosed by clinical criteria in seven patients. In one syndromic patient an 18q deletion was diagnosed by standard cytogenetic analysis. Array-CGH analysis performed in 10 of the 12 syndromic patients detected an interstitial deletion of about 4 Mb at 8p23.1 in one patient, and a deletion 1pter > 1p36.32/dup Xpter- > Xp22.32 in another patient. In the 28 of 32 nonsyndromic patients who underwent molecular testing, no mutation in GATA4 and NKX2.5 genes were detected. We conclude that Ebstein anomaly is a genetically heterogeneous defect, and that deletion 1p36 and deletion 8p23.1 are the most frequent chromosomal imbalances associated with Ebstein anomaly. Candidate genes include the GATA4 gene (in patients with del 8p23.1), NKX2.5 (based on published patients with isolated Ebstein anomaly) and a hypothetical gene in patients with del 1p36). Copyright © 2011 Wiley-Liss, Inc.

  2. Identification and characterization of functional risk variants for colorectal cancer mapping to chromosome 11q23.1.

    Science.gov (United States)

    Biancolella, Michela; Fortini, Barbara K; Tring, Stephanie; Plummer, Sarah J; Mendoza-Fandino, Gustavo A; Hartiala, Jaana; Hitchler, Michael J; Yan, Chunli; Schumacher, Fredrick R; Conti, David V; Edlund, Christopher K; Noushmehr, Houtan; Coetzee, Simon G; Bresalier, Robert S; Ahnen, Dennis J; Barry, Elizabeth L; Berman, Benjamin P; Rice, Judd C; Coetzee, Gerhard A; Casey, Graham

    2014-04-15

    Genome-wide association studies of colorectal cancer (CRC) have identified a number of common variants associated with modest risk, including rs3802842 at chromosome 11q23.1. Several genes map to this region but rs3802842 does not map to any known transcribed or regulatory sequences. We reasoned, therefore, that rs3802842 is not the functional single-nucleotide polymorphism (SNP), but is in linkage disequilibrium (LD) with a functional SNP(s). We performed ChIP-seq for histone modifications in SW480 and HCT-116 CRC cells, and incorporated ChIP-seq and DNase I hypersensitivity data available through ENCODE within a 137-kb genomic region containing rs3802842 on 11q23.1. We identified SNP rs10891246 in LD with rs3802842 that mapped within a bidirectional promoter region of genes C11orf92 and C11orf93. Following mutagenesis to the risk allele, the promoter demonstrated lower levels of reporter gene expression. A second SNP rs7130173 was identified in LD with rs3802842 that mapped to a candidate enhancer region, which showed strong unidirectional activity in both HCT-116 and SW480 CRC cells. The risk allele of rs7130173 demonstrated reduced enhancer activity compared with the common allele, and reduced nuclear protein binding affinity in electromobility shift assays compared with the common allele suggesting differential transcription factor (TF) binding. SNPs rs10891246 and rs7130173 are on the same haplotype, and expression quantitative trait loci (eQTL) analyses of neighboring genes implicate C11orf53, C11orf92 and C11orf93 as candidate target genes. These data imply that rs10891246 and rs7130173 are functional SNPs mapping to 11q23.1 and that C11orf53, C11orf92 and C11orf93 represent novel candidate target genes involved in CRC etiology.

  3. A simple quantitative model of macromolecular crowding effects on protein folding: Application to the murine prion protein(121-231)

    Science.gov (United States)

    Bergasa-Caceres, Fernando; Rabitz, Herschel A.

    2013-06-01

    A model of protein folding kinetics is applied to study the effects of macromolecular crowding on protein folding rate and stability. Macromolecular crowding is found to promote a decrease of the entropic cost of folding of proteins that produces an increase of both the stability and the folding rate. The acceleration of the folding rate due to macromolecular crowding is shown to be a topology-dependent effect. The model is applied to the folding dynamics of the murine prion protein (121-231). The differential effect of macromolecular crowding as a function of protein topology suffices to make non-native configurations relatively more accessible.

  4. Context dependent reversion of tumor phenotype by connexin-43 expression in MDA-MB231 cells and MCF-7 cells: Role of β-catenin/connexin43 association

    Energy Technology Data Exchange (ETDEWEB)

    Talhouk, Rabih S., E-mail: rtalhouk@aub.edu.lb [Department of Biology, Faculty of Arts and Sciences, American University of Beirut, P.O. Box 11-0236, Beirut (Lebanon); Fares, Mohamed-Bilal; Rahme, Gilbert J.; Hariri, Hanaa H.; Rayess, Tina; Dbouk, Hashem A.; Bazzoun, Dana; Al-Labban, Dania [Department of Biology, Faculty of Arts and Sciences, American University of Beirut, P.O. Box 11-0236, Beirut (Lebanon); El-Sabban, Marwan E., E-mail: me00@aub.edu.lb [Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, American University of Beirut, P.O. Box 11-0236, Beirut (Lebanon)

    2013-12-10

    Connexins (Cx), gap junction (GJ) proteins, are regarded as tumor suppressors, and Cx43 expression is often down regulated in breast tumors. We assessed the effect of Cx43 over-expression in 2D and 3D cultures of two breast adenocarcinoma cell lines: MCF-7 and MDA-MB-231. While Cx43 over-expression decreased proliferation of 2D and 3D cultures of MCF-7 by 56% and 80% respectively, MDA-MB-231 growth was not altered in 2D cultures, but exhibited 35% reduction in 3D cultures. C-terminus truncated Cx43 did not alter proliferation. Untransfected MCF-7 cells formed spherical aggregates in 3D cultures, and MDA-MB-231 cells formed stellar aggregates. However, MCF-7 cells over-expressing Cx43 formed smaller sized clusters and Cx43 expressing MDA-MB-231 cells lost their stellar morphology. Extravasation ability of both MCF-7 and MDA-MB-231 cells was reduced by 60% and 30% respectively. On the other hand, silencing Cx43 in MCF10A cells, nonneoplastic human mammary cell line, increased proliferation in both 2D and 3D cultures, and disrupted acinar morphology. Although Cx43 over-expression did not affect total levels of β-catenin, α-catenin and ZO-2, it decreased nuclear levels of β-catenin in 2D and 3D cultures of MCF-7 cells, and in 3D cultures of MDA-MB-231 cells. Cx43 associated at the membrane with α-catenin, β-catenin and ZO-2 in 2D and 3D cultures of MCF-7 cells, and only in 3D conditions in MDA-MB-231 cells. This study suggests that Cx43 exerts tumor suppressive effects in a context-dependent manner where GJ assembly with α-catenin, β-catenin and ZO-2 may be implicated in reducing growth rate, invasiveness, and, malignant phenotype of 2D and 3D cultures of MCF-7 cells, and 3D cultures of MDA-MB-231 cells, by sequestering β-catenin away from nucleus. - Highlights: • Cx43 over-expressing MCF-7 and MDA-MB-231 were grown in 2D and 3D cultures. • Proliferation and growth morphology were affected in a context dependent manner. • Extravasation ability of both MCF

  5. Expression of GATA3 in MDA-MB-231 triple-negative breast cancer cells induces a growth inhibitory response to TGFß.

    Directory of Open Access Journals (Sweden)

    Isabel M Chu

    Full Text Available Transforming growth factor (ß1TGFß1 can promote proliferation in late stage cancers but acts as a tumor suppressor in normal epithelial cells and in early stage cancers. Although, the TGFß pathway has been shown to play a key role in tumorigenesis and metastasis, only a limited number of models have been developed to understand this process. Here, we present a novel model system to discern this paradoxical role of TGFß1 using the MDA-MB-231 (MB-231 cell line. The MB-231 triple-negative breast cancer cell line has been extensively characterized and has been shown to continue to proliferate and undergo epithelial-to-mesenchymal transition (EMT upon TGFß1 stimulation. We have previously shown by microarray analysis that expression of GATA3 in MB-231 cells results in reprogramming of these cells from a basal to a luminal subtype associated with a reduction of metastasis and tumorigenesis when implanted as xenografts. We now demonstrate that GATA3 overexpression in these cells results in a reduction of TGFß1 response, reversal of EMT, and most importantly, restoration of sensitivity to the inhibitory effects on proliferation of TGFß1. Microarray analysis revealed that TGFß1 treatment resulted in reduction of several cell cycle effectors in 231-GATA3 cells but not in control cells. Furthermore, our microarray analysis revealed a significant increase of BMP5 in 231-GATA3 cells. We demonstrate that combined treatment of MB-231 control cells with TGFß1 and BMP5 results in a significant reduction of cellular proliferation. Thus, this model offers a means to further investigate potentially novel mechanisms involved in the switch in response to TGFß1 from tumor promoter to tumor suppressor through the reprogramming of a triple-negative breast cancer cell line by the GATA3 transcription factor.

  6. Silencing of DUSP6 gene by RNAi-mediation inhibits proliferation and growth in MDA-MB-231 breast cancer cells: an in vitro study.

    Science.gov (United States)

    Song, Hongming; Wu, Chenyang; Wei, Chuankui; Li, Dengfeng; Hua, Kaiyao; Song, Jialu; Xu, Hui; Chen, Lei; Fang, Lin

    2015-01-01

    Dual-specificity phosphatase 6 (DUSP6) is a negative feedback mechanism of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), that is associated with cellular proliferation and differentiation. It has been reported that the expression of DUSP6 in different types of breast cancer is diverse and therefore it has altered functions in various types of breast cancer. Our aim was to explore the exact function of DUSP6 in triple-negative breast cancer cells (MDA-MB-231 cell) and to determine whether the suppression of DUSP6 by small interfering RNA (siRNA) and mircroRNA (miRNA) inhibits the growth of human MDA-MB-231 breast cancer cells. DUSP6-siRNA was used to inhibit the expression of DUSP6 directly and miR-145 to inhibit the expression of DUSP6 either in MDA-MB-231 breast cancer cells and successful transfection being confirmed by Real-time PCR and Western Blotting. Down regulation of DUSP6 in MDA-MB-231 cells suppressed the cell proliferation as investigated by MTT assay and colony form assay. Transwell test and Scratch assay were conducted to investigate the migration and invasion of MDA-MB-231 cells. T-test (two-tailed) was used to compare differences between groups, and the significance level was set at PMB-231 cells proliferation, migration and invasion, and meanwhile the cells were arrested at G0/G1 phase. DUSP6 plays a role in triple-negative breast cancer cells that might promote growth in MDA-MB-231 triple-negative breast cancer cells.

  7. [Establishment of breast cancer MDA-MB-231 cell line stably over-expressing human TOX high mobility group box family member 3].

    Science.gov (United States)

    Han, Cuicui; Yue, Liling; Yang, Ying; Jian, Baiyu; Ma, Liwei; Liu, Jicheng

    2014-11-01

    To construct the lentiviral expression vector of human TOX high mobility group box family member 3 (TOX3) gene and the MDA-MB-231 cell line which stably over-expresses TOX3 gene. TOX3 gene was synthesized by the gene synthesis method and amplified by PCR, and then cloned into pLVEF-1a/GFP-Puro vector to construct pLVEF-1a/GFP-Puro-TOX3 lentiviral vector. After restriction enzyme analysis and sequence identification, the lentiviral vector was packaged and the titer was detected. The human breast cancer MDA-MB-231 cells were transfected with the recombinant lentiviral vector and cultured selectively by puromycin to acquire stably transfected cells. MDA-MB-231 cells which expressed GFP were observed by fluorescence microcopy. And the expression levels of TOX3 mRNA and protein in transfected MDA-MB-231 cells were detected by real-time quantitative PCR(qRT-PCR) and Western blotting, respectively. Restriction enzyme digestion and sequence analysis demonstrated that the lentiviral expression vectors of pLVEF-1a/GFP-Puro and pLVEF-1a/GFP-Puro-TOX3 were successfully constructed, and the viral titers were respectively 2×10(8) TU/mL and 1×10(8) TU/mL after lentiviral packaging. And after being transfected, more than 95% cells expressed GFP under a fluorescence microscope. The results of qRT-PCR and Western blotting showed that, when compared with the MDA-MB-231-NC negative control group, the expression of TOX3 mRNA and protein significantly increased in the MDA-MB-231-TOX3 group. The study successfully constructed lentiviral expression vector of TOX3 gene and obtained MDA-MB-231 cell line stably over-expressing TOX3 gene by transfection with the recombinant vector.

  8. Effects of Different Zinc Species on Cellar Zinc Distribution, Cell Cycle, Apoptosis and Viability in MDAMB231 Cells.

    Science.gov (United States)

    Wang, Yan-hong; Zhao, Wen-jie; Zheng, Wei-juan; Mao, Li; Lian, Hong-zhen; Hu, Xin; Hua, Zi-chun

    2016-03-01

    Intracellular metal elements exist in mammalian cells with the concentration range from picomoles per litre to micromoles per litre and play a considerable role in various biological procedures. Element provided by different species can influence the availability and distribution of the element in a cell and could lead to different biological effects on the cell's growth and function. Zinc as an abundant and widely distributed essential trace element, is involved in numerous and relevant physiological functions. Zinc homeostasis in cells, which is regulated by metallothioneins, zinc transporter/SLC30A, Zrt-/Irt-like proteins/SLC39A and metal-response element-binding transcription factor-1 (MTF-1), is crucial for normal cellular functioning. In this study, we investigated the influences of different zinc species, zinc sulphate, zinc gluconate and bacitracin zinc, which represented inorganic, organic and biological zinc species, respectively, on cell cycle, viability and apoptosis in MDAMB231 cells. It was found that the responses of cell cycle, apoptosis and death to different zinc species in MDAMB231 cells are different. Western blot analysis of the expression of several key proteins in regulating zinc-related transcription, cell cycle, apoptosis, including MTF-1, cyclin B1, cyclin D1, caspase-8 and caspase-9 in treated cells further confirmed the observed results on cell level.

  9. Methylene blue, curcumin and ion pairing nanoparticles effects on photodynamic therapy of MDA-MB-231 breast cancer cell.

    Science.gov (United States)

    Hosseinzadeh, Reza; Khorsandi, Khatereh

    2017-06-01

    The aim of current study was to use methylene blue-curcumin ion pair nanoparticles and single dyes as photosensitizer for comparison of photodynamic therapy (PDT) efficacy on MDA-MB-231 cancer cells, also various light sources effect on activation of photosensitizer (PS) was considered. Ion pair nanoparticles were synthesized using opposite charge ions precipitation and lyophilized. The PDT experiments were designed and the effect of PSs and light sources (Red LED (630nm; power density: 30mWcm(-2)) and blue LED (465nm; power density: 34mWcm(-2))) on the human breast cancer cell line were examined. The effect of PS concentration (0-75μg.mL(-1)), incubation time, irradiation time and light sources, and priority in irradiation of blue or red lights were determined. The results show that the ion pairing of methylene blue and curcumin enhance the photodynamic activity of both dyes and the cytotoxicity of ion pair nanoparticles on the MDA-231 breast cancer cell line. Blue and red LED light sources were used for photo activation of photosensitizers. The results demonstrated that both dyes can activate using red light LED better than blue light LED for singlet oxygen producing. Nano scale ion pair precipitating of methylene blue-curcumin enhanced the cell penetrating and subsequently cytotoxicity of both dyes together. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Khat promotes human breast cancer MDA-MB-231 cell apoptosis via mitochondria and MAPK-associated pathways.

    Science.gov (United States)

    Lu, Yu; Li, Yanyan; Xiang, Min; Zhou, Jie; Chen, Juan

    2017-10-01

    Khat (Catha edulis Forsk) is a flowering evergreen plant in Eastern Africa and Southwestern Arabia. Consumption of Khat has been associated with the development of oral cancer, but its mechanism of action on the molecular level remains unclear. The present study demonstrated the cytotoxic effect of khat extracts on the human breast cancer cell line MDA-MB-231. Trypan blue exclusion assays, flow cytometry, fluorescent and electron microscopy, as well as western blotting were used to analyze the effects of Khat on the cell viability of breast cancer cells, expression of apoptotic-associated proteins and the levels of reactive oxygen species (ROS). The results of the present study demonstrated that treatment with 400 µg/ml khat was able to induce cell death in breast cancers, with an increase in the protein expression of apoptosis regulator Bax and a decrease in the expression of B-cell lymphoma 2, along with a decrease in ROS levels in a time-dependent manner. Furthermore, the expression of activated c-Jun N-terminal and extracellular regulated protein kinases was increased in khat-treated cells compared with untreated cells. Mitochondria participated in cell apoptosis through the release of apoptogenic proteins to the cytosol and the generation of excess reactive oxygen species. The results of the present study suggest that khat induces MDA-MB-231 cell apoptosis via MAPK activation and mitochondrial-mediated death.

  11. 2q23.1 microdeletion identified by array comparative genomic hybridisation: an emerging phenotype with Angelman-like features?

    Science.gov (United States)

    Jaillard, S; Dubourg, C; Gérard-Blanluet, M; Delahaye, A; Pasquier, L; Dupont, C; Henry, C; Tabet, A-C; Lucas, J; Aboura, A; David, V; Benzacken, B; Odent, S; Pipiras, E

    2009-12-01

    Genome-wide screening of patients with mental retardation using array comparative genomic hybridisation (CGH) has identified several novel imbalances. With this genotype-first approach, the 2q22.3q23.3 deletion was recently described as a novel microdeletion syndrome. The authors report two unrelated patients with a de novo interstitial deletion mapping in this genomic region and presenting similar "pseudo-Angelman" phenotypes, including severe psychomotor retardation, speech impairment, epilepsy, microcephaly, ataxia, and behavioural disabilities. The microdeletions were identified by array CGH using oligonucleotide and bacterial artificial chromosome (BAC) arrays, and further confirmed by fluorescence in situ hybridisation (FISH) and semi-quantitative polymerase chain reaction (PCR). The boundaries and sizes of the deletions in the two patients were different but an overlapping region of about 250 kb was defined, which mapped to 2q23.1 and included two genes: MBD5 and EPC2. The SIP1 gene associated with the Mowat-Wilson syndrome was not included in the deleted genomic region. Haploinsufficiency of one of the deleted genes (MBD5 or EPC2) could be responsible for the common clinical features observed in the 2q23.1 microdeletion syndrome, and this hypothesis needs further investigation.

  12. FGFR4 GLY388 isotype suppresses motility of MDA-MB-231 breast cancer cells by EDG-2 gene repression.

    Science.gov (United States)

    Stadler, Christiane Regina; Knyazev, Pjotr; Bange, Johannes; Ullrich, Axel

    2006-06-01

    Clinical investigations of an FGFR4 germline polymorphism, resulting in substitution of glycine by arginine at codon 388 (G388 to R388), have shown a correlation between FGFR4 R388 and aggressive disease progression in cancer patients. Here, we studied the differential effects of the two FGFR4 isotypes on cellular signalling and motility in the MDA-MB-231 human breast cancer cell model. cDNA array analysis showed the ability of FGFR4 G388 to suppress expression of specific genes involved in invasiveness and motility. Further investigations concentrating on cell signalling and motility revealed an abrogation of phosphatidylinositol-3-kinase-dependent LPA-induced Akt activation and cell migration due to downregulation of the LPA receptor Edg-2 in FGFR4 G388-expressing MDA-MB-231 cells. Moreover, FGFR4 G388 expression attenuated the invasivity of the breast cancer cell line and decreased small Rho GTPase activity. We conclude that FGFR4 G388 suppresses cell motility of invasive breast cancer cells by altering signalling pathways and the expression of genes that are required for metastasis. Therefore, the positive effect of FGFR4 R388 on disease progression appears to result from a loss of the tumour suppressor activity displayed by FGFR4 G388 rather than the acquisition or enhancement of oncogenic potential.

  13. Evaluation of the cytotoxic activity of Hypericum spp. on human glioblastoma A1235 and breast cancer MDA MB-231 cells.

    Science.gov (United States)

    Madunić, Josip; Matulić, Maja; Friščić, Maja; Pilepić, Kroata Hazler

    2016-11-01

    Cytotoxic activity of 16 Hypericum ethanolic extracts was evaluated by MTT assay on two human cancer cell lines: glioblastoma A1235 and breast cancer MDA MB-231. Morphology and the type of induced cell death were determined using light and fluorescence microscopy. The majority of Hypericum extracts had no significant cytotoxic effect on MDA MB-231 cells. Eight extracts exhibited mild cytotoxic effect on A1235 cells after 24 h incubation, ranging from 8.0% (H. patulum) to 21.7% (H. oblongifolium). After 72 h of treatment, the strongest inhibition of A1235 viability was observed for extracts of H. androsaemum (26.4-43.9%), H. balearicum (25.8-36.3%), H. delphicum (14.8-27.4%) and H. densiflorum (11.2-24.1%). Micro-scopic examination of cells showed apoptosis as the dominant type of cell death. Due to observed high viability of treated cells, we propose that cytotoxic effects of Hypericum extracts could be related to alternations/interruptions in the cell cycle.

  14. MK886 inhibits the pioglitazone-induced anti-invasion of MDA-MB-231 cells is associated with PPARα/γ, FGF4 and 5LOX.

    Science.gov (United States)

    Nadarajan, Kalpanah; Balaram, Prabha; Khoo, Boon Yin

    2016-10-01

    The goal of this study was to determine the effects of PGZ and MK886 on the mRNA expression of PPARα and other associated genes in MDA-MB-231 cells, and the biological mechanisms induced by both drugs were also assessed. The levels of PPARα mRNA expression in PGZ-treated and MK886-treated MDA-MB-231 cells were determined using real-time PCR; the growth inhibitory effects of PGZ and MK886 were determined using the trypan blue exclusion assay; the induction of apoptosis by PGZ and MK886 was determined using DNA fragmentation assay and real-time PCR; and the invasion of PGZ-treated and MK886-treated MDA-MB-231 cells was determined using the wound healing and transwell migration assays. In addition, we correlated the expression of PPARα mRNA with other genes, including PPARγ, FGF4 and 5LOX, in drug-treated MDA-MB-231 cells. Our results demonstrated that the treatment of MDA-MB-231 cells with PGZ increased the expression of PPARα/γ mRNA and that this expression could be inhibited by treatment with MK886. Both drugs reduced the viability of MDA-MB-231 cells independently of PPARα/γ mRNA expression but did not induce apoptosis. The wound caused by invasion was not healed by PGZ-treated MDA-MB-231 cells, but it was healed by MK886-treated cancer cells, indicating that the reduction of invasion in PGZ-treated MDA-MB-231 cells was eliminated by treatment with MK886, and this finding was validated by the transwell migration assay. This phenomenon might also be associated with the expression of PPARα/γ, FGF4 and 5LOX mRNA in the treated cancer cells. This study provides useful information regarding the mRNA expression levels of PPARα and other related genes in MDA-MB-231 cells. These genes could be attractive targets for reducing the invasion of breast cancer.

  15. 姜黄素对乳腺癌MDA-MB-231细胞株放射增敏作用的研究%Effect of curcumin on radiosensitization of breast cancer cell MDA-MB-231

    Institute of Scientific and Technical Information of China (English)

    李峰; 王辉; 牛国梁; 张树友; 谢荣俊; 周明利

    2013-01-01

    目的 姜黄素(curcumin)能有效增强放射线对乳腺癌的作用,但其作用机制尚不明朗.该文探讨姜黄素对人乳腺癌MDA-MB-231细胞放射增敏的作用机制.方法 对数生长的乳腺癌MDA-MB-231细胞,分成对照组、姜黄素组、照射组及联合组,使用流式细胞术(flow cytometry,FCM)检测细胞凋亡率;克隆形成实验检测放射增敏作用;蛋白免疫印迹法(Western blotting)检测Akt及pAkt蛋白表达.结果 联合组凋亡率显著高于照射组[(28.49±4.66)% vs(12.41±4.98)%](q=20.07,P<0.01);与照射组比较,克隆形成实验的放射敏感性指标标准阈剂量(Dq)、平均致死剂量(Do)、2 Gy存活分数(SF2)均明显降低,放射增敏比(SERDO)为1.293;各组间的Akt蛋白差异没有统计学意义(F=3.467,P=0.051),与对照组比较,单纯照射能提高pAkt的蛋白表达(q =4.71,P<0.05),而姜黄素可以抑制pAkt蛋白的表达(q =4.11,P<0.05),两者联用后pAkt蛋白表达较单纯照射组显著降低(q =7.36,P<0.01).结论 姜黄素可以增强射线对乳腺癌MDA-MB-231细胞的敏感性,其机制可能与姜黄素阻断PI3K/Akt信号通路中Akt磷酸化有关.

  16. The Cerebro-oculo-facio-skeletal Syndrome Point Mutation F231L in the ERCC1 DNA Repair Protein Causes Dissociation of the ERCC1-XPF Complex*

    Science.gov (United States)

    Faridounnia, Maryam; Wienk, Hans; Kovačič, Lidija; Folkers, Gert E.; Jaspers, Nicolaas G. J.; Kaptein, Robert; Hoeijmakers, Jan H. J.; Boelens, Rolf

    2015-01-01

    The ERCC1-XPF heterodimer, a structure-specific DNA endonuclease, is best known for its function in the nucleotide excision repair (NER) pathway. The ERCC1 point mutation F231L, located at the hydrophobic interaction interface of ERCC1 (excision repair cross-complementation group 1) and XPF (xeroderma pigmentosum complementation group F), leads to severe NER pathway deficiencies. Here, we analyze biophysical properties and report the NMR structure of the complex of the C-terminal tandem helix-hairpin-helix domains of ERCC1-XPF that contains this mutation. The structures of wild type and the F231L mutant are very similar. The F231L mutation results in only a small disturbance of the ERCC1-XPF interface, where, in contrast to Phe231, Leu231 lacks interactions stabilizing the ERCC1-XPF complex. One of the two anchor points is severely distorted, and this results in a more dynamic complex, causing reduced stability and an increased dissociation rate of the mutant complex as compared with wild type. These data provide a biophysical explanation for the severe NER deficiencies caused by this mutation. PMID:26085086

  17. BETULINIC ACID WAS MORE CYTOTOXIC TOWARDS THE HUMAN BREAST CANCER CELL LINE MDA-MB-231 THAN THE HUMAN PROMYELOCYTIC LEUKAEMIA CELL LINE HL-60

    Directory of Open Access Journals (Sweden)

    LATIFAH SAIFUL YAZAN

    2009-01-01

    Full Text Available Betulinic acid (BA is a pentacyclic triterpene found in several botanical sources that has been shown to cause apoptosis in a number of cell lines. This study was undertaken to determine the in vitro cytotoxic properties of BA towards the human mammary carcinoma cell line MDA-MB-231 and the human promyelocytic leukaemia cell line HL-60 and the mode of the induced cell death. The cytotoxicity and mode of cell death of BA were determined using the MTT assay and DNAfragmentation analysis, respectively. In our study, the compound was found to be cytotoxic to MDA-MB-231 and HL-60 cells with IC50 values of 58 μg/mL and 134 μg/mL, respectively. Cells treated with high concentrations of BA exhibited features characteristic of apoptosis such as blebbing, shrinking and a number of small cytoplasm body masses when viewed under an inverted light microscope after 24 h. The incidence of apoptosis in MDA-MB-231 was further confirmed bythe DNA fragmentation analysis, with the formation of DNA fragments of oligonucleosomal size (180-200 base pairs, giving a ladder-like pattern on agarose gel electrophoresis. BA was more cytotoxic towards MDA-MB-231 than HL-60 cells, and induced apoptosis in MDA-MB-231 cells.

  18. Peripheral-type benzodiazepine receptor levels correlate with the ability of human breast cancer MDA-MB-231 cell line to grow in SCID mice.

    Science.gov (United States)

    Hardwick, M; Rone, J; Han, Z; Haddad, B; Papadopoulos, V

    2001-11-01

    MDA-MB-231 (MDA-231) human breast cancer cells have a high proliferation rate, lack the estrogen receptor, express the intermediate filament vimentin, the hyaluronan receptor CD44, and are able to form tumors in nude mice. The MDA-231 cell line has been used in our laboratory to examine the role of the peripheral-type benzodiazepine receptor (PBR) in the progression of cancer. During these studies 2 populations of MDA-231 cells were subcloned based on the levels of PBR. The subclones proliferated at approximately the same rate, lacked the estrogen receptor, expressed vimentin and CD44, and had the same in vitro chemoinvasive and chemotactic potential. Both restriction fragment length polymorphism and comparative genomic hybridization analyses of genomic DNA from these cells indicated that both subclones are of the same genetic lineage. Only the subclone with high PBR levels, however, was able to form tumors when injected in SCID mice. These data suggest that the ability of MDA-231 cells to form tumors in vivo may depend on the amount of PBR present in the cells.

  19. The Cerebro-oculo-facio-skeletal Syndrome Point Mutation F231L in the ERCC1 DNA Repair Protein Causes Dissociation of the ERCC1-XPF Complex.

    Science.gov (United States)

    Faridounnia, Maryam; Wienk, Hans; Kovačič, Lidija; Folkers, Gert E; Jaspers, Nicolaas G J; Kaptein, Robert; Hoeijmakers, Jan H J; Boelens, Rolf

    2015-08-14

    The ERCC1-XPF heterodimer, a structure-specific DNA endonuclease, is best known for its function in the nucleotide excision repair (NER) pathway. The ERCC1 point mutation F231L, located at the hydrophobic interaction interface of ERCC1 (excision repair cross-complementation group 1) and XPF (xeroderma pigmentosum complementation group F), leads to severe NER pathway deficiencies. Here, we analyze biophysical properties and report the NMR structure of the complex of the C-terminal tandem helix-hairpin-helix domains of ERCC1-XPF that contains this mutation. The structures of wild type and the F231L mutant are very similar. The F231L mutation results in only a small disturbance of the ERCC1-XPF interface, where, in contrast to Phe(231), Leu(231) lacks interactions stabilizing the ERCC1-XPF complex. One of the two anchor points is severely distorted, and this results in a more dynamic complex, causing reduced stability and an increased dissociation rate of the mutant complex as compared with wild type. These data provide a biophysical explanation for the severe NER deficiencies caused by this mutation.

  20. Inhibition effect of luteolin on IL-8 signal path in breast cancer cells MDA MB 231%Luteolin抑制乳腺癌细胞MDA-MB231增殖及IL-8信号通路的实验研究

    Institute of Scientific and Technical Information of China (English)

    李文仿; 周科; 赵宗彬; 王明华; 王耕

    2014-01-01

    目的:探讨木犀草素(Luteolin)对乳腺癌细胞MDA-MB231增殖及IL-8信号通路的抑制作用.方法:采用不同浓度的Luteolin处理乳腺癌细胞MDA-MB231,观察MDA-MB231细胞的增殖、IL-8蛋白和mRNA的表达以及AKT、ERK的表达.结果:Luteolin可抑制MDA-MB231细胞的增殖和IL-8的分泌,并明显抑制IL-8对乳腺癌细胞的激活.结论:Luteolin是重要的乳腺癌抑制剂,在预防乳腺癌复发及转移中可能有重要的作用.

  1. Herbal Extract SH003 Suppresses Tumor Growth and Metastasis of MDA-MB-231 Breast Cancer Cells by Inhibiting STAT3-IL-6 Signaling

    Directory of Open Access Journals (Sweden)

    Youn Kyung Choi

    2014-01-01

    Full Text Available Cancer inflammation promotes cancer progression, resulting in a high risk of cancer. Here, we demonstrate that our new herbal extract, SH003, suppresses both tumor growth and metastasis of MDA-MB-231 breast cancer cells via inhibiting STAT3-IL-6 signaling path. Our new herbal formula, SH003, mixed extract from Astragalus membranaceus, Angelica gigas, and Trichosanthes kirilowii Maximowicz, suppressed MDA-MB-231 tumor growth and lung metastasis in vivo and reduced the viability and metastatic abilities of MDA-MB-231 cells in vitro. Furthermore, SH003 inhibited STAT3 activation, which resulted in a reduction of IL-6 production. Therefore, we conclude that SH003 suppresses highly metastatic breast cancer growth and metastasis by inhibiting STAT3-IL-6 signaling path.

  2. Assessment of the anti-metastatic properties of sanguiin H-6 in HUVECs and MDA-MB-231 human breast cancer cells.

    Science.gov (United States)

    Park, Eun-Hwa; Park, Jun Yeon; Yoo, Hwa-Seung; Yoo, Jeong-Eun; Lee, Hye Lim

    2016-07-15

    The anti-metastatic properties of sanguiin H-6 were examined in human umbilical vein vascular endothelial cells (HUVECs) and MDA-MB-231 human breast cancer cells. In HUVECs, sanguiin H-6 inhibited the density of migrated cells compared to that observed after treatment with the vehicle. In addition, sanguiin H-6 at a concentration of 6.25μM significantly blocked tube formation. Treatment with up to 25μM sanguiin H-6 had no effect on MDA-MB-231 cells, whereas treatment with 200μM sanguiin H-6 decreased cell viability. Sanguiin H-6 significantly decreased the expression levels of vascular endothelial growth factor (VEGF), phosphorylated Akt, and extracellular signal-regulated kinase 1/2 (ERK1/2) in MDA-MB-231 cells. These findings suggest that sanguiin H-6 is potentially useful as an anti-metastatic agent.

  3. Anticancer activity of a monobenzyltin complex C1 against MDA-MB-231 cells through induction of Apoptosis and inhibition of breast cancer stem cells

    Science.gov (United States)

    Fani, Somayeh; Kamalidehghan, Behnam; Lo, Kong Mun; Nigjeh, Siamak Ebrahimi; Keong, Yeap Swee; Dehghan, Firouzeh; Soori, Rahman; Abdulla, Mahmood Ameen; Chow, Kit May; Ali, Hapipah Mohd; Hajiaghaalipour, Fatemeh; Rouhollahi, Elham; Hashim, Najihah Mohd

    2016-01-01

    In the present study, we examined the cytotoxic effects of Schiff base complex, [N-(3,5-dichloro-2-oxidobenzylidene)-4-chlorobenzyhydrazidato](o-methylbenzyl)aquatin(IV) chloride, and C1 on MDA-MB-231 cells and derived breast cancer stem cells from MDA-MB-231 cells. The acute toxicity experiment with compound C1 revealed no cytotoxic effects on rats. Fluorescent microscopic studies using Acridine Orange/Propidium Iodide (AO/PI) staining and flow cytometric analysis using an Annexin V probe confirmed the occurrence of apoptosis in C1-treated MDA-MB-231 cells. Compound C1 triggered intracellular reactive oxygen species (ROS) production and lactate dehydrogenase (LDH) releases in treated MDA-MB-231 cells. The Cellomics High Content Screening (HCS) analysis showed the induction of intrinsic pathways in treated MDA-MB-231 cells, and a luminescence assay revealed significant increases in caspase 9 and 3/7 activity. Furthermore, flow cytometric analysis showed that compound C1 induced G0/G1 arrest in treated MDA-MB-231 cells. Real time PCR and western blot analysis revealed the upregulation of the Bax protein and the downregulation of the Bcl-2 and HSP70 proteins. Additionally, this study revealed the suppressive effect of compound C1 against breast CSCs and its ability to inhibit the Wnt/β-catenin signaling pathways. Our results demonstrate the chemotherapeutic properties of compound C1 against breast cancer cells and derived breast cancer stem cells, suggesting that the anticancer capabilities of this compound should be clinically assessed. PMID:27976692

  4. Inhibition of ROS production, autophagy or apoptosis signaling reversed the anticancer properties of Antrodia salmonea in triple-negative breast cancer (MDA-MB-231) cells.

    Science.gov (United States)

    Chang, Chia-Ting; Korivi, Mallikarjuna; Huang, Hui-Chi; Thiyagarajan, Varadharajan; Lin, Kai-Yuan; Huang, Pei-Jane; Liu, Jer-Yuh; Hseu, You-Cheng; Yang, Hsin-Ling

    2017-05-01

    We investigated the in vitro and in vivo anticancer properties of Antrodia salmonea (AS), a well-known edible/medicinal mushroom in Taiwan, on human triple-negative breast cancer (MDA-MB-231) cells and xenografted nude mice; and revealed the underlying molecular mechanisms involved in autophagic- and apoptotic-cell death. Treatment of MDA-MB-231 cells with fermented culture broth of AS (0-200 μg/mL) inhibited cell viability/growth. AS-induced autophagy was evidenced via increased LC3-II accumulation, GFP-LC3 puncta and AVOs formation in MDA-MB-231 cells. These events are associated with increased ATG7, decreased p-mTOR, vanished SQSTM1/p62 expressions and dysregulated Beclin-1/Bcl-2 ratio. AS-induced apoptosis/necrosis through increased DNA fragmentation, Annexin-V/PI stained cells and Bax expression. Both mitochondrial (caspase-9/caspase-3/PARP) and death-receptor (caspase-8/FasL/Fas) signaling pathways are involved in execution of apoptosis. Interestingly, blockade of AS-induced ROS production by N-acetylcysteine pretreatment substantially attenuated AS-induced autophagy, mitochondrial dysfunction and autophagic/apoptotic-cell death. Inhibition of apoptosis by Z-VAD-FMK suppressed AS-induced autophagic-death (decreased LC3-II/AVOs). Similarly, inhibition of autophagy by 3-methyladenine/chloroquine diminished AS-induced apoptosis (decreased DNA fragmentation/caspase-3) in MDA-MB-231 cells. Bioluminescence imaging further confirmed that AS inhibited breast tumor growth in living MDA-MB-231-luciferase-injected nude mice. Taken together, AS crucially involved in execution/propagation of autophagic- or apoptotic-death of MDA-MB-231 cells, and decreased tumor growth in xenografted nude mice. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Anticancer activity of a monobenzyltin complex C1 against MDA-MB-231 cells through induction of Apoptosis and inhibition of breast cancer stem cells.

    Science.gov (United States)

    Fani, Somayeh; Kamalidehghan, Behnam; Lo, Kong Mun; Nigjeh, Siamak Ebrahimi; Keong, Yeap Swee; Dehghan, Firouzeh; Soori, Rahman; Abdulla, Mahmood Ameen; Chow, Kit May; Ali, Hapipah Mohd; Hajiaghaalipour, Fatemeh; Rouhollahi, Elham; Hashim, Najihah Mohd

    2016-12-15

    In the present study, we examined the cytotoxic effects of Schiff base complex, [N-(3,5-dichloro-2-oxidobenzylidene)-4-chlorobenzyhydrazidato](o-methylbenzyl)aquatin(IV) chloride, and C1 on MDA-MB-231 cells and derived breast cancer stem cells from MDA-MB-231 cells. The acute toxicity experiment with compound C1 revealed no cytotoxic effects on rats. Fluorescent microscopic studies using Acridine Orange/Propidium Iodide (AO/PI) staining and flow cytometric analysis using an Annexin V probe confirmed the occurrence of apoptosis in C1-treated MDA-MB-231 cells. Compound C1 triggered intracellular reactive oxygen species (ROS) production and lactate dehydrogenase (LDH) releases in treated MDA-MB-231 cells. The Cellomics High Content Screening (HCS) analysis showed the induction of intrinsic pathways in treated MDA-MB-231 cells, and a luminescence assay revealed significant increases in caspase 9 and 3/7 activity. Furthermore, flow cytometric analysis showed that compound C1 induced G0/G1 arrest in treated MDA-MB-231 cells. Real time PCR and western blot analysis revealed the upregulation of the Bax protein and the downregulation of the Bcl-2 and HSP70 proteins. Additionally, this study revealed the suppressive effect of compound C1 against breast CSCs and its ability to inhibit the Wnt/β-catenin signaling pathways. Our results demonstrate the chemotherapeutic properties of compound C1 against breast cancer cells and derived breast cancer stem cells, suggesting that the anticancer capabilities of this compound should be clinically assessed.

  6. Pentamidine reduces expression of hypoxia-inducible factor-1α in DU145 and MDA-MB-231 cancer cells.

    Science.gov (United States)

    Jung, Hui-Jung; Suh, Seong-Il; Suh, Min-Ho; Baek, Won-Ki; Park, Jong-Wook

    2011-04-01

    Pentamidine is an aromatic diamine used for the treatment of human protozoa infections. Recently, pentamidine has been reported to exhibit anticancer properties. In this study, we report that pentamidine inhibits expression of hypoxia-inducible factor (HIF)-1α in cancer cells. Pentamidine decreased HIF-1α protein translation and enhanced its protein degradation in DU145 prostate cancer and MDA-MB-231 breast cancer cells. In parallel with reduction of de novo synthesis of HIF-1α, pentamidine was able to suppress global protein translation, an effect accompanied by the reduction of eIF4F complex formation and also the induction of eIF2α phosphorylation. These results show that pentamidine is a potential inhibitor of HIF-1α and its potential as a cancer therapeutic reagent warrants further study.

  7. Evaluation of anticancer potential of Bacopa monnieri L. against MCF-7 and MDA-MB 231 cell line

    Directory of Open Access Journals (Sweden)

    Md. Nasar Mallick

    2015-01-01

    Full Text Available Background: The ethanolic extract of Bacopa monnieri contains bacoside A and B, brahmin, cucurbitacins, and betulinic acid. Currently, cucurbitacins have also been reported for their strong anti-tumorigenic and anti-proliferative activity by inducing cell cycle arrest at the G2/M phase and formation of multiplied cells. The present study was carried out to evaluate the in vitro cytotoxic activity of ethanolic extract of dichloromethane (DCM fraction of B. monnieri on two different cell lines. Materials and Methods: The ethanolic extract of B. monnieri was prepared using soxhlet extraction method and different fractions (hexane, DCM, methanol, acetone, and water of ethanolic extracts were prepared. The 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay of ethanolic extract and of all fractions was carried out on MCF-7 and MDA-MB 231 cell lines. The presence of cucurbitacins and betulinic acid in these fractions was confirmed by high-performance thin layer chromatography. Results: The IC50 values of ethanolic extract of B. monnieri in MCF-7 and MDA-MB 231 cell lines were 72.0 μg/mL and 75.0 μg/mL, respectively. The DCM fraction of B. monnieri showed maximum cytotoxic activity among all fraction upto 72 h and was found to be 57.0 μg/mL and 42.0 μg/mL, respectively. Conclusion: The results showed good cytotoxic activity in DCM fraction in both the cell lines may be due to the presence of cucurbitacins and betulinic acid in DCM fraction.

  8. Berberine hydrochloride IL-8 dependently inhibits invasion and IL-8-independently promotes cell apoptosis in MDA-MB-231 cells.

    Science.gov (United States)

    Li, Xiang; Zhao, Shu-Juan; Shi, Hai-Lian; Qiu, Shui-Ping; Xie, Jian-Qun; Wu, Hui; Zhang, Bei-Bei; Wang, Zheng-Tao; Yuan, Jian-Ye; Wu, Xiao-Jun

    2014-12-01

    Breast cancer, the leading cause of cancer-related mortality worldwide in females, has high metastastic and recurrence rates. The aim of the present study was to evaluate the anti-metastatic and anticancer in situ effect of berberine hydrochloride (BER) in MDA-MB-231 cells. BER dose-dependently inhibited proliferation and the IL-8 secretion of MDA-MB-231 cells. Additional experiments revealed that the inactivation of PI3K, JAK2, NF-κB and AP-1 by BER contributed to the decreased IL-8 secretion. BER abrogated cell invasion induced by IL-8 accompanied with the downregulation of the gene expression of MMP-2, EGF, E-cadherin, bFGF and fibronectin. In addition, BER reduced cell motility but induced G2/M arrest and cell apoptosis in an IL-8‑independent manner. BER modulated multiple signaling pathway molecules involved in the regulation of cell apoptosis, including activation of p38 MAPK and JNK and deactivation of JAK2, p85 PI3K, Akt and NF-κB. The enhanced cell apoptosis induced by BER was eliminated by inhibitors of p38 MAPK and JNK but was strengthened by activator of p38 MAPK. Thus, BER inhibited cell metastasis partly through the IL-8 mediated pathway while it induced G2/M arrest and promoted cell apoptosis through the IL-8 independent pathway. Apoptosis induced by BER was mediated by crosstalks of various pathways including activation of p38 MAPK and JNK pathways and inactivation of Jak2/PI3K/NF-κB/AP-1 pathways. The results suggested that BER may be an efficient and safe drug candidate for treating highly metastatic breast cancer.

  9. Activity of plasma membrane V-ATPases is critical for the invasion of MDA-MB231 breast cancer cells.

    Science.gov (United States)

    Cotter, Kristina; Capecci, Joseph; Sennoune, Souad; Huss, Markus; Maier, Martin; Martinez-Zaguilan, Raul; Forgac, Michael

    2015-02-06

    The vacuolar (H(+))-ATPases (V-ATPases) are a family of ATP-driven proton pumps that couple ATP hydrolysis with translocation of protons across membranes. Previous studies have implicated V-ATPases in cancer cell invasion. It has been proposed that V-ATPases participate in invasion by localizing to the plasma membrane and causing acidification of the extracellular space. To test this hypothesis, we utilized two separate approaches to specifically inhibit plasma membrane V-ATPases. First, we stably transfected highly invasive MDA-MB231 cells with a V5-tagged construct of the membrane-embedded c subunit of the V-ATPase, allowing for extracellular expression of the V5 epitope. We evaluated the effect of addition of a monoclonal antibody directed against the V5 epitope on both V-ATPase-mediated proton translocation across the plasma membrane and invasion using an in vitro Matrigel assay. The addition of anti-V5 antibody resulted in acidification of the cytosol and a decrease in V-ATPase-dependent proton flux across the plasma membrane in transfected but not control (untransfected) cells. These results demonstrate that the anti-V5 antibody inhibits activity of plasma membrane V-ATPases in transfected cells. Addition of the anti-V5 antibody also inhibited in vitro invasion of transfected (but not untransfected) cells. Second, we utilized a biotin-conjugated form of the specific V-ATPase inhibitor bafilomycin. When bound to streptavidin, this compound cannot cross the plasma membrane. Addition of this compound to MDA-MB231 cells also inhibited in vitro invasion. These studies suggest that plasma membrane V-ATPases play an important role in invasion of breast cancer cells.

  10. Parthenolide induces superoxide anion production by stimulating EGF receptor in MDA-MB-231 breast cancer cells.

    Science.gov (United States)

    D'Anneo, A; Carlisi, D; Emanuele, S; Buttitta, G; Di Fiore, R; Vento, R; Tesoriere, G; Lauricella, M

    2013-12-01

    The sesquiterpene lactone parthenolide (PN) has recently attracted considerable attention because of its anti-microbial, anti-inflammatory and anticancer effects. However, the mechanism of its cytotoxic action on tumor cells remains scarcely defined. We recently provided evidence that the effect exerted by PN in MDA-MB-231 breast cancer cells was mediated by the production of reactive oxygen species (ROS). The present study shows that PN promoted the phosphorylation of EGF receptor (phospho-EGFR) at Tyr1173, an event which was observed already at 1 h of incubation with 25 µM PN and reached a peak at 8-16 h. This effect seemed to be a consequence of ROS production, because N-acetylcysteine (NAC), a powerful ROS scavenger, prevented the increment of phospho-EGFR levels. In addition fluorescence analyses performed using dihydroethidium demonstrated that PN stimulated the production of superoxide anion already at 2-3 h of incubation and the effect further increased prolonging the time of treatment, reaching a peak at 8-16 h. Superoxide anion production was markedly hampered by apocynin, a well known NADPH oxidase (NOX) inhibitor, suggesting that the effect was dependent on NOX activity. The finding that AG1478, an EGFR kinase inhibitor, substantially blocked both EGFR phosphorylation and superoxide anion production strongly suggested that phosphorylation of EGFR can be responsible for the activation of NOX with the consequent production of superoxide anion. Therefore, EGFR phosphorylation can exert a key role in the production of superoxide anion and ROS induced by PN in MDA-MB-231 cells.

  11. Progesterone induces cellular differentiation in MDA-MB-231 breast cancer cells transfected with progesterone receptor complementary DNA.

    Science.gov (United States)

    Lin, Valerie Chun-Ling; Jin, Rongxian; Tan, Puay-Hoon; Aw, Swee-Eng; Woon, Chow-Thai; Bay, Boon-Huat

    2003-06-01

    Progesterone is an important regulator of growth and differentiation in breast tissues. In this study, the effect of progesterone on cell differentiation was evaluated in the estrogen receptor-negative and progesterone receptor (PR)-negative MDA-MB-231 cell line which was transfected with PR-complementary DNA. Morphological changes were analyzed at the ultrastructural level by scanning and transmission electron microscopy. Progesterone-treated PR-transfected cells exhibited a more protracted and well spread morphology with an increase in organelles such as mitochondria and rough endoplasmic reticulum as compared to the rounded form of control vehicle (0.1% ethanol)-treated PR-transfected cells. Vehicle and progesterone-treated MDA-MB-231 cells transfected with the pSG5 plasmid (transfection control cells) had similar rounded morphology as control vehicle-treated PR-transfected cells. Immunofluorescence staining revealed that expression of E-cadherin, a differentiation marker, was more prominent in progesterone-treated cells. Expression of keratin and vimentin but not beta-catenin was up-regulated in progesterone treated cells when evaluated by immunoblotting. As signal transducers and activators of transcription (STAT) molecules have been implicated in mammary differentiation, we analyzed the expression of Stat 1, 3, 5a, and 5b proteins and found a significant up-regulation of the Stat 5b protein in progesterone-treated cells. We have provided in vitro evidence of the close association of PR with differentiation in breast cancer. It is likely that the Stat 5b protein may play a major role in progesterone-induced differentiation in breast cancer cells.

  12. Modulation of markers associated with aggressive phenotype in MDA-MB-231 breast carcinoma cells by sulforaphane.

    Science.gov (United States)

    Hunakova, L; Sedlakova, O; Cholujova, D; Gronesova, P; Duraj, J; Sedlak, J

    2009-01-01

    Metastasis as a complex process involves loss of adhesion, migration, invasion and proliferation of cancer cells. Sulforaphane (SFN) is one of naturally occurring cancer chemopreventive isothiocyanates found in cruciferous vegetables, consumption of which has been associated with reduced risk of cancer. In this study, we describe effect of SFN on various aspects determining invasive behavior of MDA-MB-231 human breast carcinoma cells. We studied modulation of molecules associated with epithelial to mesenchymal transition (EMT), hypoxic marker CA IX and mitochondrially located peripheral benzodiazepine receptor (PBR) using flow cytometry, gene expression of matrix metalloproteinases MMP1, 3, 7, 9, 14, transcription factors POU5F1 and Twist1 mRNA by RT PCR, and cytokine production by multiplex bead assay. SFN downregulated PBR and vimentin expression in a dose dependent manner, but significantly affected neither HIF-1alpha, nor CA IX protein expression, nor VEGF and GLUT1 mRNA levels. Among studied MMPs, MMP7 and MMP14 mRNA were downregulated while no apparent effect on MMP1, MMP3 and MMP9 was observed. Further, we found significant down regulation of Twist1 and POU5F1, transcription factors that mediate EMT and the self-renewal of undifferentiated embryonic stem cells. SFN reduced also the production of pro-inflammatory cytokines IL-1beta, IL-6, TNF-alpha, IFN-gamma, immunomodulating cytokine IL-4 and growth factors involved in angiogenesis PDGF and VEGF. Our study shows that SFN efficacy is associated with the reversal of several biological characteristics connected with EMT or implicated in the matrix degradation and extracellular proteolysis, as well as with reduced production of pro-inflammatory cytokines and pro-angiogenic growth factors in MDA-MB-231 cells.

  13. Evidence for active galactic nucleus feedback in the broad absorption lines and reddening of MRK 231 {sup ,}

    Energy Technology Data Exchange (ETDEWEB)

    Leighly, Karen M.; Baron, Eddie; Lucy, Adrian B. [Homer L. Dodge Department of Physics and Astronomy, The University of Oklahoma, 440 West Brooks Street, Norman, OK 73019 (United States); Terndrup, Donald M. [Department of Astronomy, The Ohio State University, 140 West 18th Avenue, Columbus, OH 43210 (United States); Dietrich, Matthias [Department of Physics and Astronomy, Ohio University, Clippinger Labs 251B, Athens, OH 45701 (United States); Gallagher, Sarah C. [Department of Physics and Astronomy, The University of Western Ontario, London, ON, N6A 3K7 (Canada)

    2014-06-20

    We present the first J-band spectrum of Mrk 231, which reveals a large He I* λ10830 broad absorption line with a profile similar to that of the well-known Na I broad absorption line. Combining this spectrum with optical and UV spectra from the literature, we show that the unusual reddening noted by Veilleux et al. is explained by a reddening curve like those previously used to explain low values of total-to-selective extinction in Type Ia supernovae. The nuclear starburst may be the origin and location of the dust. Spatially resolved emission in the broad absorption line trough suggests nearly full coverage of the continuum emission region. The broad absorption lines reveal higher velocities in the He I* lines (produced in the quasar-photoionized H II region) compared with the Na I and Ca II lines (produced in the corresponding partially ionized zone). Cloudy simulations show that a density increase is required between the H II and partially ionized zones to produce ionic column densities consistent with the optical and IR absorption line measurements and limits, and that the absorber lies ∼100 pc from the central engine. These results suggest that the He I* lines are produced in an ordinary quasar BAL wind that impacts upon, compresses, and accelerates the nuclear starburst's dusty effluent (feedback in action), and the Ca II and Na I lines are produced in this dusty accelerated gas. This unusual circumstance explains the rarity of Na I absorption lines; without the compression along our line of sight, Mrk 231 would appear as an ordinary iron low-ionization, broad absorption line quasar.

  14. Anti-proliferative effect of biogenic gold nanoparticles against breast cancer cell lines (MDA-MB-231 & MCF-7)

    Energy Technology Data Exchange (ETDEWEB)

    Uma Suganya, K.S. [Centre for Ocean Research, Sathyabama University, Chennai 600119 (India); Govindaraju, K., E-mail: govindtu@gmail.com [Centre for Ocean Research, Sathyabama University, Chennai 600119 (India); Ganesh Kumar, V. [Centre for Ocean Research, Sathyabama University, Chennai 600119 (India); Prabhu, D.; Arulvasu, C. [Department of Zoology, University of Madras, Guindy campus, Chennai 600 025 (India); Stalin Dhas, T.; Karthick, V.; Changmai, Niranjan [Centre for Ocean Research, Sathyabama University, Chennai 600119 (India)

    2016-05-15

    Highlights: • Biosynthesis of stable and well dispersed predominantly spherical gold nanoparticles of size around ∼12.5 nm. • Anticancer assessment of gold nanoparticles on MDA-MB-231 and MCF-7 cell lines. • AuNPs were found non toxic to normal HMEC cells. • Flow cytometry results revealed significant arrest in cell proliferation in early G0/G1 to S phase. - Abstract: Breast cancer is a major complication in women and numerous approaches are being developed to overcome this problem. In conventional treatments such as chemotherapy and radiotherapy the post side effects cause an unsuitable effect in treatment of cancer. Hence, it is essential to develop a novel strategy for the treatment of this disease. In the present investigation, a possible route for green synthesis of gold nanoparticles (AuNPs) using leaf extract of Mimosa pudica and its anticancer efficacy in the treatment of breast cancer cell lines is studied. The synthesized nanoparticles were found to be effective in killing cancer cells (MDA-MB-231 & MCF-7) which were studied using various anticancer assays (MTT assay, cell morphology determination, cell cycle analysis, comet assay, Annexin V-FITC/PI staining and DAPI staining). Cell morphological analysis showed the changes occurred in cancer cells during the treatment with AuNPs. Cell cycle analysis revealed apoptosis in G{sub 0}/G{sub 1} to S phase. Similarly in Comet assay, there was an increase in tail length in treated cells in comparison with the control. Annexin V-FITC/PI staining assay showed prompt fluorescence in treated cells indicating the translocation of phosphatidylserine from the inner membrane. PI and DAPI staining showed the DNA damage in treated cells.

  15. 钢板固定治疗胫骨平台骨折231例临床疗效观察%Observation on Clinical Effect of Plate Fixation for Tibial Plateau Fracture in 231 Cases

    Institute of Scientific and Technical Information of China (English)

    王春鹏

    2015-01-01

    Objective To discuss the clinical effect of different plate ifxation methods for tibial plateau fracture. Methods 231 patients with tibial plateau fracture were given plate ifxation in our hospital from 2012 to 2014. The clinical effects were made a retrospective analysis. 112 cases with unilateral locking plate ifxation was A group, 119 cases with bilateral anatomic plate ifxation was B group. The healing time of patients with fracture ifxation and their function of knee joint were compared between the two groups. Results The healing time and knee function in group A were signiifcantly better than the control group, P<0.05, there were differences. Conclusion Unilateral locking plate fixation for tibial plateau fracture can shorten the fracture healing time, make knee joint rehabilitation early and the knee functions are better.%目的:探讨不同钢板固定方式治疗胫骨平台骨折的效果。方法回顾性分析2012~2014年在我院进行胫骨平台骨折内固定治疗的患者231例,其中112例采用单侧锁定钢板内固定为A组,119例采用双侧解剖钢板内固定为B组,对比两组不同内固定方式患者的骨折愈合时间,膝关节功能。结果 A组患者的骨折愈合时间,以及膝关节功能优于对照组,P<0.05,差异有统计学意义。结论单侧锁定钢板内固定治疗胫骨平台骨折,骨折能够较早的愈合,膝关节得到较早的康复锻炼,膝关节功能较好。

  16. The cerebro-oculo-facio-skeletal syndrome point mutation F231L in the ERCC1 DNA repair protein causes dissociation of the ERCC1-XPF complex

    NARCIS (Netherlands)

    M. Faridounnia (Maryam); H. Wienk (Hans); L. Kovačič (Lidija); G.E. Folkers (Gert); N.G.J. Jaspers (Nicolaas); R. Kaptein (Robert); J.H.J. Hoeijmakers (Jan); R. Boelens (Rolf)

    2015-01-01

    textabstractThe ERCC1-XPF heterodimer, a structure-specific DNA endonuclease, is best known for its function in the nucleotide excision repair (NER) pathway. The ERCC1 point mutation F231L, located at the hydrophobic interaction interface of ERCC1 (excision repair cross-complementation group 1) and

  17. Cytotoxicity enhancement in MDA-MB-231 cells by the combination treatment of tetrahydropalmatine and berberine derived from Corydalis yanhusuo W. T. Wang

    Directory of Open Access Journals (Sweden)

    Yan Zhao

    2014-04-01

    Conclusion: Our findings suggested that the combination of THP and Ber might be beneficial for anti-proliferation of MDA-MB-231 breast cancer cells through a significant synergy effect. [J Intercult Ethnopharmacol 2014; 3(2.000: 68-72

  18. Major triterpenoids in Chinese hawthorn "Crataegus pinnatifida" and their effects on cell proliferation and apoptosis induction in MDA-MB-231 cancer cells.

    Science.gov (United States)

    Wen, Lingrong; Guo, Ruixue; You, Lijun; Abbasi, Arshad Mehmood; Li, Tong; Fu, Xiong; Liu, Rui Hai

    2017-02-01

    The cytotoxicity and antiproliferative effect of phytochemicals presenting in the fruits of Chinese hawthorn (Crataegus pinnatifida) were evaluated. Shanlihong (Crataegus pinnatifida Bge. var. major N.E.Br.) variety possessed significant levels of flavonoids and triterpenoids, and showed potent antiproliferative effect against HepG2, MCF-7 and MDA-MB- 231 human cancer cells lines. Triterpenoids-enriched fraction (S9) prepared by Semi-preparative HPLC, and its predominant ingredient ursolic acid (UA) demonstrated remarkably antiproliferative activities for all the tested cancer cell lines. DNA flow cytometric analysis showed that S9 fraction and UA significantly induced G1 arrest in MDA-MB-231 cells in a dose-dependent manner. Western blotting analysis revealed that S9 fraction and UA significantly induced PCNA, CDK4, and Cyclin D1 downregulation in MDA-MB-231 cells, followed by p21(Waf1/Cip1) up-regulation. Additionally, flow cytometer and DNA ladder assays indicated that S9 fraction and UA significantly induced MDA-MB-231 cells apoptosis. Mitochondrial death pathway was involved in this apoptosis as significantly induced caspase-9 and caspase-3 activation. These results suggested that triterpenoids-enriched fraction and UA exhibited antiproliferative activity through the cell cycle arrest and apoptosis induction, and was majorly responsible for the potent anticancer activity of Chinese hawthorn. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. 40 CFR 264.231 - Special requirements for hazardous wastes FO20, FO21, FO22, FO23, FO26, and FO27.

    Science.gov (United States)

    2010-07-01

    ... HAZARDOUS WASTE TREATMENT, STORAGE, AND DISPOSAL FACILITIES Surface Impoundments § 264.231 Special requirements for hazardous wastes FO20, FO21, FO22, FO23, FO26, and FO27. (a) Hazardous Wastes FO20, FO21, FO22... surface impoundments managing hazardous wastes FO20, FO21, FO22, FO23, FO26, and FO27 in order to reduce...

  20. 49 CFR 231.28 - Box and other house cars with roof hatches built or placed in service after October 1, 1966.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Box and other house cars with roof hatches built... RAILROAD SAFETY APPLIANCE STANDARDS § 231.28 Box and other house cars with roof hatches built or placed in... other house cars with roof hatches. Box and other house cars with roof hatches built on or before...

  1. 49 CFR 231.27 - Box and other house cars without roof hatches or placed in service after October 1, 1966.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Box and other house cars without roof hatches or... SAFETY APPLIANCE STANDARDS § 231.27 Box and other house cars without roof hatches or placed in service...) Number. (i) Each box or other house car without roof hatches shall be equipped with an efficient...

  2. Transcriptional effects of Organochlorine o,p′-DDT and its Metabolite p,p′-DDE in Transfected MDA-MB 231 and MCF-7 Breast Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Ehsan zayerzadeh

    2015-04-01

    Conclusion: In conclusion, our results revealed that o,p’-DDT has not estrogenic activity in a classical mechanism in transfected MDA-MB 231 breast cancer cells while has estrogenic activity in a classical mechanism in transfected MCF-7 human breast cancer cell line.

  3. {\\it NuSTAR} Reveals an Intrinsically X-ray Weak Broad Absorption Line Quasar in the Ultraluminous Infrared Galaxy Markarian 231

    CERN Document Server

    Teng, Stacy H; Harrison, F A; Luo, B; Alexander, D M; Bauer, F E; Boggs, S E; Christensen, F E; Comastri, A; Craig, W W; Fabian, A C; Farrah, D; Fiore, F; Gandhi, P; Grefenstette, B W; Hailey, C J; Hickox, R C; Madsen, K K; Ptak, A F; Rigby, J R; Risaliti, G; Saez, C; Stern, D; Veilleux, S; Walton, D J; Wik, D R; Zhang, W W

    2014-01-01

    We present high-energy (3--30 keV) {\\it NuSTAR} observations of the nearest quasar, the ultraluminous infrared galaxy (ULIRG) Markarian 231 (Mrk 231), supplemented with new and simultaneous low-energy (0.5--8 keV) data from {\\it Chandra}. The source was detected, though at much fainter levels than previously reported, likely due to contamination in the large apertures of previous non-focusing hard X-ray telescopes. The full band (0.5--30 keV) X-ray spectrum suggests the active galactic nucleus (AGN) in Mrk 231 is absorbed by a patchy and Compton-thin (N$_{\\rm H} \\sim1.2^{+0.3}_{-0.3}\\times10^{23}$ cm$^{-2}$) column. The intrinsic X-ray luminosity (L$_{\\rm 0.5-30 keV}\\sim1.0\\times10^{43}$ erg s$^{1}$) is extremely weak relative to the bolometric luminosity where the 2--10 keV to bolometric luminosity ratio is $\\sim$0.03% compared to the typical values of 2--15%. Additionally, Mrk 231 has a low X-ray-to-optical power law slope ($\\alpha_{\\rm OX}\\sim-1.7$). It is a local example of a low-ionization broad absorpti...

  4. Effect of 3-bromopyruvate acid on the redox equilibrium in non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cells.

    Science.gov (United States)

    Kwiatkowska, Ewa; Wojtala, Martyna; Gajewska, Agnieszka; Soszyński, Mirosław; Bartosz, Grzegorz; Sadowska-Bartosz, Izabela

    2016-02-01

    Novel approaches to cancer chemotherapy employ metabolic differences between normal and tumor cells, including the high dependence of cancer cells on glycolysis ("Warburg effect"). 3-Bromopyruvate (3-BP), inhibitor of glycolysis, belongs to anticancer drugs basing on this principle. 3-BP was tested for its capacity to kill human non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cells. We found that 3-BP was more toxic for MDA-MB-231 cells than for MCF-7 cells. In both cell lines, a statistically significant decrease of ATP and glutathione was observed in a time- and 3-BP concentration-dependent manner. Transient increases in the level of reactive oxygen species and reactive oxygen species was observed, more pronounced in MCF-7 cells, followed by a decreasing tendency. Activities of glutathione peroxidase, glutathione reductase (GR) and glutathione S-transferase (GST) decreased in 3-BP treated MDA-MB-231 cells. For MCF-7 cells decreases of GR and GST activities were noted only at the highest concentration of 3-BP.These results point to induction of oxidative stress by 3-BP via depletion of antioxidants and inactivation of antioxidant enzymes, more pronounced in MDA-MB-231 cells, more sensitive to 3-BP.

  5. Neohesperidin induces cellular apoptosis in human breast adenocarcinoma MDA-MB-231 cells via activating the Bcl-2/Bax-mediated signaling pathway.

    Science.gov (United States)

    Xu, Fei; Zang, Jia; Chen, Daozhen; Zhang, Ting; Zhan, Huiying; Lu, Mudan; Zhuge, Hongxiang

    2012-11-01

    Neohesperidin, a flavonoid compound found in high amounts in Poncirus trifoliata, has free radical scavenging activity. For the first time, our study indicated that neohesperidin also induces cell apoptosis in human breast adenocarcinoma MDA-MB-231 cells, which was possibly mediated by regulating the P53/Bcl-2/Bax pathway. MDA-MB-231 cells were subjected to treatment with neohesperidin. MTT and Trypan blue exclusion assays were applied to assess the cell viability. The morphological changes of cells were observed using an inverted microscope, and cell apoptosis was detected by flow cytometric analysis. Immunoblot analysis was conducted to evaluate the protein expressions of apoptosis-related genes, including P53, Bcl-2 and Bax. Our results indicated that the proliferation of MDA-MB-231 cells was inhibited by the treatment with neohesperidin in a time- and dose-dependent manner. The IC50 values of neohesperidin at 24 and 48 h were 47.4 +/- 2.6 microM and 32.5 +/- 1.8 microM, respectively. The expressions of P53 and Bax in the neohesperidin-treated cells were significantly up-regulated, while that of Bcl-2 was down-regulated. Our study suggested that neohesperidin could induce apoptosis of MDA-MB-231 cells, a process which was associated with the activation of the Bcl-2/Bax-mediated signaling pathway.

  6. Platycodin D from Platycodonis Radix enhances the anti-proliferative effects of doxorubicin on breast cancer MCF-7 and MDA-MB-231 cells.

    Science.gov (United States)

    Tang, Zheng-Hai; Li, Ting; Gao, Hong-Wei; Sun, Wen; Chen, Xiu-Ping; Wang, Yi-Tao; Lu, Jin-Jian

    2014-01-01

    It has been demonstrated that platycodin D (PD) exhibits anti-cancer activities. This study aims to investigate the anti-proliferative effects of the combination of PD and doxorubicin (DOX) on human breast cancer cells (MCF-7 and MDA-MB-231 cells). The anti-proliferative effects of different dosages of PD, DOX, and PD + DOX on MCF-7 and MDA-MB-231 cells were determined by the MTT assay. The 10 μM PD, 5 μM DOX, and 10 μM PD + 5 μM DOX induced-protein expression of apoptosis-related molecules on MCF-7 and MDA-MB-231 cells were detected by western blot. The 10 μM PD, 5 μM DOX and 10 μM PD + 5 μM DOX-induced mitochondrial membrane potential changes on MCF-7 and MDA-MB-231 cells were stained with JC-1 before visual determination. The intracellular accumulations of DOX, induced by 10 μM PD, 5 μM DOX and 10 μM PD + 5 μM DOX, were detected by flow cytometry. PD enhanced anti-cancer activities of DOX were observed in both MCF-7 and MDA-MB-231 cell lines. Compared with mono treatment, the combined treatment increased the protein expression of cleaved poly (ADP-ribose) polymerase and decreased the mitochondrial membrane potential. The combined treatment with PD did not obviously increase the accumulation of DOX in MCF-7 cells (1.66 ± 0.13 in DOX-treated group, and 1.69 ± 0.06 in PD + DOX-treated group, P = 0.76), but it significantly increased the accumulation of DOX in MDA-MB-231 cells (1.76 ± 0.17 in DOX-treated group, 2.09 ± 0.02 in PD + DOX-treated group, P = 0.027). The combined treatment of DOX and PD exhibited stronger anti-proliferative effects on MCF-7 and MDA-MB-231 cells than DOX and PD treatment did.

  7. [27-O-(E)-p-coumaric acyl ursolic acid via JNK/SAPK signal pathway regulates apoptosis of human breast cancer MDA-MB-231 cell line].

    Science.gov (United States)

    Wang, Hong-ting; Wang, Cun-qin

    2015-02-01

    27-O-(E)-p-coumaric acyl ursolic acid( DY-17) from Ilex latifolia is a compound of the monomer. To investigate the DY-17 inducing apoptosis in the human breast cancer cell line, the MDA-MB-231 cells were used as research object in this experiment. The proliferation activity of the MDA-MB-231 cells stimulated with the different concentrations of DY-17 (20, 40 µmol · L(-1)) was detected at different time( 12, 24, 36, 48, 60,72 h) . We surveyed the DY-17 inducing apoptosis of the MDA-MB-231 cells with the fluorescent staining technology. The rate of MDA-MB-231 cells apoptosis and necrosis was determined by flow cell cytometry (FCC). Moreover, expression of JNK, phosphorylated JNK, Bax, PARP shear and caspase-3 shear related to JNK/SAPK pathways were investigated in every group ( control group, EGF group, EGF + DY-17 40 µmol · L(1) group and EGF + SP600125 group) with Western blot. The MTT results showed that, in the presence of DY-17, the proliferation activity of MDA-MB-231 cells decreased in a dose-dependent and time-dependent manner. The apoptosis and necrosis rates of MDA-MB-231 cells with DY-17(20, 40 µmol · L(-1)) groups was respectively 31.86%, 49.91% by flow cytometry and significantly increased compared with control group under Fluores- cence microscopy. Up-regulation of the JNK phosphorylation protein expression was observed in EGF group compared with control group. In addition, markedly decreased the expression of JNK phosphorylation protein were also surveyed in EGF + DY-17 40 µmol · L(-1) group compared with EGF group. The expression of Bax, shear PARP and shear caspase-3 protein in EGF + DY-17 40 µmol · L(-1) group were significantly increased in comparison with EGF group. The results showed DY-17 induced apoptosis of human breast cancer MDA-MB-231 cell line related to down-regulating JNK/SAPK signal pathways.

  8. 230Th and 231Pa on GEOTRACES GA03, the U.S. GEOTRACES North Atlantic transect, and implications for modern and paleoceanographic chemical fluxes

    Science.gov (United States)

    Hayes, Christopher T.; Anderson, Robert F.; Fleisher, Martin Q.; Huang, Kuo-Fang; Robinson, Laura F.; Lu, Yanbin; Cheng, Hai; Edwards, R. Lawrence; Moran, S. Bradley

    2015-06-01

    The long-lived uranium decay products 230Th and 231Pa are widely used as quantitative tracers of adsorption to sinking particles (scavenging) in the ocean by exploiting the principles of radioactive disequilibria. Because of their preservation in the Pleistocene sediment record and through largely untested assumptions about their chemical behavior in the water column, the two radionuclides have also been used as proxies for a variety of chemical fluxes in the past ocean. This includes the vertical flux of particulate matter to the seafloor, the lateral flux of insoluble elements to continental margins (boundary scavenging), and the southward flux of water out of the deep North Atlantic. In a section of unprecedented vertical and zonal resolution, the distributions of 230Th and 231Pa across the North Atlantic shed light on the marine cycling of these radionuclides and further inform their use as tracers of chemical flux. Enhanced scavenging intensities are observed in benthic layers of resuspended sediments on the eastern and western margins and in a hydrothermal plume emanating from the Mid-Atlantic Ridge. Boundary scavenging is clearly expressed in the water column along a transect between Mauritania and Cape Verde which is used to quantify a bias in sediment fluxes calculated using 230Th-normalization and to demonstrate enhanced 231Pa removal from the deep North Atlantic by this mechanism. The influence of deep ocean ventilation that leads to the southward export of 231Pa is apparent. The 231Pa/230Th ratio, however, predominantly reflects spatial variability in scavenging intensity, complicating its applicability as a proxy for the Atlantic meridional overturning circulation.

  9. Polysaccharide from Sepia esculenta ink and cisplatin inhibit synergistically proliferation and metastasis of triple-negative breast cancer MDA-MB-231 cells

    Directory of Open Access Journals (Sweden)

    Hua-Zhong Liu

    2016-12-01

    Full Text Available Objective(s: This paper aims to investigate synergistic inhibition of polysaccharide from Sepia esculenta ink (SIP, a newly isolated marine polysaccharide in our laboratory, on breast cancer MDA-MB-231 cells exposed to cisplatin. Materials and Methods: Cell viability of MDA-MB-231 cells was determined by CCK 8 assay. Median-effect concentration was analyzed using Chou-Talalay method that was also subjected to determine cell inhibition ratio and combined index, as well as interaction between SIP and cisplatin. Proliferation and migration abilities were detected with plate colony formation assay and cell wound scratch assay, respectively. Expression of MMP-2 and MMP-9 proteins was measured with Western blot assay. Results: Data showed that SIP not only suppressed proliferation and migration of MDA-MB-231 cells, and expression of MMP-2 and MMP-9 proteins, also promoted inhibition of cisplatin on proliferation, migration and MMPs expression of MDA-MB-231 cells, which indicates synergy inhibition of drug combination of SIP and cisplatin on breast cancer cells. The median-effect concentrations of cisplatin and SIP were 4.9 and 1659.6 μg/ml, respectively. Whereas the concentration of combination drug was 158.5 μg/ml. The data indicated that drug combination can decrease dosages of the two single agents, especially the usual dosage of cisplatin. Conclusion: This research demonstrated that SIP repressed proliferation and metastasis of MDA-MB-231 cells and promoted anticancer effect of cisplatin on the breast cancer cells. The data suggested that SIP is a potential natural drug that can be used as an auxiliary medicine alongside chemotherapy in treating breast cancer.

  10. Comparing Apoptosis and Necrosis Effects of Arctium Lappa Root Extract and Doxorubicin on MCF7 and MDA-MB-231 Cell Lines

    Science.gov (United States)

    Ghafari, Fereshteh; Rajabi, Mohammad Reza; Mazoochi, Tahereh; Taghizadeh, Mohsen; Nikzad, Hossein; Atlasi, Mohammad Ali; Taherian, Aliakbar

    2017-03-01

    Objective: Breast cancer is a heterogeneous disease and very common malignancy in women worldwide. The efficacy of chemotherapy as an important part of breast cancer treatment is limited due to its side effects. While pharmaceutical companies are looking for better chemicals, research on traditional medicines that generally have fewer side effects is quite interesting. In this study, apoptosis and necrosis effect of Arctium lappa and doxorubicin was compared in MCF7, and MDA-MB-231 cell lines. Materials and Methods: MCF7 and MDA-MB-231 cells were cultured in RPMI 1640 containing 10% FBS and 100 U/ml penicillin/streptomycin. MTT assay and an annexin V/propidium iodide (AV/PI) kit were used respectively to compare the survival rate and apoptotic effects of different concentrations of doxorubicin and Arctium lappa root extract on MDA-MB-231 and MCF7 cells. Results: Arctium lappa root extract was able to reduce cell viability of the two cell lines in a dose and time dependent manner similar to doxorubicin. Flow cytometry results showed that similar to doxorubicin, Arctium Lappa root extract had a dose and time dependent apoptosis effect on both cell lines. 10μg/mL of Arctium lappa root extract and 5 μM of doxorubicin showed the highest anti-proliferative and apoptosis effect in MCF7 and MDA231 cells. Conclusion: The MCF7 (ER/PR-) and MDA-MB-231 (ER/PR+) cell lines represent two major breast cancer subtypes. The similar anti-proliferative and apoptotic effects of Arctium lappa root extract and doxorubicin (which is a conventional chemotherapy drug) on two different breast cancer cell lines strongly suggests its anticancer effects and further studies. Creative Commons Attribution License

  11. A novel intracellular isoform of VEGFR-1 activates Src and promotes cell invasion in MDA-MB-231 breast cancer cells.

    Science.gov (United States)

    Mezquita, Belén; Mezquita, Jovita; Pau, Montserrat; Mezquita, Cristóbal

    2010-06-01

    Two types of VEGFR-1 receptors have been characterized: a full-length transmembrane receptor and a truncated extracellular soluble isoform (sVEGFR-1). We report here the characterization, in normal and cancer cells, of a new family of intracellular isoforms of VEGFR-1 resulting from alternative initiation of transcription in intronic sequences of the gene. While the classical isoforms of VEGFR-1 were barely detectable in MDA-MB-231 breast cancer cells, one of the intracellular isoforms transcribed from intron 21 (i(21)VEGFR-1) was the main isoform expressed in these cells. The new transcript encodes for a protein that contains only the phosphotransferase domain and the carboxyterminal tail of VEGFR-1. Treatment of MDA-MB-231 cells with siRNA specific for the tyrosine domain of VEGFR-1 suppressed the expression of i(21)VEGFR-1, downregulated phosphorylation of Src at tyrosine 418, and reduced markedly the invasion capacity of these cells in vitro. Accordingly, overexpression of transfected i(21)VEGFR-1 in MDA-MB-231 cells upregulated the active form of Src and increased invasiveness of MDA-MB-231 cells. The expression of i(21)VEGFR-1 in MDA-MB-231 cells was inhibited by retinoic acid. Both, activation of Src and downregulation by retinoic acid, have been reported in other intracellular members of the Fms/Kit/PDGFR family of tyrosine kinases, particularly in the intracellular isoform of c-kit, analogous structurally to i(21)VEGFR-1 and frequently expressed in cancer cells. (c) 2010 Wiley-Liss, Inc.

  12. Induction of G1-phase cell cycle arrest and apoptosis pathway in MDA-MB-231 human breast cancer cells by sulfated polysaccharide extracted from Laurencia papillosa.

    Science.gov (United States)

    Murad, Hossam; Hawat, Mohammad; Ekhtiar, Adnan; AlJapawe, Abdulmunim; Abbas, Assef; Darwish, Hussein; Sbenati, Oula; Ghannam, Ahmed

    2016-01-01

    Marine algae consumption is linked to law cancer incidences in countries that traditionally consume marine products. Hence, Phytochemicals are considered as potential chemo-preventive and chemotherapeutic agents against cancer. We investigated the effects of the algal sulfated polysaccharide extract (ASPE) from the red marine alga L. papillosa on MDA-MB-231 human breast cancer cell line. Flow cytometry analysis was performed to study the cell viability, cell cycle arrest and apoptosis. Changes in the expression of certain genes associated with cell cycle regulation was conducted by PCR real time analyses. Further investigations on apoptotic molecules was performed by ROS measurement and protein profiling. ASPE at low doses (10 µg/ml), inhibited cell proliferation, and arrested proliferating MDA-MB-231 cells at G1-phase. However, higher doses (50 µg/ml), triggered apoptosis in those cells. The low dose of ASPE also caused up-regulation of Cip1/p21 and Kip1/p27 and down-regulation of cyclins D1, D2, and E1 transcripts and their related cyclin dependent kinases: Cdk2, Cdk4, and Cdk6. The higher doses of ASPE initiated a dose-dependent apoptotic death in MDA-MB-231 by induction of Bax transcripts, inhibition of Bcl-2 and cleavage of Caspase-3 protein. Over-generation of reactive oxygen species (ROS) were also observed in MDA-MB-231 treated cells. These findings indicated that ASPE induces G1-phase arrest and apoptosis in MDA-MB-231 cells. ASPE may serve as a potential therapeutic agent for breast cancer.

  13. Polysaccharide from Sepia esculenta ink and cisplatin inhibit synergistically proliferation and metastasis of triple-negative breast cancer MDA-MB-231 cells.

    Science.gov (United States)

    Liu, Hua-Zhong; Xiao, Wei; Gu, Yi-Peng; Tao, Ye-Xing; Zhang, Da-Yan; Du, Hui; Shang, Jiang-Hua

    2016-12-01

    This paper aims to investigate synergistic inhibition of polysaccharide from Sepia esculenta ink (SIP), a newly isolated marine polysaccharide in our laboratory, on breast cancer MDA-MB-231 cells exposed to cisplatin. Cell viability of MDA-MB-231 cells was determined by CCK 8 assay. Median-effect concentration was analyzed using Chou-Talalay method that was also subjected to determine cell inhibition ratio and combined index, as well as interaction between SIP and cisplatin. Proliferation and migration abilities were detected with plate colony formation assay and cell wound scratch assay, respectively. Expression of MMP-2 and MMP-9 proteins was measured with Western blot assay. Data showed that SIP not only suppressed proliferation and migration of MDA-MB-231 cells, and expression of MMP-2 and MMP-9 proteins, also promoted inhibition of cisplatin on proliferation, migration and MMPs expression of MDA-MB-231 cells, which indicates synergy inhibition of drug combination of SIP and cisplatin on breast cancer cells. The median-effect concentrations of cisplatin and SIP were 4.9 and 1659.6 μg/ml, respectively. Whereas the concentration of combination drug was 158.5 μg/ml. The data indicated that drug combination can decrease dosages of the two single agents, especially the usual dosage of cisplatin. This research demonstrated that SIP repressed proliferation and metastasis of MDA-MB-231 cells and promoted anticancer effect of cisplatin on the breast cancer cells. The data suggested that SIP is a potential natural drug that can be used as an auxiliary medicine alongside chemotherapy in treating breast cancer.

  14. A potential peptide vector that allows targeted delivery of a desired fusion protein into the human breast cancer cell line MDA-MB-231.

    Science.gov (United States)

    Liu, Wei Qing; Yang, Jun; Hong, Min; Gao, Chang E; Dong, Jian

    2016-06-01

    Effective control of breast cancer has been primarily hampered by a lack of tumor specificity in treatments. One potential way to improve targeting specificity is to develop novel vectors that specifically bind to and are internalized by tumor cells. Through a phage display library, an 11-L-amino acid peptide, PI (sequence, CASPSGALRSC), was selected. PI was labeled with fluorescein isothiocyanate (FITC) and named PI-FITC. Subsequently, the specific affinity of PI-FITC to MDA-MB-231 human breast cancer cells and other cancer cell lines was observed by confocal microscopy. Our previous study established that PI-FITC also shows affinity to Calu-1 human lung carcinoma cells and major histocompatibility complex class I antigen molecules; therefore, the cytomembrane proteins of the cell lines were analyzed to determine those that were common to the two cell lines and may be associated with transmembrane transduction. To further test the delivery ability of PI to MDA-MB-231 cells, PI-glutathione-S-transferase (GST) was constructed and the internalization of this fusion protein was visualized by immunofluorescence microscopy. The results revealed that PI exhibited specific affinity to MDA-MB-231 cells. Use of membrane transport inhibitors indicated that macropinocytosis and caveolin-mediated endocytosis may be involved in the endocytosis of PI. In addition, 11 membrane proteins common to MDA-MB-231 and Calu-1 may be associated with transmembrane transduction. In summary, PI was able to deliver PI-GST into MDA-MB-231 cells. Thus, PI could be modified to be a potential vector, and may contribute to the development of targeted therapeutic strategies for breast cancer.

  15. Antioxidant Activity and ROS-Dependent Apoptotic Effect of Scurrula ferruginea (Jack) Danser Methanol Extract in Human Breast Cancer Cell MDA-MB-231

    Science.gov (United States)

    Marvibaigi, Mohsen; Amini, Neda; Supriyanto, Eko; Abdul Majid, Fadzilah Adibah; Kumar Jaganathan, Saravana; Jamil, Shajarahtunnur; Hamzehalipour Almaki, Javad; Nasiri, Rozita

    2016-01-01

    Scurrula ferruginea (Jack) Danser is one of the mistletoe species belonging to Loranthaceae family, which grows on the branches of many deciduous trees in tropical countries. This study evaluated the antioxidant activities of S. ferruginea extracts. The cytotoxic activity of the selected extracts, which showed potent antioxidant activities, and high phenolic and flavonoid contents, were investigated in human breast cancer cell line (MDA-MB-231) and non-cancer human skin fibroblast cells (HSF-1184). The activities and characteristics varied depending on the different parts of S. ferruginea, solvent polarity, and concentrations of extracts. The stem methanol extract showed the highest amount of both phenolic (273.51 ± 4.84 mg gallic acid/g extract) and flavonoid contents (163.41 ± 4.62 mg catechin/g extract) and strong DPPH• radical scavenging (IC50 = 27.81 μg/mL) and metal chelation activity (IC50 = 80.20 μg/mL). The stem aqueous extract showed the highest ABTS•+ scavenging ability. The stem methanol and aqueous extracts exhibited dose-dependent cytotoxic activity against MDA-MB-231 cells with IC50 of 19.27 and 50.35 μg/mL, respectively. Furthermore, the extracts inhibited the migration and colony formation of MDA-MB-231 cells in a concentration-dependent manner. Morphological observations revealed hallmark properties of apoptosis in treated cells. The methanol extract induced an increase in ROS generation and mitochondrial depolarization in MDA-MB-231 cells, suggesting its potent apoptotic activity. The present study demonstrated that the S. ferruginea methanol extract mediated MDA-MB-231 cell growth inhibition via induction of apoptosis which was confirmed by Western blot analysis. It may be a potential anticancer agent; however, its in vivo anticancer activity needs to be investigated. PMID:27410459

  16. Stable transfection of estrogen receptor-alpha suppresses expression of interleukin-8 in MDA-MB-231 breast cancer cells%转染ERα基因对MDA-MB-231乳腺癌细胞白细胞介素-8表达的影响

    Institute of Scientific and Technical Information of China (English)

    张辉; 林颖; 肖颖; 王三明; 刘祥厦; 王深明

    2010-01-01

    目的 通过转染GFP-C1-ERα质粒建立稳定表达ERα的MDA-MB-23l细胞株,观察ERα对该细胞株白细胞介素(IL)-8表达的影响.方法 pEGFP-C1-ERα质粒经酶切和测序后转染MDA-MB-231细胞,使用G418筛选出稳定表达的克隆并鉴定.使用荧光逆转录-聚合酶链反应(RT-PCR)分别测定稳定转染ERα的MDA-MB-231细胞、MDA-MB-231细胞及MCF-7细胞的IL-8mRNA的表达,使用酶联免疫吸附试验(ELISA)法测定细胞上清液IL-8的浓度.结果 成功建立ERα阳性表达的MDA-MB-231细胞株,转染ERα的细胞株IL-8 mRNA的合成(105±16)ng/L明显低于MDA-MB-231细胞(195±32)ng/L(P<0.05),但仍然高于MCF-7细胞(32±4)ng/L(P<0.05),转染后细胞上清液IL-8浓度较未转染细胞明显降低,分别为(3499±312)ng/L和(6788±427)ng/L(P<0.05),但仍然高于MCF-7细胞(1846±44)ng/L(P<0.05).结论 稳定转染ERα基因抑制了MDA-MB-231细胞的IL-8的合成和分泌.%Objective To construct stable MDA-MB-231 breast cancer cell line expressing estrogen receptor-α (ER-α) ,and explore the effect of ERα on interleukin (IL) -8 expression. Methods The GFP-C1-ERα plasmids were stably transfected into ER-negative MDA-MB-231 cells. Forty-eight hours posttransfection, the media was replaced with C418-containing media. Individual colonies were picked following 2 weeks of selection. The expression of IL-8 mRNA and the IL-8 secretion concentration were assayed in MDA-MB-231 ,ER-α transfected MDA-MB-231 and MCF-7 cell lines. Results The ERα stable transfectants in MDA-MB-231 cells were constructed successfully according Western blotting of ERα protein. The level of IL-8 mRNA and IL-8 secretion in ERα tranfected MDA-MB-231 cells were lower than which in MDA-MB-231 cells [(105 ±16) vs (195 ±32) ng/L,and (3499 ±312) vs (6788 ±427) ng/L,P <0. 05]but were still higher than which in MCF-7 cells [(32 ± 4) ng/L and (1846 ± 44) ng/L, P <0. 05]. Conclusion ERα stable transfection inhibits the expression and

  17. Effect of 3-Bromopyruvic acid combined with docetaxel on the proliferation and apoptosis of human breast neoplasm MDA-MB-231 cells%3-溴丙酮酸联合多西他赛对人乳腺癌MDA-MB-231细胞增殖和凋亡的影响

    Institute of Scientific and Technical Information of China (English)

    刘玲玲; 孙一鸣; 赵素容; 刘浩

    2016-01-01

    目的:观察3-溴丙酮酸(3-Bromopyruvic acid,3-BrPA)联合多西他赛(docetaxel,DTX)对乳腺癌MDA-MB-231细胞增殖和凋亡的影响,并探讨相关分子机制.方法:MTT实验检测不同药物处理后乳腺癌MDA-MB-231细胞株存活情况;流式细胞术PI单染法检测用药后细胞凋亡情况;ATP试剂盒检测3-BrPA对细胞内ATP水平的影响;线粒体膜电位检测试剂盒(JC-1)检测3-BrPA对细胞线粒体膜电位的影响;Western blot检测用药后HexokinaseⅡ、Bax、Bcl-2和Mcl-1蛋白的表达情况.结果:3-BrPA、DTX均可抑制MDA-MB-231细胞的生长,呈现浓度依赖性,低浓度3-BrPA明显增强DTX对MDA-MB-231细胞的抑制作用;3-BrPA作用于MDA-MB-231细胞5h后,随药物浓度递增细胞内ATP水平递减;3-BrPA作用于MDA-MB-231细胞24h后,HKⅡ表达减少,且使细胞线粒体膜电位发生降低;40 μmol/L 3-BrPA联合2 μmol/L DTX处理24h后,MDA-MB-231细胞凋亡率为63.5%,较单独用药组的凋亡率明显提高(P<0.01).3-BrPA与DTX联合作用于MDA-MB-231细胞后,凋亡相关蛋白Bcl-2和Mcl-1的表达减弱,Bax的表达增强.结论:3-BrPA可增强DTX对乳腺癌MDA-MB-231细胞的增殖抑制作用以及凋亡诱导作用,其机制可能与下调Mcl-1和Bcl-2表达、上调Bax表达有关.

  18. Hypoxia counteracts taxol-induced apoptosis in MDA-MB-231 breast cancer cells: role of autophagy and JNK activation.

    Science.gov (United States)

    Notte, A; Ninane, N; Arnould, T; Michiels, C

    2013-05-16

    Cancer cell resistance against chemotherapy is still a heavy burden to improve anticancer treatments. Autophagy activation and the development of hypoxic regions within the tumors are known to promote cancer cell resistance. Therefore, we sought to evaluate the role of autophagy and hypoxia on the taxol-induced apoptosis in MDA-MB-231 breast cancer cells. The results showed that taxol induced apoptosis after 16 h of incubation, and that hypoxia protected MDA-MB-231 cells from taxol-induced apoptosis. In parallel, taxol induced autophagy activation already after 2 h of incubation both under normoxia and hypoxia. Autophagy activation after taxol exposure was shown to be a protective mechanism against taxol-induced cell death both under normoxia and hypoxia. However, at longer incubation time, the autophagic process reached a saturation point under normoxia leading to cell death, whereas under hypoxia, autophagy flow still correctly took place allowing the cells to survive. Autophagy induction is induced after taxol exposure via mechanistic target of rapamycin (mTOR) inhibition, which is more important in cells exposed to hypoxia. Taxol also induced c-Jun N-terminal kinase (JNK) activation and phosphorylation of its substrates B-cell CLL/lymphoma 2 (Bcl2) and BCL2-like 1 (BclXL) under normoxia and hypoxia very early after taxol exposure. Bcl2 and BclXL phosphorylation was decreased more importantly under hypoxia after long incubation time. The role of JNK in autophagy and apoptosis induction was studied using siRNAs. The results showed that JNK activation promotes resistance against taxol-induced apoptosis under normoxia and hypoxia without being involved in induction of autophagy. In conclusion, the resistance against taxol-induced cell death observed under hypoxia can be explained by a more effective autophagic flow activated via the classical mTOR pathway and by a mechanism involving JNK, which could be dependent on Bcl2 and BclXL phosphorylation but independent of

  19. Hypoxia counteracts taxol-induced apoptosis in MDA-MB-231 breast cancer cells: role of autophagy and JNK activation

    Science.gov (United States)

    Notte, A; Ninane, N; Arnould, T; Michiels, C

    2013-01-01

    Cancer cell resistance against chemotherapy is still a heavy burden to improve anticancer treatments. Autophagy activation and the development of hypoxic regions within the tumors are known to promote cancer cell resistance. Therefore, we sought to evaluate the role of autophagy and hypoxia on the taxol-induced apoptosis in MDA-MB-231 breast cancer cells. The results showed that taxol induced apoptosis after 16 h of incubation, and that hypoxia protected MDA-MB-231 cells from taxol-induced apoptosis. In parallel, taxol induced autophagy activation already after 2 h of incubation both under normoxia and hypoxia. Autophagy activation after taxol exposure was shown to be a protective mechanism against taxol-induced cell death both under normoxia and hypoxia. However, at longer incubation time, the autophagic process reached a saturation point under normoxia leading to cell death, whereas under hypoxia, autophagy flow still correctly took place allowing the cells to survive. Autophagy induction is induced after taxol exposure via mechanistic target of rapamycin (mTOR) inhibition, which is more important in cells exposed to hypoxia. Taxol also induced c-Jun N-terminal kinase (JNK) activation and phosphorylation of its substrates B-cell CLL/lymphoma 2 (Bcl2) and BCL2-like 1 (BclXL) under normoxia and hypoxia very early after taxol exposure. Bcl2 and BclXL phosphorylation was decreased more importantly under hypoxia after long incubation time. The role of JNK in autophagy and apoptosis induction was studied using siRNAs. The results showed that JNK activation promotes resistance against taxol-induced apoptosis under normoxia and hypoxia without being involved in induction of autophagy. In conclusion, the resistance against taxol-induced cell death observed under hypoxia can be explained by a more effective autophagic flow activated via the classical mTOR pathway and by a mechanism involving JNK, which could be dependent on Bcl2 and BclXL phosphorylation but

  20. Metabolomic Dynamic Analysis of Hypoxia in MDA-MB-231 and the Comparison with Inferred Metabolites from Transcriptomics Data

    Directory of Open Access Journals (Sweden)

    Yufeng Jane Tseng

    2013-05-01

    Full Text Available Hypoxia affects the tumor microenvironment and is considered important to metastasis progression and therapy resistance. Thus far, the majority of global analyses of tumor hypoxia responses have been limited to just a single omics level. Combining multiple omics data can broaden our understanding of tumor hypoxia. Here, we investigate the temporal change of the metabolite composition with gene expression data from literature to provide a more comprehensive insight into the system level in response to hypoxia. Nuclear magnetic resonance spectroscopy was used to perform metabolomic profiling on the MDA-MB-231 breast cancer cell line under hypoxic conditions. Multivariate statistical analysis revealed that the metabolic difference between hypoxia and normoxia was similar over 24 h, but became distinct over 48 h. Time dependent microarray data from the same cell line in the literature displayed different gene expressions under hypoxic and normoxic conditions mostly at 12 h or earlier. The direct metabolomic profiles show a large overlap with theoretical metabolic profiles deduced from previous transcriptomic studies. Consistent pathways are glycolysis/gluconeogenesis, pyruvate, purine and arginine and proline metabolism. Ten metabolic pathways revealed by metabolomics were not covered by the downstream of the known transcriptomic profiles, suggesting new metabolic phenotypes. These results confirm previous transcriptomics understanding and expand the knowledge from existing models on correlation and co-regulation between transcriptomic and metabolomics profiles, which demonstrates the power of integrated omics analysis.

  1. Detection of HCN, HCO+ and HNC in the Mrk231 molecular outflow - Dense molecular gas in the AGN wind

    CERN Document Server

    Aalto, S; Muller, S; Winters, J M; van der Werf, P; Henkel, C; Costagliola, F; Neri, R

    2011-01-01

    We detect luminous emission from HCN, HCO+ and HNC 1--0 in the QSO ULIRG Mrk~231 with the IRAM Plateau de Bure Interferometer at 1."55 by 1."28 resolution. All three lines show broad line wings - which are particularly prominent for HCN. Velocities are found to be similar (750 km/s) to those found for CO 1-0. This is the first time bright HCN, HCO+ and HNC emission has been detected in a large-scale galactic outflow. We find that both the blue- and red-shifted line wings are spatially extended by at least 0."75 (700 pc) in a north-south direction. The line wings are brighter (relative to the line center intensity) in HCN than in CO 1-0 and line ratios suggest that the molecular outflow consists of dense (n>10E4 cmE-3) and clumpy gas with a high HCN abundance X(HCN)>10E-8. These properties are consistent with the molecular gas being compressed and fragmented by shocks in the outflow. Alternatively, HCN is instead pumped by mid-IR continuum, but we propose that this effect is not strong for the spatially extend...

  2. A search for high-energy gamma-rays from AGN ON+231 with the STACEE-32 detector

    Science.gov (United States)

    Theoret, Claude G.

    The Solar Tower Atmospheric Čerenkov Effect Experiment (STACEE) is a ground-based atmospheric Čerenkov telescope constructed to conduct γ- ray astronomy. The STACEE telescope employs the mirrors of the National Solar Thermal Test Facility (NSTTF) to observe γ-rays at a lower energy threshold than the current generation of imaging atmospheric Čerenkov telescopes. A prototype of the telescope was constructed in 1998 which used 32 heliostat mirrors of the NSTTF with a total collection area of ˜1200 m 2. This prototype called STACEE-32, was used to search for high energy γ-ray emissions from the active galactic nucleus (AGN) ON + 231 (also known as W Coma and 1219 + 285). The STACEE-32 response as a function of energy was calculated for this source and we report a spectral energy threshold of E th = 130 ± 50GeV. The analysis of data collected in the spring of 1999 resulted in a non-detection of the AGN at this energy. We derived a 95% confidence level upper limit on the integrated γ-ray flux for this source of Φint(E > 130 ± 50GeV) ≤ 2.4 × 10-10 cm-2sec -1. This upper limit further constrains the high energy flux extrapolations of this AGN.

  3. Effect of aluminium on migration of oestrogen unresponsive MDA-MB-231 human breast cancer cells in culture.

    Science.gov (United States)

    Bakir, Ayse; Darbre, Philippa D

    2015-11-01

    Aluminium (Al) has been measured in human breast tissue, and may be a contributory factor in breast cancer development. At the 10th Keele meeting, we reported that long-term exposure to Al could increase migratory properties of oestrogen-responsive MCF-7 human breast cancer cells suggesting a role for Al in the metastatic process. We now report that long-term exposure (20-25 weeks) to Al chloride or Al chlorohydrate at 10(-4) M or 10(-5) M concentrations can also increase the migration of oestrogen unresponsive MDA-MB-231 human breast cancer cells as measured using time-lapse microscopy and xCELLigence technology. In parallel, Al exposure was found to give rise to increased secretion of active matrix metalloproteinase MMP9 as measured by zymography, and increased intracellular levels of activated MMP14 as measured by western immunoblotting. These results demonstrate that Al can increase migration of human breast cancer cells irrespective of their oestrogen responsiveness, and implicate alterations to MMPs as a potential mechanism worthy of further study.

  4. Fluvastatin mediated breast cancer cell death: a proteomic approach to identify differentially regulated proteins in MDA-MB-231 cells.

    Directory of Open Access Journals (Sweden)

    Anantha Koteswararao Kanugula

    Full Text Available Statins are increasingly being recognized as anti-cancer agents against various cancers including breast cancer. To understand the molecular pathways targeted by fluvastatin and its differential sensitivity against metastatic breast cancer cells, we analyzed protein alterations in MDA-MB-231 cells treated with fluvastatin using 2-DE in combination with LC-MS/MS. Results revealed dys-regulation of 39 protein spots corresponding to 35 different proteins. To determine the relevance of altered protein profiles with breast cancer cell death, we mapped these proteins to major pathways involved in the regulation of cell-to-cell signaling and interaction, cell cycle, Rho GDI and proteasomal pathways using IPA analysis. Highly interconnected sub networks showed that vimentin and ERK1/2 proteins play a central role in controlling the expression of altered proteins. Fluvastatin treatment caused proteolysis of vimentin, a marker of epithelial to mesenchymal transition. This effect of fluvastatin was reversed in the presence of mevalonate, a downstream product of HMG-CoA and caspase-3 inhibitor. Interestingly, fluvastatin neither caused an appreciable cell death nor did modulate vimentin expression in normal mammary epithelial cells. In conclusion, fluvastatin alters levels of cytoskeletal proteins, primarily targeting vimentin through increased caspase-3- mediated proteolysis, thereby suggesting a role for vimentin in statin-induced breast cancer cell death.

  5. Integral Field Spectroscopy of Massive, Kiloparsec-Scale Outflows in the Infrared-Luminous QSO Mrk 231

    CERN Document Server

    Rupke, David S N; 10.1088/2041-8205/729/2/L27

    2011-01-01

    The quasi-stellar object (QSO)/merger Mrk 231 is arguably the nearest and best laboratory for studying QSO feedback. It hosts several outflows, including broad-line winds, radio jets, and a poorly-understood kpc scale outflow. In this Letter, we present integral field spectroscopy from the Gemini telescope that represents the first unambiguous detection of a wide-angle, kpc scale outflow from a powerful QSO. Using neutral gas absorption, we show that the nuclear region hosts an outflow with blueshifted velocities reaching 1100 km/s, extending 2-3 kpc from the nucleus in all directions in the plane of the sky. A radio jet impacts the outflow north of the nucleus, accelerating it to even higher velocities (up to 1400 km/s). Finally, 3.5 kpc south of the nucleus, star formation is simultaneously powering an outflow that reaches more modest velocities of only 570 km/s. Blueshifted ionized gas is also detected around the nucleus at lower velocities and smaller scales. The mass and energy flux from the outflow are ...

  6. Cantharidin suppressed breast cancer MDA-MB-231 cell growth and migration by inhibiting MAPK signaling pathway

    Directory of Open Access Journals (Sweden)

    X.-D. Gu

    Full Text Available As an active constituent of the beetle Mylabris used in traditional Chinese medicine, cantharidin is a potent and selective inhibitor of protein phosphatase 2A (PP2A that plays a crucial role in cell cycle progression, apoptosis, and cell fate. The role and possible mechanisms exerted by cantharidin in cell growth and metastasis of breast cancer were investigated in this study. Cantharidin was found to inhibit cell viability and clonogenic potential in a time- and dose-dependent manner. Cell cycle analysis revealed that cell percentage in G2/M phase decreased, whereas cells in S and G1 phases progressively accumulated with the increasing doses of cantharidin treatment. In a xenograft model of breast cancer, cantharidin inhibited tumor growth in a dose-dependent manner. Moreover, high doses of cantharidin treatment inhibited cell migration in wound and healing assay and downregulated protein levels of major matrix metalloproteinases (MMP-2 and MMP-9. MDA-MB-231 cell migration and invasion were dose-dependently inhibited by cantharidin treatment. Interestingly, the members of the mitogen-activated protein kinase (MAPK signaling family were less phosphorylated as the cantharidin dose increased. Cantharidin was hypothesized to exert its anticancer effect through the MAPK signaling pathway. The data of this study also highlighted the possibility of using PP2A as a therapeutic target for breast cancer treatment.

  7. Mitochondrial calcium uniporter silencing potentiates caspase-independent cell death in MDA-MB-231 breast cancer cells.

    Science.gov (United States)

    Curry, Merril C; Peters, Amelia A; Kenny, Paraic A; Roberts-Thomson, Sarah J; Monteith, Gregory R

    2013-05-10

    The mitochondrial calcium uniporter (MCU) transports free ionic Ca(2+) into the mitochondrial matrix. We assessed MCU expression in clinical breast cancer samples using microarray analysis and the consequences of MCU silencing in a breast cancer cell line. Our results indicate that estrogen receptor negative and basal-like breast cancers are characterized by elevated levels of MCU. Silencing of MCU expression in the basal-like MDA-MB-231 breast cancer cell line produced no change in proliferation or cell viability. However, distinct consequences of MCU silencing were seen on cell death pathways. Caspase-dependent cell death initiated by the Bcl-2 inhibitor ABT-263 was not altered by MCU silencing; whereas caspase-independent cell death induced by the calcium ionophore ionomycin was potentiated by MCU silencing. Measurement of cytosolic Ca(2+) levels showed that the promotion of ionomycin-induced cell death by MCU silencing occurs independently of changes in bulk cytosolic Ca(2+) levels. This study demonstrates that MCU overexpression is a feature of some breast cancers and that MCU overexpression may offer a survival advantage against some cell death pathways. MCU inhibitors may be a strategy to increase the effectiveness of therapies that act through the induction of caspase-independent cell death pathways in estrogen receptor negative and basal-like breast cancers.

  8. Inhibition of Hypoxia-Induced Cell Motility by p16 in MDA-MB-231 Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Liyuan Li, Yi Lu

    2010-01-01

    Full Text Available Our previous studies indicated that p16 suppresses breast cancer angiogenesis and metastasis, and downregulates VEGF gene expression by neutralizing the transactivation of the VEGF transcriptional factor HIF-1α. Hypoxia stimulates tumor malignant progression and induces HIF-1α. Because p16 neutralizes effect of HIF-1α and attenuates tumor metastatic progression, we intended to investigate whether p16 directly affects one or more aspects of the malignant process such as adhesion and migration of breast cancer cells. To approach this aim, MDA-MB-231 and other breast cancer cells stably transfected with Tet-on inducible p16 were used to study the p16 effect on growth, adhesion and migration of the cancer cells. We found that p16 inhibits breast cancer cell proliferation and migration, but has no apparent effect on cell adhesion. Importantly, p16 inhibits hypoxia-induced cell migration in breast cancer in parallel with its inhibition of HIF-1α transactivation activity. This study suggests that p16's ability to suppress tumor metastasis may be partially resulted from p16's inhibition on cell migration, in addition to its known functions on inhibition of cell proliferation, angiogenesis and induction of apoptosis.

  9. Optimization of Culture Conditions and Inducers for Improved Protease Production by Penicillium griseofulvum LCJ231 under Submerged Fermentation

    Directory of Open Access Journals (Sweden)

    X. Josephine Jenitta

    2015-04-01

    Full Text Available The production of protease by Penicillium griseofulvum LCJ231 under submerged fermentation was studied with an objective to improve the production through medium optimization. Important nutritional and physical parameters were optimized for maximizing the protease production. The most suitable carbon source, nitrogen source and inducer for maximizing the protease production were studied. It was found that starch, yeast extract and casein were the suitable carbon source, nitrogen source and inducer respectively. The present study also explored the utilization of several agro-wastes as low-cost natural inducers for protease production. The addition of black gram husk as an inducer successfully enhanced the protease production (145.12 U/mL. Maximum production of the protease enzyme was found in the culture medium with initial medium pH of 8 and 2 g/L of inoculum. The results obtained in the present study demonstrate the potential use of the cheap and abundantly available black gram husk for the induction of proteases and thus offer a new approach for industrial enzyme production.

  10. Performance Evaluation of AODV, DSR, DYMO & ZRP in Cost 231 Walfisch-Ikegami Path Loss Propagation Model

    Directory of Open Access Journals (Sweden)

    Rachit JAIN

    2011-07-01

    Full Text Available A Mobile Ad hoc NETwork is a kind of wireless ad-hoc network, and is a self configuring network of mobile routers connected by wireless links. Mobile Ad-Hoc Network (MANET is a wireless network without infrastructure. Self configurability and easy deployment feature of the MANET resulted in numerous applications in this modern era. Efficient routing protocols will make MANETs reliable. Various research communities are working in field of MANET and trying to adopt the protocols and technology in other applications as well. In this work, we present investigations on the behavior of various routing protocol of MANET with a Cost 231 Walfisch-Ikegami Propagation Model. We evaluate the performance of four different ad-hoc routing protocols on four performance metrics such as Average Jitter, Average End-to-End Delay, Throughput, and Packet Delivery Fraction with varying Pause Time. From the simulation results it is concluded that DSR is better in transmission of packets per unit time and maximum number of packets reached their destination successfully with some delays, i.e. PDF & Throughput is more and Average jitter & end-to-end delay is less. Whereas AODV & ZRP having almost same values in all of the performance metrics, they transmit packets with very less delay but transmits less packets to their destination as compare to DSR

  11. A nationwide study of Vipera berus bites during one year-epidemiology and morbidity of 231 cases.

    Science.gov (United States)

    Karlson-Stiber, Christine; Salmonson, Heléne; Persson, Hans

    2006-01-01

    To describe clinical course, influence of treatment, and epidemiology of Vipera berus envenomation in a defined population, and to compare the results with those of a similar, nationwide study in 1975. Design. Retrospective case review study. Case records regarding all patients treated in Swedish hospitals during 1995 for bites by the common European adder, V. berus, were studied. A severity grading was applied. Possible dropout was fewer than 10 patients. A total of 231 inpatients were treated for V. berus bites in Sweden in 1995. Children less than 10 years old were overrepresented and there was a slight predominance for males. Maximum severity of envenomation was none in 11%, minor in 47%, moderate in 29%, and severe in 13% of the cases. A few patients with initially minor or moderate symptoms eventually met the criteria of severe envenomation. Less commonly reported features were pulmonary edema, generalized plasma leakage, seizures, deep venous thrombosis, compartment syndrome, numbness and paraesthesia, and myocardial infarction. Treatment included antivenom in 42 patients [ovine Fab in 30 and equine F(ab')2 in 12 cases]. Systemic symptoms resolved during or shortly after the antivenom infusion. Extensive edema involving the trunk occurred in 5% of the cases in 1995, whereas 14% of the patients had extensive swelling in 1975. Incidence and other epidemiological data were similar to those 20 years ago, whereas the clinical course was more benign. It seems reasonable to believe that this is due to the introduction of effective antivenoms.

  12. Fluvastatin mediated breast cancer cell death: a proteomic approach to identify differentially regulated proteins in MDA-MB-231 cells.

    Science.gov (United States)

    Kanugula, Anantha Koteswararao; Dhople, Vishnu M; Völker, Uwe; Ummanni, Ramesh; Kotamraju, Srigiridhar

    2014-01-01

    Statins are increasingly being recognized as anti-cancer agents against various cancers including breast cancer. To understand the molecular pathways targeted by fluvastatin and its differential sensitivity against metastatic breast cancer cells, we analyzed protein alterations in MDA-MB-231 cells treated with fluvastatin using 2-DE in combination with LC-MS/MS. Results revealed dys-regulation of 39 protein spots corresponding to 35 different proteins. To determine the relevance of altered protein profiles with breast cancer cell death, we mapped these proteins to major pathways involved in the regulation of cell-to-cell signaling and interaction, cell cycle, Rho GDI and proteasomal pathways using IPA analysis. Highly interconnected sub networks showed that vimentin and ERK1/2 proteins play a central role in controlling the expression of altered proteins. Fluvastatin treatment caused proteolysis of vimentin, a marker of epithelial to mesenchymal transition. This effect of fluvastatin was reversed in the presence of mevalonate, a downstream product of HMG-CoA and caspase-3 inhibitor. Interestingly, fluvastatin neither caused an appreciable cell death nor did modulate vimentin expression in normal mammary epithelial cells. In conclusion, fluvastatin alters levels of cytoskeletal proteins, primarily targeting vimentin through increased caspase-3- mediated proteolysis, thereby suggesting a role for vimentin in statin-induced breast cancer cell death.

  13. Anti-proliferative effect of biogenic gold nanoparticles against breast cancer cell lines (MDA-MB-231 & MCF-7)

    Science.gov (United States)

    K. S., Uma Suganya; Govindaraju, K.; Ganesh Kumar, V.; Prabhu, D.; Arulvasu, C.; Stalin Dhas, T.; Karthick, V.; Changmai, Niranjan

    2016-05-01

    Breast cancer is a major complication in women and numerous approaches are being developed to overcome this problem. In conventional treatments such as chemotherapy and radiotherapy the post side effects cause an unsuitable effect in treatment of cancer. Hence, it is essential to develop a novel strategy for the treatment of this disease. In the present investigation, a possible route for green synthesis of gold nanoparticles (AuNPs) using leaf extract of Mimosa pudica and its anticancer efficacy in the treatment of breast cancer cell lines is studied. The synthesized nanoparticles were found to be effective in killing cancer cells (MDA-MB-231 & MCF-7) which were studied using various anticancer assays (MTT assay, cell morphology determination, cell cycle analysis, comet assay, Annexin V-FITC/PI staining and DAPI staining). Cell morphological analysis showed the changes occurred in cancer cells during the treatment with AuNPs. Cell cycle analysis revealed apoptosis in G0/G1 to S phase. Similarly in Comet assay, there was an increase in tail length in treated cells in comparison with the control. Annexin V-FITC/PI staining assay showed prompt fluorescence in treated cells indicating the translocation of phosphatidylserine from the inner membrane. PI and DAPI staining showed the DNA damage in treated cells.

  14. The monoamine oxidase-A inhibitor clorgyline promotes a mesenchymal-to-epithelial transition in the MDA-MB-231 breast cancer cell line.

    Science.gov (United States)

    Satram-Maharaj, Tamara; Nyarko, Jennifer N K; Kuski, Kelly; Fehr, Kelsey; Pennington, Paul R; Truitt, Luke; Freywald, Andrew; Lukong, Kiven Erique; Anderson, Deborah H; Mousseau, Darrell D

    2014-12-01

    Monoamine oxidase-A (MAO-A) dysfunction has been historically associated with depression. Recently, depression as well as altered MAO-A expression have both been associated with a poor prognosis in cancers, although the mechanism involved remains ambiguous. For example, MAO-A mRNA is repressed across cancers, yet MAO-A protein and levels of serotonin, a substrate of MAO-A implicated in depression, are paradoxically increased in malignancies, including breast cancer. The effect of clorgyline (CLG), a selective inhibitor of MAO-A, on malignant behaviour, expression of transitional markers, and biochemical correlates was examined in two human breast carcinoma cell lines, i.e. the epithelial, oestrogen receptor (ER)-positive MCF-7 cell line and the post-EMT (mesenchymal), ER-negative MDA-MB-231 cell line. CLG exerted little effect on malignant behaviour in MCF-7 cells, but inhibited proliferation and anchorage-independent growth, and increased invasiveness and active migration of MDA-MB-231 cells. CLG induced the expression of the mesenchymal marker vimentin in MCF-7 cells, but not in MDA-MB-231 cells. In contrast, CLG induced the epithelial protein marker E-cadherin in both cell lines, with a more robust effect in MDA-MB-231 cells (where a nuclear E-cadherin signal was also detected). This effect appears to be independent of any canonical Snai1-mediated regulation of E-cadherin mRNA expression. CLG interfered with the β-catenin/[phospho]GSK-3β complex as well as the E-cadherin/β-catenin complex in both cell lines cells, but, again, the effect was more robust in MDA-MB-231 cells. Parallel studies revealed a general lack of effect of CLG on the ER-negative, epithelial Au565 breast cancer cell line. Thus, any effect of CLG on metastatic behaviours appears to rely on the cell's EMT status rather than on the cell's ER status. These data suggest that inactivation of MAO-A triggers a mesenchymal-to-epithelial transition in MDA-MB-231 cells via a non-canonical mechanism

  15. 纳米细菌促进乳腺癌细胞MDA-MB-231凋亡%Nanobacteria promotes apoptosis in breast cancer cell line MDA-MB-231

    Institute of Scientific and Technical Information of China (English)

    刘胜男; 张德纯; 张名均; 郭亚楠; 杨晓容; 许舸

    2013-01-01

    目的 观察纳米细菌(nanobacteria,NB)与纳米羟基磷灰石颗粒(nano hydroxyapatite,nHAP)对乳腺癌MDA-MB-231细胞的影响.方法 实验分为NB组、nHAP组和正常对照组,其中NB组和nHAP组悬液的浓度均为2麦氏浊度(M),正常对照组仅加培养基,与乳腺癌MDA-MB-231细胞共同培养24、48、72 h,通过CCK-8检测其对细胞的毒性作用;培养12、24、48、72 h,取上清,经全自动生化分析仪测定LDH活性;作用72 h,经流式细胞仪(flow cytometry,FCM)测定其凋亡率,透射电镜观察其超微结构的变化情况.结果 CCK-8显示,NB组24、48、72 h对细胞的抑制作用均强于nHAP组和正常对照组,差异有统计学意义(P<0.01);NB组LDH含量在24、48、72 h时均高于正常对照组,差异均有统计学意义(P <0.05);24、48、72 h均高于nHA组,但仅24、48 h有统计学差异(P<0.05).nHAP组LDH活性仅在72 h与正常对照组比较有统计学差异(P <0.01);72 h后NB组细胞凋亡率高于nHAP组,差异有统计学意义(P<0.01);透射电镜下观察,NB组可以看到胞质空泡样变,核固缩以及明显的凋亡小体,nHAP组未见明显异常.结论 NB可以抑制乳腺癌细胞的生长,促进其发生凋亡,其导致细胞凋亡的成分不仅仅是NB羟基磷灰石的外壳,也可能与NB的其他组分或代谢产物有关.

  16. Investigation on dietary of 231 rural pregnant women of Uyghur nationality in Kashi city%喀什市231例维吾尔族农村孕妇膳食调查

    Institute of Scientific and Technical Information of China (English)

    孙春梅; 吐尔逊江·买买提明; 王晓军; 张文娟; 郝婷; 王明霞; 袁帅; 阿扎提古丽·艾合买提; 吐尔洪·买买提

    2011-01-01

    Objective: To understand the dietary structure and intake of nutrients of pregnant women of Uyghur nationality in Kashi city, provide a basis for carrying out nutritional health education in minority regions and promoting the development of bearing and rearing better children of Uyghur nationality in Xinjiang. Methods: A random cluster sampling method was used to select 242 pregnant women from two townships and 1 town for 24 -hour dietary survey. Results: Ineffective questionnaires were rejected, 231 effective questionnaires were obtained, the effective rate was 95.45%; the proportions of protein, adipose and carbohydrate out of total heat energy were 13.66%, 13.51% and 72. 83%, respectively, the proportion of high quality protein out of total intake of protein was 26. 20%, the proportion of animal iron was 13. 75%; the proportions of calcium, iodine, vitamin B1, vitamin B2, folic acid and vitamin C were 30. 70%, 29. 52%, 66. 67%, 60. 59%, 21.83% and 67.55%, respectively. Conclusion: The proportions of the three nutrients producing heat in pregnant dietary are not reasonable, the main lacking nutrients are high quality protein, calcium, iron, iodine, vitamin B1, vitamin B2 and folio acid among local residents, the intake of nutrients should be increased in order to guarantee the health of pregnant women and fetuses effectively.%目的:了解喀什地区维吾尔族孕妇膳食结构和营养素摄入状况,为在少数民族地区进行营养健康教育,促进新疆维吾尔族孕妇优牛优育事业的发展提供依据.方法:采用随机整群抽样的方法,抽取了喀什市8个乡中的2乡1镇共242名孕妇进行24 h膳食调查.结果:剔除无效问卷,获得有效问卷231份,有效率95.45%.孕妇膳食中蛋白质、脂肪、碳水化合物分别占总热能的13.66%、13.51%、72.83%,优质蛋白占蛋白总摄入量的26.20%,动物性铁仅占13.75%,钙、碘、维生素B1、维生索B2、叶酸、维生

  17. K2-31B, a Grazing Transiting Hot Jupiter on a 1.26-day Orbit around a Bright G7V Star

    Science.gov (United States)

    Grziwa, Sascha; Gandolfi, Davide; Csizmadia, Szilard; Fridlund, Malcolm; Parviainen, Hannu; Deeg, Hans J.; Cabrera, Juan; Djupvik, Amanda A.; Albrecht, Simon; Palle, Enric B.; Pätzold, Martin; Béjar, Victor J. S.; Prieto-Arranz, Jorge; Eigmüller, Philipp; Erikson, Anders; Fynbo, Johan P. U.; Guenther, Eike W.; Hatzes, Artie P.; Kiilerich, Amanda; Korth, Judith; Kuutma, Teet; Montañés-Rodríguez, Pilar; Nespral, David; Nowak, Grzegorz; Rauer, Heike; Saario, Joonas; Sebastian, Daniel; Slumstrup, Ditte

    2016-11-01

    We report the discovery of K2-31b, the first confirmed transiting hot Jupiter detected by the K2 space mission. We combined K2 photometry with FastCam lucky imaging and FIES and HARPS high-resolution spectroscopy to confirm the planetary nature of the transiting object and derived the system parameters. K2-31b is a 1.8-Jupiter-mass planet on a 1.26-day orbit around a G7 V star ({M}\\star =0.91 M ⊙, {R}\\star =0.78 R ⊙). The planetary radius is poorly constrained (0.7 < R p < 1.4 R Jup),15 owing to the grazing transit and the low sampling rate of the K2 photometry.16

  18. Indirect Determination of the 230Th(n,f) and 231Th(n,f) Cross Sections for Thorium-Based Nuclear Energy Systems

    Energy Technology Data Exchange (ETDEWEB)

    Stroberg, S.R.; Allmond, J.M.; Angell, C.; Bernstein, L.A.; Bleuel, D.L.; Burke, J.T.; Gibelin, J.; Phair, L.; Scielzo, N.D.; Swanberg, E.; Wiedeking, M.; Norman, E.B.; Goldblum, Bethany

    2009-09-11

    The Surrogate Ratio Method (SRM) was employed in the first experimental determination of the 231Th(n,f) cross section, relative to the 235U(n,f) cross section, over an equivalent neutron energy range of 360 keV to 10 MeV. The 230Th(n,f) cross section was also deduced using the SRM, relative to the 234U(n,f) cross section, over an equivalent neutron energy range of 220 keV to 25 MeV. The desired compound nuclei were populated using (3He,3He) and (3He) reactions on targets of 232Th and 236U and relative fission decay probabilities were measured. The surrogate 230,231Th(n,f) cross sections were compared to cross section evaluations and directly-measured experimental data, where available.

  19. Direct RNA sequencing mediated identification of mRNA localized in protrusions of human MDA-MB-231 metastatic breast cancer cells

    DEFF Research Database (Denmark)

    Jakobsen, Kristine Raaby; Sørensen, Emilie; Brøndum, Karin Kathrine;

    2013-01-01

    Background Protrusions of cancer cells conferrers a vital function for cell migration and metastasis. Protein and RNA localization mechanisms have been extensively examined and shown to play pivotal roles for the functional presence of specific protein components in cancer cell protrusions. Methods...... To describe genome wide RNA localized in protrusions of the metastatic human breast cancer cell line MDA-MB-231 we used Boyden chamber based methodology followed by direct mRNA sequencing. Results In the hereby identified group of protrusion localized mRNA some previously were described to be localized...... exemplified by mRNA for Ras-Related protein 13 (RAB13) and p0071 (Plakophilin-4/PKP4). For other transcripts, exemplified by mRNA for SH3PXD2A/TKS5 and PPFIA1/Liprin-α1, only the corresponding proteins previously were described to have protrusion localization. Finally, a cohort of MDA-MB-231 protrusion...

  20. NuSTAR reveals an intrinsically x-ray weak broad absorption line quasar in the ultraluminous infrared galaxy Markarian 231

    DEFF Research Database (Denmark)

    Teng, Stacy H.; Brandt, W. N.; Harrison, F. A.

    2014-01-01

    We present high-energy (3-30 keV) NuSTAR observations of the nearest quasar, the ultraluminous infrared galaxy (ULIRG) Markarian 231 (Mrk 231), supplemented with new and simultaneous low-energy (0.5-8 keV) data from Chandra. The source was detected, though at much fainter levels than previously......-ionization broad absorption line quasar that is intrinsically X-ray weak. The weak ionizing continuum may explain the lack of mid-infrared [O IV], [Ne V], and [Ne VI] fine-structure emission lines which are present in sources with otherwise similar AGN properties. We argue that the intrinsic X-ray weakness may...

  1. A comparative study of protein patterns of human estrogen receptor positive (MCF-7) and negative (MDA-MB-231) breast cancer cell lines.

    Science.gov (United States)

    Flodrova, Dana; Toporova, Lucia; Macejova, Dana; Lastovickova, Marketa; Brtko, Julius; Bobalova, Janette

    2016-07-01

    In the present study, we analyzed the cell lysates of human tumour cell lines representing two major clinically different types of breast cancer. Our main goal was to show the differences between them on proteomic level. Gel electrophoresis followed by MALDI-TOF MS analysis was used for proteins determination. Exactly 98 proteins were unequivocally identified and 60 of them were expressed differentially between MDA-MB-231 and MCF-7 cell lines. Among the proteins reported here, some well-known breast cancer markers (e.g., annexin A1, annexin A2 and vimentin) were identified in the MDA-MB-231 cell line and thus we were able to distinguish both cell lines sufficiently.

  2. Roles for GP IIb/IIIa and αvβ3 integrins in MDA-MB-231 cell invasion and shear flow-induced cancer cell mechanotransduction.

    Science.gov (United States)

    Zhao, Fenglong; Li, Li; Guan, Liuyuan; Yang, Hong; Wu, Chunhui; Liu, Yiyao

    2014-03-01

    Adhesion of cancer cell to endothelial cells and the subsequent trans-endothelial migration are key steps in hematogenous metastasis. However, the molecular mechanisms of cancer cell/endothelial cell interaction under hemodynamic shear flow and how shear flow-induced cancer cell mechanotransduction are yet to be fully defined. In this study, we identified that the integrins of both platelet glycoprotein IIb/IIIa (GP IIb/IIIa) and αvβ3 were crucial for hematogenous metastasis of human breast carcinoma MDA-MB-231 cells. The cell migration and invasion were studied by using Millicell cell culture insert system. The numbers of invaded MDA-MB-231 cells significantly increased by thrombin-activated platelets and reduced by eptifibatide, a platelet inhibitor. Meanwhile, RGDWE peptides, a specific inhibitor of αvβ3 integrin, also inhibited MDA-MB-231 cell invasion. We further used a parallel-plate flow chamber to investigate MDA-MB-231 cell adhesion under flow conditions. Alike in static condition, the adhesion capability of MDA-MB-231 cells to endothelial monolayer was also significantly affected by GP IIb/IIIa and αvβ3 integrins. The expression of matrix metalloproteinase-2 (MMP-2), MMP-9 and αvβ3 integrin in MDA-MB-231 cells were up-regulated after low shear stress exposure (1.84 dynes/cm(2), 2 h). Moreover, we also demonstrated that low shear stress induced a sustained activation of p85 (a regulatory subunit of PI3K) and Akt. Pre-treating MDA-MB-231 cells with the specific PI3K inhibitor of LY294002 abolished the shear stress induced-Akt activation, and the expression of MMP-2, MMP-9, vascular endothelial growth factor (VEGF) and αvβ3 integrin were also down-regulated. Immunofluorescence assay showed that low shear stress also induced αvβ3 integrin clustering and nuclear factor-κB (NF-κB) activation. Interestingly, shear stress-induced activation of Akt and NF-κB was attenuated by LM609, a specific antibody of αvβ3 integrin. It suggests that αvβ3

  3. An in vitro evaluation of graphene oxide reduced by Ganoderma spp. in human breast cancer cells (MDA-MB-231)

    Science.gov (United States)

    Gurunathan, Sangiliyandi; Han, JaeWoong; Park, Jung Hyun; Kim, Jin Hoi

    2014-01-01

    Background Recently, graphene and graphene-related materials have attracted much attention due their unique properties, such as their physical, chemical, and biocompatibility properties. This study aimed to determine the cytotoxic effects of graphene oxide (GO) that is reduced biologically using Ganoderma spp. mushroom extracts in MDA-MB-231 human breast cancer cells. Methods Herein, we describe a facile and green method for the reduction of GO using extracts of Ganoderma spp. as a reducing agent. GO was reduced without any hazardous chemicals in an aqueous solution, and the reduced GO was characterized using a range of analytical procedures. The Ganoderma extract (GE)-reduced GO (GE-rGO) was characterized by ultraviolet-visible absorption spectroscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, dynamic light scattering, scanning electron microscopy, Raman spectroscopy, and atomic force microscopy. Furthermore, the toxicity of GE-rGO was evaluated using a sequence of assays such as cell viability, lactate dehydrogenase leakage, and reactive oxygen species generation in human breast cancer cells (MDA-MB-231). Results The preliminary characterization of reduction of GO was confirmed by the red-shifting of the absorption peak for GE-rGO to 265 nm from 230 nm. The size of GO and GE-rGO was found to be 1,880 and 3,200 nm, respectively. X-ray diffraction results confirmed that reduction processes of GO and the processes of removing intercalated water molecules and the oxide groups. The surface functionalities and chemical natures of GO and GE-rGO were confirmed using Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy. The surface morphologies of the synthesized graphene were analyzed using high-resolution scanning electron microscopy. Raman spectroscopy revealed single- and multilayer properties of GE-rGO. Atomic force microscopy images provided evidence for the formation of graphene

  4. An in vitro evaluation of graphene oxide reduced by Ganoderma spp. in human breast cancer cells (MDA-MB-231

    Directory of Open Access Journals (Sweden)

    Gurunathan S

    2014-04-01

    Full Text Available Sangiliyandi Gurunathan,1,2 JaeWoong Han,1 Jung Hyun Park,1 Jin Hoi Kim1 1Department of Animal Biotechnology, Konkuk University, Seoul, South Korea; 2GS Institute of Bio and Nanotechnology, Coimbatore, Tamilnadu, India Background: Recently, graphene and graphene-related materials have attracted much attention due their unique properties, such as their physical, chemical, and biocompatibility properties. This study aimed to determine the cytotoxic effects of graphene oxide (GO that is reduced biologically using Ganoderma spp. mushroom extracts in MDA-MB-231 human breast cancer cells. Methods: Herein, we describe a facile and green method for the reduction of GO using extracts of Ganoderma spp. as a reducing agent. GO was reduced without any hazardous chemicals in an aqueous solution, and the reduced GO was characterized using a range of analytical procedures. The Ganoderma extract (GE-reduced GO (GE-rGO was characterized by ultraviolet-visible absorption spectroscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, dynamic light scattering, scanning electron microscopy, Raman spectroscopy, and atomic force microscopy. Furthermore, the toxicity of GE-rGO was evaluated using a sequence of assays such as cell viability, lactate dehydrogenase leakage, and reactive oxygen species generation in human breast cancer cells (MDA-MB-231. Results: The preliminary characterization of reduction of GO was confirmed by the red-shifting of the absorption peak for GE-rGO to 265 nm from 230 nm. The size of GO and GE-rGO was found to be 1,880 and 3,200 nm, respectively. X-ray diffraction results confirmed that reduction processes of GO and the processes of removing intercalated water molecules and the oxide groups. The surface functionalities and chemical natures of GO and GE-rGO were confirmed using Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy. The surface morphologies of the synthesized

  5. ESTRATÉGIAS DE RESPONSABILIDADE SOCIAL CORPORATIVA: UM ESTUDO SOBRE OS 231 CASOS CONCRETOS DO INSTITUTO ETHOS

    Directory of Open Access Journals (Sweden)

    Franciara Maria de Oliveira

    2006-05-01

    Full Text Available Resumo
    Um perfil das estratégias de Responsabilidade Social Corporativa adotadas por empresas no Brasil é o objetivo
    principal deste trabalho. Utilizou-se como universo de estudo os 231 Casos Concretos preenchidos
    espontaneamente pelas empresas filiadas na página web do Instituto Ethos de Empresa e Responsabilidade
    Social (Instituto Ethos. Os casos foram analisados pelo software alemão de análise de dados qualitativos
    denominado Atlas.ti 5.0, sob o enfoque metodológico das seis variáveis adotadas por Kotler e Lee (2005 em
    Corporate Social Responsability: doing the most good for your company and your cause, como estratégias para
    alcançar-se a Responsabilidade Social Corporativa. As estratégias analisadas são: Marketing Social
    Corporativo, Marketing de Causa Social, Patrocínio, Filantropia Estratégica, Voluntariado Corporativo e Ação
    Social Responsável. Percebe-se que a maioria das empresas que divulgaram suas estratégias de
    Responsabilidade Social ainda não tem a percepção plena da utilização dessas estratégias, haja vista que a
    grande maioria ainda está classificada com Ação Social Responsável, vindo em seguida o Marketing Social
    Corporativo, Filantropia Estratégica, Voluntariado Corporativo, Patrocínio e Marketing de Causa Social
    Palavras-chave: Estratégias. Marketing. Responsabilidade Social Corporativa.


    Abstract
    A profile of the strategies of Corporate Social Responsibility adopted by companies in Brazil is the main objective
    of this work. It was used as study universe the 231 Concrete Cases filled of spontaneous form for the
    companies registered in the web page of the Ethos Institute of Company and Social Responsibility (Ethos
    Institute. The cases had been analyzed by the German software of analysis of qualitative data called Atlas.ti
    5.0, under the

  6. Comment: 231 [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available 1.png Hideko Urushihara (University of Tsukuba) licensed under CC Attribution2.1 Japan 写真提供:漆原秀子 (筑波大学) Phot...ograph provided by Hideko Urushihara (University of Tsukuba) bando 2010/08/04 09:34:01 2010/08/04 09:45:10 ...

  7. Down-Regulation of Notchl and NF-κB by Curcumin in Breast Cancer Cells MDA-MB-231

    Institute of Scientific and Technical Information of China (English)

    LONG Li; CAO You-de

    2008-01-01

    Objective:To test whether the down-regulation of Notch1 gene expression by curcumin could inhibit cell growth and induce apoptosis,which may be associated mechanistically with the down-regulation of NF-κB in breast cancer cells. Methods:Breast cancer cell lines MDA-MB-231 were cultured in vitro and treated with different dosages of curcumin(0,1.25,5.0,20.0μmol/L)for dose-dependent assay and different time(0,24,48,72 h)at the dosage of 5.0μmol/L for time course assay.The changes of the mRNA and protein expression of Notch1 and NF-κB were measured by RT-PCR and Western Blot,and MTT assay was used to measure the change of proliferation. Results:The mRNA and protein levels of Notch 1 and NF-κB were decreased significantly in human breast cancer cell line with the increase of dosage of curcumin(P<0.05),and with the extension of time course(P<0.05).These changes suggested a dose- and time-dependent manner.The proliferation rate of cells also was significantly inhibited(P<0.05). Conclusion:The current results show that the Notch-1 signaling pathway is associated mechanistically with NF-κB activity during curcumin-induced cell growth inhibition and apoptosis of breast cancer cells.These results suggest that the down-regulation of Notch signaling by curcumin may be a novel strategy for the treatment of patients with breast cancer.

  8. Frequent loss of heterozygosity in two distinct regions,8p23.1 and 8p22,in hepatocelluar carcinoma

    Institute of Scientific and Technical Information of China (English)

    Tomoe Lu; Hiroshi Hano; Chenxi Meng; Keisuke Nagatsuma; Satoru Chiba; Masahiro Ikegami

    2007-01-01

    AIM:To identify the precise location of putative tumor suppressor genes(TSGs)on the short arm of chromosome 8 in patients with hepatocellular carcinoma(HCC).METHODS:We used 16 microsatellite markers informative in Japanese patients,which were selected from 61 published markers,on 8p,to analyze the frequency of loss of heterozygosity(LOH)in each region in 33 cases(56 lesions)of HCC.RESULTS:The frequency of LOH at 8p23.2-21 with at least one marker was 63%(20/32)in the informative cases.More specifically,the frequency of LOH at 8p23.2,8p23.1,8p22,and 8p21 was 6%,52%,47%,and 13% in HCC cases.The LOH was significantly more frequent at 8p23.1 and 8p22 than the average(52% vs 22%,P = 0.0008;and 47% vs 22%,P = 0.004,respectively)or others sites,such as 8p23.2(52% vs 6%,P = 0.003;47% vs 22%,P = 0.004)and 8p21(52% vs 13%,P = 0.001;47% vs 13%,P = 0.005)in liver cancer on the basis of cases.Notably,LOH frequency was significantly higher at D8S277,D8S503,D8S1130,D8S552,D8S254 and D8S258 than at the other sites.However,no allelic loss was detected at any marker on 8p in the lesions of nontumor liver tissues.CONCLUSION:Deletion of 8p,especially the loss of 8p23.1-22,is an important event in the initiation or promotion of HCC.Our results should be useful in identifying critical genes that might lie at 8p23.1-22.

  9. Genetic variation in Przewalski's horses, with special focus on the last wild caught mare, 231 Orlitza III.

    Science.gov (United States)

    Bowling, A T; Zimmermann, W; Ryder, O; Penado, C; Peto, S; Chemnick, L; Yasinetskaya, N; Zharkikh, T

    2003-01-01

    In our continuing efforts to document genetic diversity in Przewalski's horses and relatedness with domestic horses, we report genetic variation at 22 loci of blood group and protein polymorphisms and 29 loci of DNA (microsatellite) polymorphisms. The loci have been assigned by linkage or synteny mapping to 20 autosomes and the X chromosome of the domestic horse (plus four loci unassigned to a chromosome). With cumulative data from tests of 568 Przewalski's horses using blood, hair or tooth samples, no species-defining markers were identified, however a few markers were present in the wild species but not in domestic horses. Inheritance patterns and linkage relationships reported in domestic horses appeared to be conserved in Przewalski's horses. A derived type for the last wild caught mare 231 Orlitza III provided evidence for markers apparently not found in (or not currently available by descent from) the other species founders that were captured at the end of the nineteenth century. This information has been critical to the development of parentage analyses in the studbook population of Przewalski's horses at Askania Nova, at one time the largest herd of captive animals and the source of stock for reintroduction efforts. Some horses in the study showed genetic incompatibilities with their sire or dam, contradicting published studbook information. In many cases alternative parentage could be assigned from living animals. To assist in identification of correct parentage, DNA marker types for deceased horses were established from archived materials (teeth) or derived from offspring. Genetic markers were present in pedigreed animals whose origin could not be accounted for from founders. Genetic distance analysis of erythrocyte protein, electrophoretic and microsatellite markers in Przewlaski's horses and ten breeds of domestic horse place the Przewalski's horse as an outgroup to domestic horses, introgression events from domestic horses not withstanding.

  10. Correlation between Slug transcription factor and miR-221 in MDA-MB-231 breast cancer cells

    Directory of Open Access Journals (Sweden)

    Lambertini Elisabetta

    2012-10-01

    Full Text Available Abstract Background Breast cancer and its metastatic progression is mainly directed by epithelial to mesenchymal transition (EMT, a phenomenon supported by specific transcription factors and miRNAs. Methods In order to investigate a possible correlation between Slug transcription factor and miR-221, we performed Slug gene silencing in MDA-MB-231 breast cancer cells and evaluated the expression of genes involved in supporting the breast cancer phenotype, using qRT-PCR and Western blot analysis. Chromatin immunoprecipitation and wound healing assays were employed to determine a functional link between these two molecules. Results We showed that Slug silencing significantly decreased the level of miR-221 and vimentin, reactivated Estrogen Receptor α and increased E-cadherin and TRPS1 expression. We demonstrated that miR-221 is a Slug target gene, and identified a specific region of miR-221 promoter that is transcriptionally active and binds the transcription factor Slug “in vivo”. In addition, we showed that in Slug-silenced cells, wich retained residual miR-221 (about 38%, cell migration was strongly inhibited. Cell migration was inhibited, but to a less degree, following complete knockdown of miR-221 expression by transfection with antagomiR-221. Conclusions We report for the first time evidence of a correlation between Slug transcription factor and miR-221 in breast cancer cells. These studies suggest that miR-221 expression is, in part, dependent on Slug in breast cancer cells, and that Slug plays a more important role than miR-221 in cell migration and invasion.

  11. Mitochondrial calcium uniporter silencing potentiates caspase-independent cell death in MDA-MB-231 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Curry, Merril C.; Peters, Amelia A. [School of Pharmacy, The University of Queensland, Brisbane, Queensland 4072 (Australia); Kenny, Paraic A. [Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Roberts-Thomson, Sarah J. [School of Pharmacy, The University of Queensland, Brisbane, Queensland 4072 (Australia); Monteith, Gregory R., E-mail: gregm@uq.edu.au [School of Pharmacy, The University of Queensland, Brisbane, Queensland 4072 (Australia)

    2013-05-10

    Highlights: •Some clinical breast cancers are associated with MCU overexpression. •MCU silencing did not alter cell death initiated with the Bcl-2 inhibitor ABT-263. •MCU silencing potentiated caspase-independent cell death initiated by ionomycin. •MCU silencing promoted ionomycin-mediated cell death without changes in bulk Ca{sup 2+}. -- Abstract: The mitochondrial calcium uniporter (MCU) transports free ionic Ca{sup 2+} into the mitochondrial matrix. We assessed MCU expression in clinical breast cancer samples using microarray analysis and the consequences of MCU silencing in a breast cancer cell line. Our results indicate that estrogen receptor negative and basal-like breast cancers are characterized by elevated levels of MCU. Silencing of MCU expression in the basal-like MDA-MB-231 breast cancer cell line produced no change in proliferation or cell viability. However, distinct consequences of MCU silencing were seen on cell death pathways. Caspase-dependent cell death initiated by the Bcl-2 inhibitor ABT-263 was not altered by MCU silencing; whereas caspase-independent cell death induced by the calcium ionophore ionomycin was potentiated by MCU silencing. Measurement of cytosolic Ca{sup 2+} levels showed that the promotion of ionomycin-induced cell death by MCU silencing occurs independently of changes in bulk cytosolic Ca{sup 2+} levels. This study demonstrates that MCU overexpression is a feature of some breast cancers and that MCU overexpression may offer a survival advantage against some cell death pathways. MCU inhibitors may be a strategy to increase the effectiveness of therapies that act through the induction of caspase-independent cell death pathways in estrogen receptor negative and basal-like breast cancers.

  12. Human ether à-gogo K(+) channel 1 (hEag1) regulates MDA-MB-231 breast cancer cell migration through Orai1-dependent calcium entry.

    Science.gov (United States)

    Hammadi, Mehdi; Chopin, Valérie; Matifat, Fabrice; Dhennin-Duthille, Isabelle; Chasseraud, Maud; Sevestre, Henri; Ouadid-Ahidouch, Halima

    2012-12-01

    Breast cancer (BC) has a poor prognosis due to its strong metastatic ability. Accumulating data present ether à go-go (hEag1) K(+) channels as relevant player in controlling cell cycle and proliferation of non-invasive BC cells. However, the role of hEag1 in invasive BC cells migration is still unknown. In this study, we studied both the functional expression and the involvement in cell migration of hEag1 in the highly metastatic MDA-MB-231 human BC cells. We showed that hEag1 mRNA and proteins were expressed in human invasive ductal carcinoma tissues and BC cell lines. Functional activity of hEag1 channels in MDA-MB-231 cells was confirmed using astemizole, a hEag1 blocker, or siRNA. Blocking or silencing hEag1 depolarized the membrane potential and reduced both Ca(2+) entry and MDA-MB-231 cell migration without affecting cell proliferation. Recent studies have reported that Ca(2+) entry through Orai1 channels is required for MDA-MB-231 cell migration. Down-regulation of hEag1 or Orai1 reduced Ca(2+) influx and cell migration with similar efficiency. Interestingly, no additive effects on Ca(2+) influx or cell migration were observed in cells co-transfected with sihEag1 and siOrai1. Finally, both Orai1 and hEag1 are expressed in invasive breast adenocarcinoma tissues and invaded metastatic lymph node samples (LNM(+)). In conclusion, this study is the first to demonstrate that hEag1 channels are involved in the serum-induced migration of BC cells by controlling the Ca(2+) entry through Orai1 channels. hEag1 may therefore represent a potential target for the suppression of BC cell migration, and thus prevention of metastasis development.

  13. Polyamines modulate the roscovitine-induced cell death switch decision autophagy vs. apoptosis in MCF-7 and MDA-MB-231 breast cancer cells.

    Science.gov (United States)

    Arisan, Elif Damla; Akkoç, Yunus; Akyüz, Kaan Gencer; Kerman, Ezgi Melek; Obakan, Pinar; Çoker-Gürkan, Ajda; Palavan Ünsal, Narçin

    2015-06-01

    Current clinical strategies against breast cancer mainly involve the use of anti‑hormonal agents to decrease estrogen production; however, development of resistance is a major problem. The resistance phenotype depends on the modulation of cell‑cycle regulatory proteins, cyclins and cyclin‑dependent kinases. Roscovitine, a selective inhibitor of cyclin‑dependent kinases, shows high therapeutic potential by causing cell‑cycle arrest in various cancer types. Autophagy is a type of cell death characterized by the enzymatic degradation of macromolecules and organelles in double‑ or multi‑membrane autophagic vesicles. This process has important physiological functions, including the degradation of misfolded proteins and organelle turnover. Recently, the switch between autophagy and apoptosis has been proposed to constitute an important regulator of cell death in response to chemotherapeutic drugs. The process is regulated by several proteins, such as the proteins of the Atg family, essential for the initial formation of the autophagosome, and PI3K, important at the early stages of autophagic vesicle formation. Polyamines (PAs) are small aliphatic amines that play major roles in a number of eukaryotic processes, including cell proliferation. The PA levels are regulated by ornithine decarboxylase (ODC), the rate‑limiting enzyme in PA biosynthesis. In this study, we aimed to investigate the role of PAs in roscovitine‑induced autophagic/apoptotic cell death in estrogen receptor‑positive MCF‑7 and estrogen receptor‑negative MDA‑MB‑231 breast cancer cells. We show that MDA‑MB‑231 cells are more resistant to roscovitine than MCF‑7 cells. This difference was related to the regulation of autophagic key molecules in MDA‑MB‑231 cells. In addition, we found that exogenous PAs have a role in the cell death decision between roscovitine‑induced apoptosis or autophagy in MCF‑7 and MDA‑MB‑231 breast cancer cells.

  14. Phenotypic and Molecular Convergence of 2q23.1 Deletion Syndrome with Other Neurodevelopmental Syndromes Associated with Autism Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    Sureni V. Mullegama

    2015-04-01

    Full Text Available Roughly 20% of autism spectrum disorders (ASD are syndromic with a well-established genetic cause. Studying the genes involved can provide insight into the molecular and cellular mechanisms of ASD. 2q23.1 deletion syndrome (causative gene, MBD5 is a recently identified genetic neurodevelopmental disorder associated with ASD. Mutations in MBD5 have been found in ASD cohorts. In this study, we provide a phenotypic update on the prevalent features of 2q23.1 deletion syndrome, which include severe intellectual disability, seizures, significant speech impairment, sleep disturbance, and autistic-like behavioral problems. Next, we examined the phenotypic, molecular, and network/pathway relationships between nine neurodevelopmental disorders associated with ASD: 2q23.1 deletion Rett, Angelman, Pitt-Hopkins, 2q23.1 duplication, 5q14.3 deletion, Kleefstra, Kabuki make-up, and Smith-Magenis syndromes. We show phenotypic overlaps consisting of intellectual disability, speech delay, seizures, sleep disturbance, hypotonia, and autistic-like behaviors. Molecularly, MBD5 possibly regulates the expression of UBE3A, TCF4, MEF2C, EHMT1 and RAI1. Network analysis reveals that there could be indirect protein interactions, further implicating function for these genes in common pathways. Further, we show that when MBD5 and RAI1 are haploinsufficient, they perturb several common pathways that are linked to neuronal and behavioral development. These findings support further investigations into the molecular and pathway relationships among genes linked to neurodevelopmental disorders and ASD, which will hopefully lead to common points of regulation that may be targeted toward therapeutic intervention.

  15. 49 CFR 231.24 - Box and other house cars with roofs, 16 feet 10 inches or more above top of rail. 1

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Box and other house cars with roofs, 16 feet 10... APPLIANCE STANDARDS § 231.24 Box and other house cars with roofs, 16 feet 10 inches or more above top of.... Same as specified for “Box and Other House Cars.” (2) Dimensions. Same as specified for “Box and...

  16. Estrogenic Activity of Some Phytoestrogens on Bovine Oxytocin and Thymidine Kinase-ERE Promoter through Estrogen Receptor-α in MDA-MB 231 Cells

    OpenAIRE

    Ehsan Zayerzadeh; Mohammad Kazem Koohi; Azadeh Fardipour

    2014-01-01

    Background: Phytoestrogens, a group of plant-derived polyphenolic compounds have recently come into considerable attention due to the increasing information on their potential adverse effects in human health. Some of phytoestrogens show estrogenic activity that may be carcinogenic for human. In the present study, we investigated the transcriptional effects of variety of phytoestrogens on the bovine oxytocin and the thymidine kinase-ERE promoter by estrogen receptor α in MDA-MB 231 breast canc...

  17. High-resolution fission cross section of 231Pa. [0. 4 eV to 12 MeV

    Energy Technology Data Exchange (ETDEWEB)

    Plattard, S.; Auchampaugh, G. F.; Hill, N. W.; de Saussure, G.; Perez, R. B.; Harvey, J. A.

    1979-01-01

    The /sup 231/Pa fission cross section was measured with high resolution at OREA from 0.1 to 12 MeV and between 0.4 eV and 10 keV. The data show evidence for fractionated vibrational structures in the threshold region of the fission cross section, and narrow fission resonances above 0.4 eV with an average fission width < GAMMA/sub f/ > = 8 ..mu..eV. 3 figures, 3 tables.

  18. G-231A and G+70C polymorphisms of endothelin receptor type-A gene could affect the psoriasis area and severity index score and endothelin 1 levels

    Directory of Open Access Journals (Sweden)

    Gökhan Okan

    2015-01-01

    Full Text Available Background: The etiopathogenesis of psoriasis has not been clearly elucidated although the role of chronic inflammation, imbalance between pro- and anti-inflammatory cytokines, and many immunological events have been established. Endothelin 1 (EDN1 and endothelin receptor type-A (EDNRA are implicated in the inflammatory process. The relationships between EDN1 and EDNRA polymorphisms with several diseases have been found. Aims and Objectives: This study examined the possible association of EDN1 (G5665T and T-1370G and EDNRA (G-231A and G + 70C single nucleotide polymorphisms (SNPs with the occurence of psoriasis, and evaluated the relationship between genotypes and clinical/laboratory manifestation of psoriasis. Materials and Methods: We analyzed genotype and allele distributions of the above-mentioned polymorphisms in 151 patients with psoriasis and 152 healthy controls by real-time PCR combined with melting curve analysis. Results: We did not find significant differences in the genotype and allele distributions of EDN1 T-1370G, EDNRA G-231A, and EDNRA G+70C polymorphisms between patients with psoriasis and healthy controls. Psoriasis area and severity index (PASI score of EDNRA -231 polymorphic A allele carrying subjects (AA and AA + AG was higher than that of wild homozygotes (P = 0.044 and P = 0.027, respectively. In addition, EDN1 levels in EDNRA+70 polymorphic C allele carriers (CC + CG were elevated when compared with GG genotype; however, the difference was at borderline significance (P = 0.05. Conclusion: Although there were no associations between studied polymorphisms and psoriasis susceptibility, the PASI score and EDN1 levels seem to be affected by EDNRA G-231A and G + 70C polymorphisms.

  19. ST6GalNAc I expression in MDA-MB-231 breast cancer cells greatly modifies their O-glycosylation pattern and enhances their tumourigenicity.

    Science.gov (United States)

    Julien, S; Adriaenssens, E; Ottenberg, K; Furlan, A; Courtand, G; Vercoutter-Edouart, A-S; Hanisch, F-G; Delannoy, P; Le Bourhis, X

    2006-01-01

    Sialyl-Tn is a carbohydrate antigen overexpressed in several epithelial cancers, including breast cancer, and usually associated with poor prognosis. Sialyl-Tn is synthesized by a CMP-Neu5Ac:GalNAcalpha2,6-sialyltransferase: CMP-Neu5Ac: R-GalNAcalpha1-O-Ser/Thr alpha2,6-sialyltransferase (EC 2.4.99.3) (ST6GalNAc I), which transfers a sialic acid residue in alpha2,6-linkage to the GalNAcalpha1-O-Ser/Thr structure. However, established breast cancer cell lines express neither ST6GalNAc I nor sialyl-Tn. We have previously shown that stable transfection of MDA-MB-231, a human breast cancer cell line, with ST6GalNAc I cDNA induces sialyl-Tn antigen (STn) expression. We report here the modifications of the O-glycosylation pattern of a MUC1-related recombinant protein secreted by MDA-MB-231 sialyl-Tn positive cells. We also show that sialyl-Tn expression and concomitant changes in the overall O-glycan profiles induce a decrease of adhesion and an increase of migration of MDA-MB-231. Moreover, STn positive clones exhibit an increased tumour growth in severe combined immunodeficiency (SCID) mice. These observations suggest that modification of the O-glycosylation pattern induced by ST6GalNAc I expression are sufficient to enhance the tumourigenicity of MDA-MB-231 breast cancer cells.

  20. Identification of Novel Human Breast Carcinoma (MDA-MB-231 Cell Growth Modulators from a Carbohydrate-Based Diversity Oriented Synthesis Library

    Directory of Open Access Journals (Sweden)

    Elena Lenci

    2016-10-01

    Full Text Available The application of a cell-based growth inhibition on a library of skeletally different glycomimetics allowed for the selection of a hexahydro-2H-furo[3,2-b][1,4]oxazine compound as candidate inhibitors of MDA-MB-231 cell growth. Subsequent synthesis of analogue compounds and preliminary biological studies validated the selection of a valuable hit compound with a novel polyhydroxylated structure for the modulation of the breast carcinoma cell cycle mechanism.

  1. Identification of Novel Human Breast Carcinoma (MDA-MB-231) Cell Growth Modulators from a Carbohydrate-Based Diversity Oriented Synthesis Library.

    Science.gov (United States)

    Lenci, Elena; Innocenti, Riccardo; Biagioni, Alessio; Menchi, Gloria; Bianchini, Francesca; Trabocchi, Andrea

    2016-10-20

    The application of a cell-based growth inhibition on a library of skeletally different glycomimetics allowed for the selection of a hexahydro-2H-furo[3,2-b][1,4]oxazine compound as candidate inhibitors of MDA-MB-231 cell growth. Subsequent synthesis of analogue compounds and preliminary biological studies validated the selection of a valuable hit compound with a novel polyhydroxylated structure for the modulation of the breast carcinoma cell cycle mechanism.

  2. Effects of exosomes derived from MDA-MB-231 on proliferation of endothelial cells and the role of MAPK/ERK and PI3K/Akt pathways

    Directory of Open Access Journals (Sweden)

    Shuang LONG

    2012-11-01

    Full Text Available Objective  To investigate the effects of exosomes derived from breast cancer cell line MDA-MB-231 on proliferation of human umbilical cord vein endothelial cells (HUVECs, and evaluate the role of MAPK/ERK and PI3K/Akt signal transduction pathway during the process. Methods  Exosomes were derived and purified from MDA-MB-231 by cryogenic ultracentrifugation and density gradient centrifugation. MTT assay was carried out for measurement of cell proliferation in HUVECs with exosome of 50, 100, 200 and 400μg/ml. The states of cell cycle of HUVECs co-cultured with 200μg/ml exosomes were detected by flow cytometry. The effects of 200μg/ml exosomes on the expression of ERK, Akt and phosphorylated ERK, Akt in HUVECs were detected with Western blotting. Results  Exosomes derived from MDA-MB-231 significantly promoted HUVECs proliferation in a classical time-and dose-dependent manner. Flow cytometry revealed that, co-cultured with 200μg/ml exosomes for 24h, S-phase cells in HUVECs increased, while G1/S phase cells in HUVECs decreased. Western blotting showed that, cocultured with 200μg/ml exosomes for 24h, 48h and 72h, the expressions of phosphorylated ERK and Akt were up-regulated in a time-dependent manner. Conclusion  Exosomes derived from breast cancer cell line MDA-MB-231 may promote HUVECs proliferation, the changes in cell cycle and the continuous activation of the MAPK/ERK and PI3K/Akt signal transduction pathways may be the underlying mechanism.

  3. Mouse model reveals the role of SOX7 in the development of congenital diaphragmatic hernia associated with recurrent deletions of 8p23.1

    Science.gov (United States)

    Wat, Margaret J.; Beck, Tyler F.; Hernández-García, Andrés; Yu, Zhiyin; Veenma, Danielle; Garcia, Monica; Holder, Ashley M.; Wat, Jeanette J.; Chen, Yuqing; Mohila, Carrie A.; Lally, Kevin P.; Dickinson, Mary; Tibboel, Dick; de Klein, Annelies; Lee, Brendan; Scott, Daryl A.

    2012-01-01

    Recurrent microdeletions of 8p23.1 that include GATA4 and SOX7 confer a high risk of both congenital diaphragmatic hernia (CDH) and cardiac defects. Although GATA4-deficient mice have both CDH and cardiac defects, no humans with cardiac defects attributed to GATA4 mutations have been reported to have CDH. We were also unable to identify deleterious GATA4 sequence changes in a CDH cohort. This suggested that haploinsufficiency of another 8p23.1 gene may contribute, along with GATA4, to the development of CDH. To determine if haploinsufficiency of SOX7—another transcription factor encoding gene—contributes to the development of CDH, we generated mice with a deletion of the second exon of Sox7. A portion of these Sox7Δex2/+ mice developed retrosternal diaphragmatic hernias located in the anterior muscular portion of the diaphragm. Anterior CDH is also seen in Gata4+/− mice and has been described in association with 8p23.1 deletions in humans. Immunohistochemistry revealed that SOX7 is expressed in the vascular endothelial cells of the developing diaphragm and may be weakly expressed in some diaphragmatic muscle cells. Sox7Δex2/Δex2 embryos die prior to diaphragm development with dilated pericardial sacs and failure of yolk sac remodeling suggestive of cardiovascular failure. Similar to our experience screening GATA4, no clearly deleterious SOX7 sequence changes were identified in our CDH cohort. We conclude that haploinsufficiency of Sox7 or Gata4 is sufficient to produce anterior CDH in mice and that haploinsufficiency of SOX7 and GATA4 may each contribute to the development of CDH in individuals with 8p23.1 deletions. PMID:22723016

  4. Assessment of 2q23.1 Microdeletion Syndrome Implicates MBD5 as a Single Causal Locus of Intellectual Disability, Epilepsy, and Autism Spectrum Disorder

    OpenAIRE

    Talkowski, Michael E.; Mullegama, Sureni V.; Rosenfeld, Jill A.; van Bon, Bregje W.M.; Shen, Yiping; Repnikova, Elena A.; Gastier-Foster, Julie; Thrush, Devon Lamb; Kathiresan, Sekar; Ruderfer, Douglas M.; Chiang, Colby; Hanscom, Carrie; Ernst, Carl; Lindgren, Amelia M.; Morton, Cynthia C.

    2011-01-01

    Persons with neurodevelopmental disorders or autism spectrum disorder (ASD) often harbor chromosomal microdeletions, yet the individual genetic contributors within these regions have not been systematically evaluated. We established a consortium of clinical diagnostic and research laboratories to accumulate a large cohort with genetic alterations of chromosomal region 2q23.1 and acquired 65 subjects with microdeletion or translocation. We sequenced translocation breakpoints; aligned microdele...

  5. Combined xanthorrhizol-curcumin exhibits synergistic growth inhibitory activity via apoptosis induction in human breast cancer cells MDA-MB-231

    Directory of Open Access Journals (Sweden)

    Azimahtol Hawariah

    2009-01-01

    Full Text Available Abstract Background It has been suggested that combined effect of natural products may improve the treatment effectiveness in combating proliferation of cancer cells. The present study was undertaken to evaluate the possibility that the combination of xanthorrhizol and curcumin might show synergistic growth inhibitory effect towards MDA-MB-231 human breast cancer cells via apoptosis induction. The effective dose that produced 50% growth inhibition (GI50 was calculated from the log dose-response curve of fixed-combinations of xanthorrhizol and curcumin generated from the sulforhodamine B (SRB assay. The experimental GI50 value was used to determine the synergistic activity of the combination treatment by isobolographic analysis and combination-index method. Further investigation of mode of cell death induced by the combination treatment was conducted in the present study. Results Isobole analysis revealed that substances interaction was synergistic when xanthorrhizol and curcumin were added concurrently to the cultures but merely additive when they were added sequentially. The synergistic combination treatment was then applied to the cultures to investigate the mode of cell death induced by the treatment. Immunofluorescence staining using antibody MitoCapture™ revealed the possibility of altered mitochondrial transmembrane potential, which is one of the hallmark of apoptosis. Hoechst 33258 nuclear staining assay showed the rate of apoptosis of MDA-MB-231 cells to increase in response to the treatment. Apoptotic cell death was further confirmed by DNA fragmentation assay, where internucleosomal excision of DNA was induced upon treatment with xanthorrhizol-curcumin. Conclusion This is the first time the combined cytotoxic effect of xanthorrhizol and curcumin on MDA-MB-231 cells has been documented and our findings provide experimental support to the hypothesis that combined xanthorrhizol-curcumin showed synergistic growth inhibitory activity on

  6. Inhibition of MMP-3 activity and invasion of the MDA-MB-231 human invasive breast carcinoma cell line by bioflavonoids

    Institute of Scientific and Technical Information of China (English)

    Kanokkarn PHROMNOI; Supachai YODKEEREE; Songyot ANUCHAPREEDA; Pornngarm LIMTRAKUL

    2009-01-01

    Aim: Stromelysin 1 (matrix metalloproteinase 3; MMP-3) is an enzyme known to be involved in tumor invasion and metastasis. In this study, flavonoids from vegetables and fruits, such as quercetin, kaempferol, genistein, genistin, and daidzein, were tested for their abil-ity to modulate the secretion and activity of MMP-3 in the MDA-MB-231 breast cancer cell line. In addition, we investigated the in vitro effects of flavonoids on MDA-MB-231 cell invasion.Methods: The toxic concentration range of flavonoids was evaluated using the MTr assay. The ability of MDA-MB-231 cells to invade was evaluated using a modified Boyden chamber system. The activity of MMP-3 was determined by casein zymography. The secretion of MMP-3 was evaluated using Western blotting, casein zymography and confirmed by ELISA.Results: Some putative flavonoids, ie, quercetin and kaempferol (flavonols), significantly inhibited the in vitro invasion of MDA-MB-231cells in a concentration-dependent manner, with IC50 values of 27 and 30 pmol/L, respectively. Quercetin and kaempferol also reduced MMP-3 activity in a dose-dependent manner, with IC50 values in the range of 30 μmol/L and 45 μmol/L, respectively. None of the flavonoids had a significant effect on the secretion of MMP-3.Conclusion: These data show that the flavonols quercetin and kaempferol have higher anti-invasion potency and higher MMP-3 inhibi-tory activity than isoflavones genistein, genistin and daidzein. In contrast, neither flavonols nor isofiavones have any effect on MMP-3 secretion.

  7. Extracellular vesicles from MDA-MB-231 breast cancer cells stimulated with linoleic acid promote an EMT-like process in MCF10A cells.

    Science.gov (United States)

    Galindo-Hernandez, Octavio; Serna-Marquez, Nathalia; Castillo-Sanchez, Rocio; Salazar, Eduardo Perez

    2014-12-01

    Extracellular vesicles (EVs) are membrane-limited vesicles secreted by normal and malignant cells and their function is dependent on the cargo they carry and the cell type from which they originate. Moreover, EVs mediate many stages of tumor progression including angiogenesis, escape from immune surveillance and extracellular matrix degradation. Linoleic acid (LA) is an essential polyunsaturated fatty acid that induces expression of plasminogen activator inhibitor-1, proliferation, migration and invasion in breast cancer cells. However the role of secreted EVs from MDA-MB-231 cells stimulated with LA like mediator of the epithelial-mesenchymal-transition (EMT) process in mammary non-tumorigenic epithelial cells MCF10A remains to be studied. In the present study, we demonstrate that treatment of MDA-MB-231 cells for 48 h with 90 µM LA does not induce an increase in the number of secreted EVs. In addition, EVs isolated from supernatants of MDA-MB-231 stimulated for 48 h with 90 µM LA induce a transient down-regulation of E-cadherin expression, and an increase of Snail1 and 2, Twist1 and 2, Sip1, vimentin and N-cadherin expression in MCF10A cells. EVs also promote an increase of MMP-2 and -9 secretions, an increase of NFκB-DNA binding activity, migration and invasion in MCF10A cells. In summary, our findings demonstrate, for the first time, that EVs isolated from supernatants of MDA-MB-231 stimulated for 48 h with 90 µM LA induce an EMT-like process in MCF10A cells.

  8. A Breast Cell Atlas: Organelle analysis of the MDA-MB-231 cell line by density-gradient fractionation using isotopic marking and label-free analysis

    Directory of Open Access Journals (Sweden)

    Marianne Sandin

    2015-09-01

    Full Text Available Protein translocation between organelles in the cell is an important process that regulates many cellular functions. However, organelles can rarely be isolated to purity so several methods have been developed to analyse the fractions obtained by density gradient centrifugation. We present an analysis of the distribution of proteins amongst organelles in the human breast cell line, MDA-MB-231 using two approaches: an isotopic labelling and a label-free approach.

  9. Enhancement of viability of radiosensitive (PBMC) and resistant (MDA-MB-231) clones in low-dose-rate cobalt-60 radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Falcao, Patricia Lima, E-mail: patricialfalcao@gmail.com [Universidade Federal do Amazonas (UFAM), Manaus, AM (Brazil); Motta, Barbara Miranda; Lima, Fernanda Castro de; Lima, Celso Vieira; Campos, Tarcisio Passos Ribeiro [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil)

    2015-05-15

    Objective: in the present study, the authors investigated the in vitro behavior of radio-resistant breast adenocarcinoma (MDA-MB-231) cells line and radiosensitive peripheral blood mononuclear cells (PBMC), as a function of different radiation doses, dose rates and postirradiation time kinetics, with a view to the interest of clinical radiotherapy. Materials and methods: the cells were irradiated with Co-60, at 2 and 10 Gy and two different exposure rates, 339.56 cGy.min{sup -1} and the other corresponding to one fourth of the standard dose rates, present over a 10-year period of cobalt therapy. Post-irradiation sampling was performed at pre-established kinetics of 24, 48 and 72 hours. The optical density response in viability assay was evaluated and a morphological analysis was performed. Results: radiosensitive PBMC showed decrease in viability at 2 Gy, and a more significant decrease at 10 Gy for both dose rates. MDAMB-231 cells presented viability decrease only at higher dose and dose rate. The results showed MDA-MB-231 clone expansion at low dose rate after 48-72 hours post-radiation. Conclusion: low dose rate shows a possible potential clinical impact involving decrease in management of radio-resistant and radiosensitive tumor cell lines in cobalt therapy for breast cancer. (author)

  10. Quercetin-induced apoptosis acts through mitochondrial- and caspase-3-dependent pathways in human breast cancer MDA-MB-231 cells.

    Science.gov (United States)

    Chien, Su-Yu; Wu, Yao-Chung; Chung, Jing-Gung; Yang, Jai-Sing; Lu, Hsu-Feng; Tsou, Mei-Fen; Wood, W G; Kuo, Shou-Jen; Chen, Dar-Ren

    2009-08-01

    There has been considerable evidence recently demonstrating the anti-tumour effects of flavonols. Quercetin, an ubiquitous bioactive flavonol, inhibits cells proliferation, induces cell cycle arrest and apoptosis in different cancer cell types. The precise molecular mechanism of quercetin-induced apoptosis in human breast cancer cells is unclear. The purpose of this study was to investigate effects of quercetin on cell viability and to determine its underlying mechanism in human breast cancer MDA-MB-231 cells. Quercetin decreased the percentage of viable cells in a dose- and time-dependent manner, which was associated with cell cycle arrest and apoptosis. Quercetin did not increase reactive oxygen species generation but increased cytosolic Ca(2+) levels and reduced the mitochondrial membrane potential (DeltaPsi(m)). Quercetin treatment promoted activation of caspase-3, -8 and -9 in MDA-MB-231 cells. Caspase inhibitors prevented the quercetin-induced loss of cell viability. Quercetin increased abundance of the pro-apoptotic protein Bax and decreased the levels of anti-apoptotic protein Bcl-2. Confocal laser microscope examination indicated that quercetin promoted apoptosis-inducing factor (AIF) release from mitochondria and stimulated translocation to the nucleus. Taken together, these findings suggest that quercetin results in human breast cancer MDA-MB-231 cell death through mitochondrial- and caspase-3-dependent pathways.

  11. Enhancement of viability of radiosensitive (PBMC and resistant (MDA-MB-231 clones in low-dose-rate cobalt-60 radiation therapy

    Directory of Open Access Journals (Sweden)

    Patrícia Lima Falcão

    2015-06-01

    Full Text Available Abstract Objective: In the present study, the authors investigated the in vitro behavior of radio-resistant breast adenocarcinoma (MDA-MB-231 cells line and radiosensitive peripheral blood mononuclear cells (PBMC, as a function of different radiation doses, dose rates and postirradiation time kinetics, with a view to the interest of clinical radiotherapy. Materials and Methods: The cells were irradiated with Co-60, at 2 and 10 Gy and two different exposure rates, 339.56 cGy.min–1 and the other corresponding to one fourth of the standard dose rates, present over a 10-year period of cobalt therapy. Post-irradiation sampling was performed at pre-established kinetics of 24, 48 and 72 hours. The optical density response in viability assay was evaluated and a morphological analysis was performed. Results: Radiosensitive PBMC showed decrease in viability at 2 Gy, and a more significant decrease at 10 Gy for both dose rates. MDAMB- 231 cells presented viability decrease only at higher dose and dose rate. The results showed MDA-MB-231 clone expansion at low dose rate after 48–72 hours post-radiation. Conclusion: Low dose rate shows a possible potential clinical impact involving decrease in management of radio-resistant and radiosensitive tumor cell lines in cobalt therapy for breast cancer.

  12. The Impact of Soy Isoflavones on MCF-7 and MDA-MB-231 Breast Cancer Cells Using a Global Metabolomic Approach

    Science.gov (United States)

    Uifălean, Alina; Schneider, Stefanie; Gierok, Philipp; Ionescu, Corina; Iuga, Cristina Adela; Lalk, Michael

    2016-01-01

    Despite substantial research, the understanding of the chemopreventive mechanisms of soy isoflavones remains challenging. Promising tools, such as metabolomics, can provide now a deeper insight into their biochemical mechanisms. The purpose of this study was to offer a comprehensive assessment of the metabolic alterations induced by genistein, daidzein and a soy seed extract on estrogen responsive (MCF-7) and estrogen non-responsive breast cancer cells (MDA-MB-231), using a global metabolomic approach. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that all test compounds induced a biphasic effect on MCF-7 cells and only a dose-dependent inhibitory effect on MDA-MB-231 cells. Proton nuclear magnetic resonance (1H-NMR) profiling of extracellular metabolites and gas chromatography-mass spectrometry (GC-MS) profiling of intracellular metabolites confirmed that all test compounds shared similar metabolic mechanisms. Exposing MCF-7 cells to stimulatory concentrations of isoflavones led to increased intracellular levels of 6-phosphogluconate and ribose 5-phosphate, suggesting a possible upregulation of the pentose phosphate pathway. After exposure to inhibitory doses of isoflavones, a significant decrease in glucose uptake was observed, especially for MCF-7 cells. In MDA-MB-231 cells, the glutamine uptake was significantly restricted, leading to alterations in protein biosynthesis. Understanding the metabolomic alterations of isoflavones represents a step forward in considering soy and soy derivates as functional foods in breast cancer chemoprevention. PMID:27589739

  13. The Impact of Soy Isoflavones on MCF-7 and MDA-MB-231 Breast Cancer Cells Using a Global Metabolomic Approach

    Directory of Open Access Journals (Sweden)

    Alina Uifălean

    2016-08-01

    Full Text Available Despite substantial research, the understanding of the chemopreventive mechanisms of soy isoflavones remains challenging. Promising tools, such as metabolomics, can provide now a deeper insight into their biochemical mechanisms. The purpose of this study was to offer a comprehensive assessment of the metabolic alterations induced by genistein, daidzein and a soy seed extract on estrogen responsive (MCF-7 and estrogen non-responsive breast cancer cells (MDA-MB-231, using a global metabolomic approach. The 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay showed that all test compounds induced a biphasic effect on MCF-7 cells and only a dose-dependent inhibitory effect on MDA-MB-231 cells. Proton nuclear magnetic resonance (1H-NMR profiling of extracellular metabolites and gas chromatography-mass spectrometry (GC-MS profiling of intracellular metabolites confirmed that all test compounds shared similar metabolic mechanisms. Exposing MCF-7 cells to stimulatory concentrations of isoflavones led to increased intracellular levels of 6-phosphogluconate and ribose 5-phosphate, suggesting a possible upregulation of the pentose phosphate pathway. After exposure to inhibitory doses of isoflavones, a significant decrease in glucose uptake was observed, especially for MCF-7 cells. In MDA-MB-231 cells, the glutamine uptake was significantly restricted, leading to alterations in protein biosynthesis. Understanding the metabolomic alterations of isoflavones represents a step forward in considering soy and soy derivates as functional foods in breast cancer chemoprevention.

  14. A stable acentric marker chromosome derived from distal 8p: Reactivation of a latent ancient centromere at 8p23.1?

    Energy Technology Data Exchange (ETDEWEB)

    Ohashi, H.; Wakui, K.; Ogawa, K. [Saitama Children`s Medical Ctr., Iwatsuki (Japan)] [and others

    1994-09-01

    Centromere is considered to be an essential chromosomal component for faithful segregation, and acentric chromosomes are unstable and lost through cell divisions. We report a novel marker chromosome that was acentric but stable through cell divisions. The patient was a 2-year-old girl with mental retardation, patent ductus arteriosus and mild dysmorphic features. G-banded chromosome analysis revealed an additional small marker chromosome in all 100 cells examined. Using the targeted chromosome-band painting method, the marker was found to originate from the distal region of 8p, and subsequent two color FISH analysis with cosmid probes around the region revealed the marker was a rearranged chromosome interpreted as 8pter{r_arrow}p23.1{r_arrow}8pter. No centromeric region was involved in the marker. By FISH, no {alpha}-satellite sequence was detected on the marker, while telomere sequence was detected at each end. Antikinetochore immunostaining using a serum from a patient with CREST syndrome showed a pair of signals on the marker, which indicated that a functional kinetochore was present on the marker, presumably at 8p23.1-corresponding region. The patient may provide evidence that an ancient centromere sequence exists at 8p23.1 and was reactivated through the chromosome rearrangement in the patient.

  15. Chamaejasmine Arrests Cell Cycle, Induces Apoptosis and Inhibits Nuclear NF-κB Translocation in the Human Breast Cancer Cell Line MDA-MB-231

    Directory of Open Access Journals (Sweden)

    Yuxian Bai

    2013-01-01

    Full Text Available In this study, the anticancer activity of chamaejasmine was characterized in the human breast cancer cell line, MDA-MB-231. Cell viability and cell cycle distribution were determined by MTT assay and flow cytometry, respectively. Western blotting was performed to determine changes in levels of various proteins. Results showed that treatment with chamaejasmine (4–16 μM inhibited cell proliferation, which correlated with G2/M phase arrest and apoptosis in MDA-MB-231 cells. Chamaejasmine treatment of MDA-MB-231 cells resulted in induction of WAF1/p21 and KIP1/p27, decrease in cyclins A and cyclins B1. Cyclin-dependent kinase (cdk 2 and cdc2 was also decreased after chamaejasmine treatment. Moreover, inhibition of nuclear translocation, phosphorylation of NF-κB, activation of IKKα and IKKβ, inhibition of phosphorylation and degradation of IκBα were also detected in this work. Our findings suggested that chamaejasmine could be explored as a preventive and perhaps as a chemotherapeutic agent in the management of breast cancer.

  16. In vitro response of the human breast cancer cell line MDAMB-231 and human peripheral blood mononuclear cells exposed to {sup 60}Co at single fraction

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, Lidia Maria; Campos, Tarcisio Passos Ribeiro de [Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil). Dept. de Engenharia Nuclear]. E-mail: lidia.andrade@unifenas.br; Leite, M.F. [Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil). Dept. de Fisiologia e Biofisica; Goes, A.M. [Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil). Dept. de Bioquimica e Imunologia

    2005-10-15

    Radiotherapy using gamma rays is a common modality of breast cancer treatment. The aim of this research is to investigate the biological response of the human breast cancer cell line MDAMB-231 and human peripheral blood mononuclear cells (PBMC) exposed in vitro to {sup 60} Co irradiation at a single fraction of 10 Gy, 25 Gy and 50 Gy doses at 136,4 cGy.min{sup -1} rate. Cells were irradiated at room temperature by the Theratron 80 radiotherapy system. Biological response was evaluated through cellular viability using MTT assay and nucleus damages visualized by Propidium Iodide assay and electrophoresis agarose gel after gamma irradiation. Nucleus damages induced by {sup 60} Co irradiation were compared to damage caused by cell exposure to 10% methanol. The 50 Gy dose of irradiation did not stimulate nucleus damages at the same level as that affected by 10% methanol induction in the MDAMB-231. Further studies are necessary to understand these mechanisms in the MDAMB-231 human breast carcinoma cell line.(author)

  17. Antibacterial effect of an extract of the endophytic fungus Alternaria alternata and its cytotoxic activity on MCF-7 and MDA MB-231 tumour cell lines

    Directory of Open Access Journals (Sweden)

    EZHIL ARIVUDAINAMBI U.S.

    2014-06-01

    Full Text Available There is a growing need for new and effective antimicrobial agents to treat life-threatening diseases. Fungal endophytes are receiving increasing attention by natural product chemists due to the diverse and structurally unprecedented compounds, which make them interesting candidates for drug discovery. The present study evaluates the antibacterial activity of ethyl acetate extract of the endophytic fungus Alternaria alternata VN3 on multi-resistant clinical strains of Staphylococcus aureus and Pseudomonas aeruginosa, as well as its cytotoxicity on MCF-7 and MDA MB-231 tumour cell lines of breast cancer. The maximum inhibition zone of 21.4±0.07 mm and 21.5±0.25 mm was observed for S. aureus strain 10 and P. aeruginosa strain 2, respectively. The ethyl acetate extract showed minimal inhibitory concentration ranging from 100 to 900 μg/ml for S. aureus and P. aeruginosa. Further, the ethyl acetate extract of A. alternata VN3 exhibited moderate anticancer activity against MCF-7 and MDA MB-231 cell lines. At 30 μg/ml the cell viability was decreased to 75.5% and 71.8% for MCF-7 and MDA MB-231 cells, respectively. These results clearly indicate that the metabolites of A. alternata VN3 are a potential source for production of new drugs.

  18. In situ morphological assessment of apoptosis induced by Phaleria macrocarpa (Boerl.) fruit ethyl acetate fraction (PMEAF) in MDA-MB-231 cells by microscopy observation.

    Science.gov (United States)

    Kavitha, Nowroji; Chen, Yeng; Kanwar, Jagat R; Sasidharan, Sreenivasan

    2017-03-01

    Phaleria macrocarpa (Boerl.) is a well-known medicinal plant and have been extensively used as traditional medicine for ages in treatment of various diseases. The purpose of this study was to determine the in situ cytotoxicity effect P. macrocarpa fruit ethyl acetate fraction (PMEAF) by using various conventional and modern microscopy techniques. The cytotoxicity of PMEAF treated MDA-MB-231 cells was determined through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay and CyQuant Cell Proliferation Assay after 24h of treatment. Both results were indicated that the PMEAF is a potential anticancer agent with the average IC50 values of 18.10μg/mL by inhibiting the MDA-MB-231 cell proliferation. Various conventional and modern microscopy techniques such as light microscopy, holographic microscopy, transmission (TEM) and scanning (SEM) electron microscope were used for the observation of morphological changes in PMEAF treated MDA-MB-231cells for 24h. The characteristic of apoptotic cell death includes cell shrinkage, membrane blebs, chromatin condensation and the formation of apoptotic bodies were observed. PMEAF might be the best candidate for developing more potent anticancer drugs or chemo-preventive supplements.

  19. Rapid dimerization of quercetin through an oxidative mechanism in the presence of serum albumin decreases its ability to induce cytotoxicity in MDA-MB-231 cells

    Energy Technology Data Exchange (ETDEWEB)

    Pham, Anh; Bortolazzo, Anthony [Department of Biological Sciences, San Jose State University, San Jose, CA 95192-0100 (United States); White, J. Brandon, E-mail: Brandon.White@sjsu.edu [Department of Biological Sciences, San Jose State University, San Jose, CA 95192-0100 (United States)

    2012-10-19

    Highlights: Black-Right-Pointing-Pointer Quercetin cannot be detected intracellularly despite killing MDA-MB-231 cells. Black-Right-Pointing-Pointer Quercetin forms a heterodimer through oxidation in media with serum. Black-Right-Pointing-Pointer The quercetin heterodimer does not kill MDA-MB-231 cells. Black-Right-Pointing-Pointer Ascorbic acid stabilizes quercetin increasing cell death in quercetin treated cells. Black-Right-Pointing-Pointer Quercetin, and not a modified form, is responsible for apoptosis and cell death. -- Abstract: Quercetin is a member of the flavonoid family and has been previously shown to have a variety of anti-cancer activities. We and others have reported anti-proliferation, cell cycle arrest, and induction of apoptosis of cancer cells after treatment with quercetin. Quercetin has also been shown to undergo oxidation. However, it is unclear if quercetin or one of its oxidized forms is responsible for cell death. Here we report that quercetin rapidly oxidized in cell culture media to form a dimer. The quercetin dimer is identical to a dimer that is naturally produced by onions. The quercetin dimer and quercetin-3-O-glucopyranoside are unable to cross the cell membrane and do not kill MDA-MB-231 cells. Finally, supplementing the media with ascorbic acid increases quercetin's ability to induce cell death probably by reduction oxidative dimerization. Our results suggest that an unmodified quercetin is the compound that elicits cell death.

  20. Taiwan cobra cardiotoxin III suppresses EGF/EGFR-mediated epithelial-to-mesenchymal transition and invasion of human breast cancer MDA-MB-231 cells.

    Science.gov (United States)

    Tsai, Pei-Chien; Fu, Yaw-Syan; Chang, Long-Sen; Lin, Shinne-Ren

    2016-03-01

    Breast cancer is a highly malignant carcinoma and most deaths of breast cancer are caused by metastasis. The epithelial-to-mesenchymal transition (EMT) has emerged as a pivotal event in the development of the invasive and metastatic potentials of cancer progression. Epidermal growth factor (EGF) and its receptor, EGFR, play roles in cancer metastasis. CTX III, a basic polypeptide isolated from Naja naja atra venom, has been shown to exhibit anticancer activity; however, the effect of CTX III on the EMT of cancer cells remains elusive. CTX III treatment resulted in morphological changes from elongated and spindle shape to rounded and epithelial-like shape, induced upregulation of E-cadherin and concurrent downregulation of N-cadherin and Vimentin protein levels, corresponding to observed decreases in cell migration and invasion. CTX III treatment also decreased the expression of Snail and Twist in EGF-induced MDA-MB-231 cells. Concurrently, CTX III efficiently inhibited the EGFR phosphorylation and downstream activation of phosphatidylinositol 3-kinase (PI3K)/Akt and ERK1/2. The EGFR specific inhibitor AG1478 significantly suppressed ERK1/2 and Akt phosphorylation, cell migration and invasion, as well as the expressional changes associated with EMT markers in EGF-induced MDA-MB-231 cells. CTX III inhibitory effect on EGF-evoked invasion of MDA-MB-231 cells is mediated through suppressing EGF/EGFR activation and EMT process.

  1. Cardiotoxin III Inhibits Hepatocyte Growth Factor-Induced Epithelial-Mesenchymal Transition and Suppresses Invasion of MDA-MB-231 Cells.

    Science.gov (United States)

    Tsai, Pei-Chien; Fu, Yaw-Syan; Chang, Long-Sen; Lin, Shinne-Ren

    2016-01-01

    The epithelial-mesenchymal transition (EMT) is the first step required for breast cancer to initiate metastasis. In this study, hepatocyte growth factor (HGF) was used as a metastatic inducer of MDA-MB-231 cells. Cardiotoxin III (CTX III) inhibited HGF-induced morphological changes and upregulation of E-cadherin with the concomitant decrease in N-cadherin and Vimentin protein levels, resulting in inhibition of cell migration and invasion. CTX III-induced downregulation of transcription factors, Snail, Twist, and Slug, in MDA-MB-231 cells. CTX III suppressed c-Met phosphorylation and downstream activation of phosphatidylinositol 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK)1/2. The c-Met specific inhibitor PHA665752 attenuated ERK1/2 and Akt phosphorylation, cell migration and invasion, as well as the expressional changes of EMT markers induced by HGF. Taken together, our data suggest that CTX III suppresses HGF/c-Met-induced cell migration and invasion by reversing EMT, which involves the inactivation of the HGF/c-Met-mediated ERK1/2 and PI3K/Akt pathways in MDA-MB-231 cells.

  2. Pyruvate Carboxylase Is Up-Regulated in Breast Cancer and Essential to Support Growth and Invasion of MDA-MB-231 Cells.

    Science.gov (United States)

    Phannasil, Phatchariya; Thuwajit, Chanitra; Warnnissorn, Malee; Wallace, John C; MacDonald, Michael J; Jitrapakdee, Sarawut

    2015-01-01

    Pyruvate carboxylase (PC) is an anaplerotic enzyme that catalyzes the carboxylation of pyruvate to oxaloacetate, which is crucial for replenishing tricarboxylic acid cycle intermediates when they are used for biosynthetic purposes. We examined the expression of PC by immunohistochemistry of paraffin-embedded breast tissue sections of 57 breast cancer patients with different stages of cancer progression. PC was expressed in the cancerous areas of breast tissue at higher levels than in the non-cancerous areas. We also found statistical association between the levels of PC expression and tumor size and tumor stage (P MB-435 (moderate metastasis) and MDA-MB-231 (high metastasis). The abundance of both PC mRNA and protein in MDA-MB-231 and MDA-MB-435 cells was 2-3-fold higher than that in MCF-7 and SKBR3 cells. siRNA-mediated knockdown of PC expression in MDA-MB-231 and MDA-MB-435 cells resulted in a 50% reduction of cell proliferation, migration and in vitro invasion ability, under both glutamine-dependent and glutamine-depleted conditions. Overexpression of PC in MCF-7 cells resulted in a 2-fold increase in their proliferation rate, migration and invasion abilities. Taken together the above results suggest that anaplerosis via PC is important for breast cancer cells to support their growth and motility.

  3. Production of actinium-225 for alpha particle mediated radioimmunotherapy.

    Science.gov (United States)

    Boll, Rose A; Malkemus, Dairin; Mirzadeh, Saed

    2005-05-01

    The initial clinical trials for treatment of acute myeloid leukemia have demonstrated the effectiveness of the alpha emitter (213)Bi in killing cancer cells. Bismuth-213 is obtained from a radionuclide generator system from decay of 10-days (225)Ac parent. Recent pre-clinical studies have also shown the potential application of both (213)Bi, and the (225)Ac parent radionuclide in a variety of cancer systems and targeted radiotherapy. This paper describes our five years of experience in production of (225)Ac in partial support of the on-going clinical trials. A four-step chemical process, consisting of both anion and cation exchange chromatography, is utilized for routine separation of carrier-free (225)Ac from a mixture of (228)Th, (229)Th and (232)Th. The separation of Ra and Ac from Th is achieved using the marcoporous anion exchange resin MP1 in 8M HNO(3) media. Two sequential MP1/NO(3) columns provide a separation factor of approximately 10(6) for Ra and Ac from Th. The separation of Ac from Ra is accomplished on a low cross-linking cation exchange resin AG50-X4 using 1.2M HNO(3) as eluant. Two sequential AG50/NO(3) columns provide a separation factor of approximately 10(2) for Ac from Ra. A 60-day processing schedule has been adopted in order to reduce the processing cost and to provide the highest levels of (225)Ac possible. Over an 8-week campaign, a total of approximately 100 mCi of (225)Ac (approximately 80% of the theoretical yield) is shipped in 5-6 batches, with the first batch typically consisting of approximately 50 mCi. After the initial separation and purification of Ac, the Ra pool is re-processed on a bi-weekly schedule or as needed to provide smaller batches of (225)Ac. The averaged radioisotopic purity of the (225)Ac was 99.6 +/- 0.7% with a (225)Ra content of < or =0.6%, and an average (229)Th content of (4(-4)(+5)) x 10(-5)%.

  4. Isolation of Actinium from Neutron-irradiated Thorium-I

    Institute of Scientific and Technical Information of China (English)

    1994-01-01

    Isolation of Actinium from Neutron-irradiated Thorium-I¥YangWeifan;YuanShuanggui;MuWantong;ZhangXueqian;LiZhongweiandZhaoLili...

  5. 乳腺癌MDA-MB-231细胞源exosomes对血管内皮细胞EGFR表达的影响%Effect of exosomes derived from breast cancer cell line MDA-MB-231 on EGFR expression in HUVECs

    Institute of Scientific and Technical Information of China (English)

    谢莹珊; 沈宜; 隆霜; 范维柯; 姜蓉; 陈黎

    2012-01-01

    目的 研究人乳腺癌MDA-MB-231细胞源exosomes介导表皮生长因子受体(EGFR)对人脐静脉内皮细胞株(HUVECs) EGFR表达影响,探讨肿瘤组织血管内皮细胞异常表达EGFR的机制.方法 超速离心及密度梯度离心法提取MDA-MB-231细胞源exosomes;免疫细胞化学法检测MDA-MB-231细胞EGFR的表达;Western blot法检测MDA-MB-231细胞、exosomes及HUVECs EGFR蛋白表达;免疫细胞化学法检测HUVECs与exosomes共培养24 h后EGFR的表达;RT-PCR法检测MDA-MB-231细胞与实验组HUVECs细胞 EGFR mRNA的表达.结果 EGFR在MDA-MB-231细胞中呈高表达,MDA-MB-231细胞及exosomes可见相对分子质量为170×103的EGFR蛋白呈阳性反应带,HUVECs呈阴性反应带;HUVECs与exosomes共培养24 h后,镜下可见实验组部分HUVECs细胞质有淡黄色或棕黄色颗粒,EGFR阳性表达率为(21.4±3.1)%,与对照组(无EGFR蛋白表达)比较,差异有统计学意义(P<0.01).MDA-MB-231细胞EGFR mRNA表达阳性,而实验组HUVECs EGFR mRNA表达阴性.结论 MDA-MB-231细胞源exosomes携带癌基因EGFR,并能介导其向周围血管内皮细胞转移,这可能是肿瘤内皮细胞异常表达EGFR的一种方式.%Objective To study the effect of exosomes derived from breast cancer cell line MDA-MB-231 on epidermal growth factor receptor(EGFR) expression in human umbilical vein endothelial cells(HUVKCs) and to research the possible manner of abnormal expression EGFR of tumor endothelial cell. Methods Exosomes were purified by serial ultracentrifugation and sugar density ultracentrifugation. The expression of KGFR in MDA-MB-231 was detected by immunocytochemistry and Western blotting. The expression of EGFR in exosomes and HUVECs was detected by Western blotting. The expression of EGFR in HUVECs with exosomes co-cultured 24 h was detected by immunocytochemistry. RT-PCR was used to detect the mRNA expression of EGFR in MDA-MB-231 and experimental group. Results MDA-MB-231 cells expressed high level of EGFR. In

  6. Hyperglycemia regulates thioredoxin-ROS activity through induction of thioredoxin-interacting protein (TXNIP in metastatic breast cancer-derived cells MDA-MB-231

    Directory of Open Access Journals (Sweden)

    Friday Ellen

    2007-06-01

    Full Text Available Abstract Background We studied the RNA expression of the genes in response to glucose from 5 mM (condition of normoglycemia to 20 mM (condition of hyperglycemia/diabetes by microarray analysis in breast cancer derived cell line MDA-MB-231. We identified the thioredoxin-interacting protein (TXNIP, whose RNA level increased as a gene product particularly sensitive to the variation of the level of glucose in culture media. We investigated the kinesis of the TXNIP RNA and protein in response to glucose and the relationship between this protein and the related thioredoxin (TRX in regulating the level of reactive oxygen species (ROS in MDA-MB-231 cells. Methods MDA-MB-231 cells were grown either in 5 or 20 mM glucose chronically prior to plating. For glucose shift (5/20, cells were plated in 5 mM glucose and shifted to 20 mM at time 0. Cells were analyzed with Affymetrix Human U133A microarray chip and gene expression profile was obtained. Semi-quantitative RT-PCR and Western blot was used to validate the expression of TXNIP RNA and protein in response to glucose, respectively. ROS were detected by CM-H2DCFDA (5–6-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate and measured for mean fluorescence intensity with flow cytometry. TRX activity was assayed by the insulin disulfide reducing assay. Results We found that the regulation of TXNIP gene expression by glucose in MDA-MB-231 cells occurs rapidly within 6 h of its increased level (20 mM glucose and persists through the duration of the conditions of hyperglycemia. The increased level of TXNIP RNA is followed by increased level of protein that is associated with increasing levels of ROS and reduced TRX activity. The inhibition of the glucose transporter GLUT1 by phloretin notably reduces TXNIP RNA level and the inhibition of the p38 MAP kinase activity by SB203580 reverses the effects of TXNIP on ROS-TRX activity. Conclusion In this study we show that TXNIP is an oxidative stress responsive

  7. Biodegradable Eri silk nanoparticles as a delivery vehicle for bovine lactoferrin against MDA-MB-231 and MCF-7 breast cancer cells

    Directory of Open Access Journals (Sweden)

    Roy K

    2015-12-01

    Full Text Available Kislay Roy,1,* Yogesh S Patel,1,* Rupinder K Kanwar,1 Rangam Rajkhowa,2 Xungai Wang,2 Jagat R Kanwar1 1Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research (NLIMBR, Centre for Molecular and Medical Research (C-MMR, School of Medicine (SoM, Faculty of Health, 2Institute for Frontier Materials (IFM, Deakin University, Waurn Ponds, VIC, Australia *These authors contributed equally to this work Abstract: This study used the Eri silk nanoparticles (NPs for delivering apo-bovine lactoferrin (Apo-bLf (~2% iron saturated and Fe-bLf (100% iron saturated in MDA-MB-231 and MCF-7 breast cancer cell lines. Apo-bLf and Fe-bLf-loaded Eri silk NPs with sizes between 200 and 300 nm (±10 nm showed a significant internalization within 4 hours in MDA-MB-231 cells when compared to MCF-7 cells. The ex vivo loop assay with chitosan-coated Fe-bLf-loaded silk NPs was able to substantiate its future use in oral administration and showed the maximum absorption within 24 hours by ileum. Both Apo-bLf and Fe-bLf induced increase in expression of low-density lipoprotein receptor-related protein 1 and lactoferrin receptor in epidermal growth factor (EGFR-positive MDA-MB-231 cells, while transferrin receptor (TfR and TfR2 in MCF-7 cells facilitated the receptor-mediated endocytosis of NPs. Controlled and sustained release of both bLf from silk NPs was shown to induce more cancer-specific cytotoxicity in MDA-MB-231 and MCF-7 cells compared to normal MCF-10A cells. Due to higher degree of internalization, the extent of cytotoxicity and apoptosis was significantly higher in MDA-MB-231 (EGFR+ cells when compared to MCF-7 (EGFR- cells. The expression of a prominent anti-cancer target, survivin, was found to be downregulated at both gene and protein levels. Taken together, all the observations suggest the potential use of Eri silk NPs as a delivery vehicle for an anti-cancer milk protein, and indicate bLf for the treatment of breast cancer. Keywords: breast

  8. [Effect of autophagy inhibitor combined with EGFR inhibitor on triple-negative breast cancer MDA-MB-468 and MDA-MB-231 cells].

    Science.gov (United States)

    Liu, Z Y; He, K W; Song, X G; Wang, X Z; Zhuo, P Y; Wang, X W; Ma, Q H; Huo, Z J; Yu, Z Y

    2016-06-23

    To investigate the effect of combined administration of autophagy inhibitor 3-methyladenine/bafilomycin A1 and EGFR inhibitor gefitinib on triple-negative breast cancer MDA-MB-468, MDA-MB-231 cells and estrogen receptor-positive MCF-7 cells. All the cells were treated with 3-methyladenine/bafilomycin A1 and/or gefitinib. The effect of autophagy inhibitor and gefitinib on the cell growth was evaluated by MTT assay. Cell apoptosis was detected by flow cytometry. Western blot analysis was used to determine the alteration of autophagy-related protein (such as LC3) and apoptosis-related proteins (such as caspase-3 and caspase-9). MTT assay showed that the IC50 in the GE+ 3-MA and GE+ BAF groups were (4.1±0.2) μmol/L and (3.8±0.3) μmol/L, significantly lower than that of the gefitinib alone group [(7.0±0.2) μmol/L] in MDA-MB-468 cells (PMB231 cells (PMB-468 cells in GE, GE+ 3-MA and GE+ BAF groups were (12.43±3.18)%, (23.37±2.71)% and (18.71±2.81)%, respectively. The apoptosis rates of MDA-MB-231 cells of the GE, GE+ 3-MA and GE+ BAF groups were (12.15±1.82)%, (16.94±2.19)% and (33.83±5.92) %, significantly higher than that of the gefitinib alone group (All P0.05). Western blot data showed that the expression levels of LC3 and p-Akt were decreased in the combined groups than that of the gefitinib alone group, while the p-PTEN, caspase-3 and caspase-9 were increased. Autophagy inhibitor may enhance the sensitivity to gefitinib in MDA-MB-468 and MDA-MB-231 cells by activation of the PTEN/P13K/Akt pathway. Apoptosis in MDA-MB-468 and MDA-MB-231 cells might be enhanced by the combination treatment through caspase cascade.

  9. EGFR signaling pathways are wired differently in normal 184A1L5 human mammary epithelial and MDA-MB-231 breast cancer cells.

    Science.gov (United States)

    Speth, Zachary; Islam, Tanzila; Banerjee, Kasturi; Resat, Haluk

    2017-03-29

    Because of differences in the downstream signaling patterns of its pathways, the role of the human epidermal growth factor family of receptors (HER) in promoting cell growth and survival is cell line and context dependent. Using two model cell lines, we have studied how the regulatory interaction network among the key proteins of HER signaling pathways may be rewired upon normal to cancerous transformation. We in particular investigated how the transcription factor STAT3 and several key kinases' involvement in cancer-related signaling processes differ between normal 184A1L5 human mammary epithelial (HME) and MDA-MB-231 breast cancer epithelial cells. Comparison of the responses in these cells showed that normal-to-cancerous cellular transformation causes a major re-wiring of the growth factor initiated signaling. In particular, we found that: i) regulatory interactions between Erk, p38, JNK and STAT3 are triangulated and tightly coupled in 184A1L5 HME cells, and ii) STAT3 is only weakly associated with the Erk-p38-JNK pathway in MDA-MB-231 cells. Utilizing the concept of pathway substitution, we predicted how the observed differences in the regulatory interactions may affect the proliferation/survival and motility responses of the 184A1L5 and MDA-MB-231 cells when exposed to various inhibitors. We then validated our predictions experimentally to complete the experiment-computation-experiment iteration loop. Validated differences in the regulatory interactions of the 184A1L5 and MDA-MB-231 cells indicated that instead of inhibiting STAT3, which has severe toxic side effects, simultaneous inhibition of JNK together with Erk or p38 could be a more effective strategy to impose cell death selectively to MDA-MB-231 cancer cells while considerably lowering the side effects to normal epithelial cells. Presented analysis establishes a framework with examples that would enable cell signaling researchers to identify the signaling network structures which can be used to

  10. Mentha arvensis (Linn.)-mediated green silver nanoparticles trigger caspase 9-dependent cell death in MCF7 and MDA-MB-231 cells.

    Science.gov (United States)

    Banerjee, Prajna Paramita; Bandyopadhyay, Arindam; Harsha, Singapura Nagesh; Policegoudra, Rudragoud S; Bhattacharya, Shelley; Karak, Niranjan; Chattopadhyay, Ansuman

    2017-01-01

    Leaf extract of Mentha arvensis or mint plant was used as reducing agent for the synthesis of green silver nanoparticles (GSNPs) as a cost-effective, eco-friendly process compared to that of chemical synthesis. The existence of nanoparticles was characterized by ultraviolet-visible spectrophotometry, dynamic light scattering, Fourier transform infrared spectroscopy, X-ray diffraction, energy-dispersive X-ray analysis, atomic-force microscopy and transmission electron microscopy analyses, which ascertained the formation of spherical GSNPs with a size range of 3-9 nm. Anticancer activities against breast cancer cell lines (MCF7 and MDA-MB-231) were studied and compared with those of chemically synthesized (sodium borohydride [NaBH4]-mediated) silver nanoparticles (CSNPs). Cell survival of nanoparticle-treated and untreated cells was studied by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Cell-cycle analyses were carried out using fluorescence-activated cell sorting. Cell morphology was observed by fluorescence microscopy. Expression patterns of PARP1, P53, P21, Bcl2, Bax and cleaved caspase 9 as well as caspase 3 proteins in treated and untreated MCF7 and MDA-MB-231 cells were studied by Western blot method. MTT assay results showed that Mentha arvensis-mediated GSNPs exhibited significant cytotoxicity toward breast cancer cells (MCF7 and MDA-MB-231), which were at par with that of CSNPs. Cell cycle analyses of MCF7 cells revealed a significant increase in sub-G1 cell population, indicating cytotoxicity of GSNPs. On the other hand, human peripheral blood lymphocytes showed significantly less cytotoxicity compared with MCF7 and MDA-MB-231 cells when treated with the same dose. Expression patterns of proteins suggested that GSNPs triggered caspase 9-dependent cell death in both cell lines. The Ames test showed that GSNPs were nonmutagenic in nature. GSNPs synthesized using Mentha arvensis may be considered as a promising anticancer agent in

  11. Effects of down-regulatedβ-catenin on epithelial mesenchymal transition, invasion and migration ability of breast cancer cell line MDA-MB-231%β-catenin下调对乳腺癌MDA-MB-231细胞上皮间质转化及侵袭迁移能力的影响

    Institute of Scientific and Technical Information of China (English)

    许光伟; 曹旭晨

    2015-01-01

    Objective To investigate the effect ofβ-catenin on epithelial mesenchymal phenotype and invasion migra⁃tion ability of breast cancer cell line MDA-MB-231. Methods Small interfering RNA (siRNA) targetingβ-catenin plas⁃mid was transfected into MDA-MB-231 cell line. Immunofluorescence staining was used to observe the expression of β-catenin. The expressions of epithelial cell marker E-cadherin and mesenchymal marker vimentin, epithelial mesenchymal transition correlation factor Twist1 and Snail were detected by Western blot assay. Invasion and migration ability was com⁃pared by transwell invasion and wound healing assay between control group, the MDA-MB-231 group andβ-catenin down-regulated group. Results Immunofluorescence staining showed thatβ-catenin was expressed in cell membrane, cytoplasm or nucleus in MDA-MB-231 group and control group. There was a decreased expression in β-catenin down-regulated group, and no expression in cytoplasm or nucleus. The expression of E-cadherin was increased, while vimentin, Twist 1 and Snail expression decreased inβ-catenin down-regulated cells. Transwell invasion and wound healing assay results proved that transmembrane cell number and migration distance were significantly lower in β-catenin down-regulated group than those of MDA-MB-231 group and control group (P<0.05). Conclusion The down-regulation ofβ-catenin inhibits Wnt/β-catenin activation that decreases the mesenchymal phenotype but increases epithelial phenotype of breast cancer cells MDA-MB-231, and which reduces the cell invasion and migration ability in vitro.%目的:探讨β-连环蛋白(β-catenin)对乳腺癌细胞系MDA-MB-231细胞上皮间质表型和侵袭迁移能力的影响。方法用β-catenin siRNA质粒转染乳腺癌MDA-MB-231细胞(对照组),免疫荧光染色观察β-catenin的表达情况。Western blot检测上皮标记蛋白E-cadherin、间质标记蛋白vimentin及上皮间质转化相关调控因子Twist1和Snail的

  12. 231例基层社区女性压力性尿失禁早期干预效果观察%Investigation on efficiency of 231 female cases by early intervention on stressed-urinary incontinence

    Institute of Scientific and Technical Information of China (English)

    吴永红; 胡铧文; 韩春艳

    2015-01-01

    Objective To observe the effect of early intervention of women suffering from stress urinary incontinence in their menopausal transition, provide the best prevention measure, and reduce the incidence of stress urinary incontinence.Methods An investigation of 1300 cases of women, aged from 40~55, from the three streets in Nanshan District in Shenzhen.They were screened for stress urinary incontinence by filling the self-administered questionnaires.231 women (206 mild cases, 25 moderate cases) suffered from stress urinary incontinence.They were randomly divided into three groups according to their degrees of illness.A group had 77 cases who used the topical estrogen cream.B group had 77 cases who used the rehabilitation methods including pelvic floor muscle exercises.C group had 77 cases who used the pelvic floor muscle exercises with combination of topical estrogen cream.All cases were analyzed after 1 and 3 months based on the indicators.Results The efficiency rate after 1 month for A, B, and C group was 41.59%, 62.34%, and 75.33% respectively.It increased to 68.83%, 83.12%, and 94.81% respectively.There was a significant difference (P <0.05). Conclusions 1.Host community health education seminars regularly to improve female's knowledge on the illness and their compliance.2.Female should start the pelvic floor muscle earlier to avoid the occurrence of stress urinary incontinence.3.Increase physical activity;enhance self-care awareness;improve the quality of life of the menopausal transition female.4.For female, who suffered from mild to moderate stress urinary incontinence, should use the pelvic floor muscle rehabilitation with combination of topical estrogen cream treatments.%目的:探索基层社区绝经过渡期患压力性尿失禁女性早期干预的效果观察,提供最佳的防治措施,降低压力性尿失禁的发生。方法南山区三个街道的基层社区女性年龄在40~55岁之间共1300例,采用自填问卷方式进行压力性

  13. Calcium binding promotes prion protein fragment 90-231 conformational change toward a membrane destabilizing and cytotoxic structure.

    Directory of Open Access Journals (Sweden)

    Sacha Sorrentino

    Full Text Available The pathological form of prion protein (PrP(Sc, as other amyloidogenic proteins, causes a marked increase of membrane permeability. PrP(Sc extracted from infected Syrian hamster brains induces a considerable change in membrane ionic conductance, although the contribution of this interaction to the molecular mechanism of neurodegeneration process is still controversial. We previously showed that the human PrP fragment 90-231 (hPrP₉₀₋₂₃₁ increases ionic conductance across artificial lipid bilayer, in a calcium-dependent manner, producing an alteration similar to that observed for PrP(Sc. In the present study we demonstrate that hPrP₉₀₋₂₃₁, pre-incubated with 10 mM Ca⁺⁺ and then re-suspended in physiological external solution increases not only membrane conductance but neurotoxicity as well. Furthermore we show the existence of a direct link between these two effects as demonstrated by a highly statistically significant correlation in several experimental conditions. A similar correlation between increased membrane conductance and cell degeneration has been observed assaying hPrP₉₀₋₂₃₁ bearing pathogenic mutations (D202N and E200K. We also report that Ca⁺⁺ binding to hPrP₉₀₋₂₃₁ induces a conformational change based on an alteration of secondary structure characterized by loss of alpha-helix content causing hydrophobic amino acid exposure and proteinase K resistance. These features, either acquired after controlled thermal denaturation or induced by D202N and E200K mutations were previously identified as responsible for hPrP₉₀₋₂₃₁ cytotoxicity. Finally, by in silico structural analysis, we propose that Ca⁺⁺ binding to hPrP₉₀₋₂₃₁ modifies amino acid orientation, in the same way induced by E200K mutation, thus suggesting a pathway for the structural alterations responsible of PrP neurotoxicity.

  14. Calcium binding promotes prion protein fragment 90-231 conformational change toward a membrane destabilizing and cytotoxic structure.

    Science.gov (United States)

    Sorrentino, Sacha; Bucciarelli, Tonino; Corsaro, Alessandro; Tosatto, Alessio; Thellung, Stefano; Villa, Valentina; Schininà, M Eugenia; Maras, Bruno; Galeno, Roberta; Scotti, Luca; Creati, Francesco; Marrone, Alessandro; Re, Nazzareno; Aceto, Antonio; Florio, Tullio; Mazzanti, Michele

    2012-01-01

    The pathological form of prion protein (PrP(Sc)), as other amyloidogenic proteins, causes a marked increase of membrane permeability. PrP(Sc) extracted from infected Syrian hamster brains induces a considerable change in membrane ionic conductance, although the contribution of this interaction to the molecular mechanism of neurodegeneration process is still controversial. We previously showed that the human PrP fragment 90-231 (hPrP₉₀₋₂₃₁) increases ionic conductance across artificial lipid bilayer, in a calcium-dependent manner, producing an alteration similar to that observed for PrP(Sc). In the present study we demonstrate that hPrP₉₀₋₂₃₁, pre-incubated with 10 mM Ca⁺⁺ and then re-suspended in physiological external solution increases not only membrane conductance but neurotoxicity as well. Furthermore we show the existence of a direct link between these two effects as demonstrated by a highly statistically significant correlation in several experimental conditions. A similar correlation between increased membrane conductance and cell degeneration has been observed assaying hPrP₉₀₋₂₃₁ bearing pathogenic mutations (D202N and E200K). We also report that Ca⁺⁺ binding to hPrP₉₀₋₂₃₁ induces a conformational change based on an alteration of secondary structure characterized by loss of alpha-helix content causing hydrophobic amino acid exposure and proteinase K resistance. These features, either acquired after controlled thermal denaturation or induced by D202N and E200K mutations were previously identified as responsible for hPrP₉₀₋₂₃₁ cytotoxicity. Finally, by in silico structural analysis, we propose that Ca⁺⁺ binding to hPrP₉₀₋₂₃₁ modifies amino acid orientation, in the same way induced by E200K mutation, thus suggesting a pathway for the structural alterations responsible of PrP neurotoxicity.

  15. 雌激素受体β1对乳腺癌MDA-MB-231细胞上皮间质转化影响的初步研究%Primary study on estrogen receptor β1 impeding epithelial-mesenchymal transition of breast cancer MDA-MB-231 cells

    Institute of Scientific and Technical Information of China (English)

    周艳; 陈莉; 明佳; 唐鹏; 张毅; 杨新华; 姜军

    2012-01-01

    目的 将雌激素受体ERβ1真核表达质粒转染到人乳腺癌MDA-MB-231细胞中,观察外源性ERβ1基因转染MDA-MB-231细胞后对E-cadherin、Vimentin等基因表达和细胞上皮间质转化的影响,探讨ERβ1在乳腺癌发生发展中的生物学作用机制.方法 应用脂质体法将ERβ1真核表达质粒转染至乳腺癌MDA-MB-231细胞中,分别用实时荧光定量PCR、Western Blot检测转染前后细胞中ERβ1、E-cadherin、Vimentin mRNA和蛋白表达的变化;并用细胞增殖曲线显示转染后细胞增殖能力的改变.所有数据以±s表示,多个样本均数间的比较用单因素方差分析,组间比较采用SNK法.细胞生长曲线变化采用重复测量方差分析.结果 外源性ERβ1真核表达质粒转染组MDA-MB-231细胞较未转染组ERβ1、E-cadherin mRNA和蛋白水平明显增强(P<0.010),Vimentin mRNA水平明显减少(P<0.010),细胞增殖能力明显减弱.结论 ERβ1可能参与抑制乳腺癌MDA-MB-231细胞的上皮间质转化过程.%Objective To explore the effect of exogenous ERβ1 gene on the expression of E-cadherin and vimentin by transfecting recombinant eukaryotic expressing vector containing ERβ1 cDNA into human breast cancer MDA-MB-231 cells, and to investigate the biological role of ERβ1 in epithelial-mesenchymal transition of breast cancer cells. Methods Recombinant eukaryotic expressing vector containing ER β1 cDNA was transfected into human breast cancer MDA -MB-231 cells. The mRNA and protein expression levels of ERβ1, E-eadherin and vimentin were tested by real-time polymerase chain reaction and Western blot, respectively. The cell growth curve showed the change of proliferation ability in MDA-MB-231. All data were expressed as x±s. Single factor analysis of variance was used to compare the multiple sample means , and SNK method for group comparison. Changes in the cell growth curve were analyzed using repeated ANOVA . Results The mRNA and protein expression levels of ERβ1

  16. Oridonin induces MDA-MB-231 cells apoptosis through PI3K/Akt pathway in vitro%冬凌草甲素通过PI3K/Akt通路诱导MDA-MB-231细胞的凋亡

    Institute of Scientific and Technical Information of China (English)

    汪茗; 章尧; 谢向荣; 戚之琳; 毕富勇

    2013-01-01

    AIM: To research the proliferation inhibitory effect of oridonin on human breast cancer MDA-MB-231 cells and explore the mech anism of the inhibitory effect.METHODS: MDA-MB-231 cells were incubated with oridonin in vitro.Morphological changes of MDA-MB-231 cells induced by oridonin for 24 h were ob served by invert microscrope.The cell viability rate was evaluated by MTT assay.The cell ap-optotic rate was evalutated by flow cytometry (FCM).The apoptosis associated protein level of procaspase-3, PARP,Akt, p-Akt, p-GSK 3β was examined by Western blotting.RESULTS: The apoptosis phenomenon of MDA-MB-231 cells induced by oridonin for 24 h could be ob served.The apoptosis phenomenon of 24 μmol/ L group was more obvious than other groups.The cell viability rate induced by 6,12,24 μmol/ L oridonin was decreased and apoptotic rate was increased in a time- and dose-dependent manner (P<0.01).Oridonin cleaved PARP which is the substrate of caspase-3 in a dose-dependent manner(P<0.05).Oridonin also down- regula ted the protein level of procaspase-3, phospho-Akt(p-Akt) and phospho-GSK3β (p- GSK3β) in a dose-dependent manner(P<0.05).CONCLU SION: Oridonin can inhibit the proliferation of human breast cancer MDA-MB-231 cells and in duce cell apoptosis by inhibiting PI3K/Akt path way.%目的:研究冬凌草甲素对人乳腺癌MDA-MB-231细胞增殖产生的影响,初步探讨其作用机理.方法:体外培养人乳腺癌MDA-MB-231细胞,采用6、12、24 μmol/L冬凌草甲素对其进行处理,采用倒置显微镜进行细胞形态学观察,MTT比色法检测细胞存活率,流式细胞术检测细胞凋亡率,Western blotting检测凋亡相关蛋白procaspase-3、PARP及Akt、p-Akt、p-GSK3β表达的变化.结果:冬凌草甲素作用MDA-MB-231细胞24 h后,可观察到细胞凋亡的形态学改变,以24 μmol/L组最为明显.实验组与对照组相比,细胞存活率显著降低、凋亡率显著升高(P<0.01),具有时间和剂量

  17. PIB5PA增强三阴性乳腺癌MDA-MB-231细胞对紫杉醇的敏感性的研究%PIB5PA enhance the Sensitivity of Triple-negative Breast CancerCell line MDA-MB-231 to Paclitaxel through Up-regulation of Bim

    Institute of Scientific and Technical Information of China (English)

    张楠楠; 胡春松; 陈振东

    2016-01-01

    目的 探讨PIB5PA(phosphatidylinositol 4,5-bisphosphate5-phosphatase)基因转染人三阴性乳腺癌MDA-MB-231细胞后对紫杉醇敏感性的影响.方法 体外培养人乳腺癌MCF-7和MDA-MB-231细胞株,MTT法观察不同浓度(0,0.1,0.2,0.3,0.4,0.5μmol/L)紫杉醇处理后对两株细胞生存率的影响;流式细胞PI单染法检测两株细胞凋亡率的差异;蛋白免疫印迹法检测0.3 μmol/L紫杉醇处理两株细胞不同时间点Bcl-2家族成员蛋白表达差异.将pCGN-PIB5 PA质粒转染对紫杉醇相对不敏感MDA-MB-231细胞,0.3μmol/L紫杉醇处理24h,免疫蛋白印迹法检测PIB5PA,磷酸化Akt以及Bcl-2家族成员蛋白的表达,MTT和PI单染法检测MDA-MB-231细胞对紫杉醇敏感性的改变.结果 MDA-MB-231细胞对紫杉醇敏感性较差,过表达PIB5 PA后细胞生存率明显降低,细胞中磷酸化Akt水平降低,Bim(Bcl-2 interacting mediator of cell death)表达明显增高,对紫杉醇敏感性明显增强.结论 PIB5PA可能通过上调Bim表达增强三阴性乳腺癌MDA-MB-231细胞对紫杉醇的敏感性.

  18. Culture supernatants of breast cancer cell line MDA-MB-231 treated with parthenolide inhibit the proliferation, migration, and lumen formation capacity of human umbilical vein endothelial cells

    Institute of Scientific and Technical Information of China (English)

    LI Cai-juan; GUO Su-fen; SHI Tie-mei

    2012-01-01

    Background Parthenolide has been tested for anti-tumor activities,such as anti-proliferation and pro-apoptosis in recent studies.However,little is known about its role in the process of tumor angiogenesis.This study aims to investigate the effects and potential mechanisms of parthenolide on the proliferation,migration and lumen formation capacity of human umbilical vein endothelial cells.Methods Different concentrations of parthenolide were applied to the human breast cancer cell line MDA-MB-231 cells.After 24-hour incubation,the culture supematants were harvested and used to treat human umbilical vein endothelial cells for 24 hours.Then an inverted fluorescence phase contrast microscope was used to evaluate the human umbilical vein endothelial cells.The secretion of vascular endothelial growth factor (VEGF),interleukin (IL)-8 and matrix metalloproteinases (MMP)-9 in the culture supernatant of the MDA-MB-231 cells was then measured with enzyme-linked immunosorbent assay (ELISA) assays.Results Suppression of proliferation,migration,and the lumen formation capacity of human umbilical vein endothelial cells was observed in the presence of the culture supernatants from the breast cancer cell line treated with different concentrations of parthenolide.Parthenolide decreased the levels of the angiogenic factors MMP-9,VEGF,and IL-8secreted by the MDA-MB-231 cells.Conclusions Parthenolide may suppress angiogenesis through decreasing angiogenic factors secreted by breast cancer cells to interfere with the proliferation,migration and lumen-like structure formation of endothelial cells,thereby inhibiting tumor growth.It is a promising potential anti-angiogenic drug.

  19. X-231A demonstration of in-situ remediation of DNAPL compounds in low permeability media by soil fracturing with thermally enhanced mass recovery or reactive barrier destruction

    Energy Technology Data Exchange (ETDEWEB)

    Siegrist, R.L. [Oak Ridge National Lab., TN (United States)]|[Colorado School of Mines, Golden, CO (United States). Environmental Science and Engineering Div.; Lowe, K.S. [Oak Ridge National Lab., Grand Junction, CO (United States). Life Sciences Div.; Murdoch, L.D. [FRx, Inc., Cincinnati, OH (United States)]|[Clemson Univ., SC (United States); Slack, W.W. [FRx, Inc., Cincinnati, OH (United States); Houk, T.C. [Lockheed Martin Energy Systems, Piketon, OH (United States)

    1998-03-01

    The overall goal of the program of activities is to demonstrate robust and cost-effective technologies for in situ remediation of DNAPL compounds in low permeability media (LPM), including adaptations and enhancements of conventional technologies to achieve improved performance for DNAPLs in LPM. The technologies sought should be potential for application at simple, small sites (e.g., gasoline underground storage tanks) as well as at complex, larger sites (e.g., DOE land treatment units). The technologies involved in the X-231A demonstration at Portsmouth Gaseous Diffusion Plant (PORTS) utilized subsurface manipulation of the LPM through soil fracturing with thermally enhanced mass recovery or horizontal barrier in place destruction. To enable field evaluation of these approaches, a set of four test cells was established at the X-231A land treatment unit at the DOE PORTS plant in August 1996 and a series of demonstration field activities occurred through December 1997. The principal objectives of the PORTS X-231A demonstration were to: determine and compare the operational features of hydraulic fractures as an enabling technology for steam and hot air enhanced soil vapor extraction and mass recovery, in situ interception and reductive destruction by zero valent iron, and in situ interception and oxidative destruction by potassium permanganate; determine the interaction of the delivered agents with the LPM matrix adjacent to the fracture and within the fractured zone and assess the beneficial modifications to the transport and/or reaction properties of the LPM deposit; and determine the remediation efficiency achieved by each of the technology strategies.

  20. EGFR antisense RNA blocks expression of the epidermal growth factor receptor and partially reverse the malignant phenotype of human breast cancer MDA—MB—231 cells

    Institute of Scientific and Technical Information of China (English)

    FANWENHONG; YINGLINLU; 等

    1998-01-01

    The effects of human EGFR to the malignant phenotype of human breast cancer cell line MDA-MB-231 were investigated experimentally.A retroviral vector containing a 5'1350bp fragment of the human EGFR cDNA in the antisense orientation was transfected into targeted cells by lipofectamine.The effects on cell proliferation,cell cycle and adherent ability to extracellular matrix(ECM) components were studied after the expression of antisense transcripts to EGFR5'1350bp fragment in target cells,In vitro studies showed that the growth ability of the transfected cells was partialy inhibited in comparison to parental cells and to cells transfected with the plasmid containing the neomycin resistance gene only.It was found that EGF(10ng/ml) had an augmenation effect on the growth of transfected MDA-AS10 cells but not MDA-MB-231 cells.Flow cytometric analysis showed that the cell cycle of the transfected cells was abnormal with a decrease of cells in G2/M and S phases and an increase of cells in G1 phase,indicating a blockage in phase G1.Immunofluorescence of EGFR expression in transfectants stained with an antiEGFR antibody was decreased and their growth in soft agarose was also severely imparired.The transfected cells showed less adherence to laminin(LN) and fibronectin (FN).In short,EGFR antisense RNA decreases the expression of EGFR on MDA-MB-231 cells and partially reverses their malignant phenotype as well.

  1. Studies of TBX4 and chromosome 17q23.1q23.2: an uncommon cause of nonsyndromic clubfoot

    Science.gov (United States)

    Lu, W.; Bacino, C. A.; Richards, B.S.; Alvarez, C.; VanderMeer, J.E.; Vella, M.; Ahituv, N.; Sikka, N.; Dietz, F.R.; Blanton, S.H.; Hecht, J.T.

    2012-01-01

    Clubfoot is a common birth defect characterized by inward posturing and rigid downward displacement of one or both feet. The etiology of syndromic forms of clubfoot is varied and the causes of isolated clubfoot are not well understood. A microduplication of 2.2 Mb on chromosome 17q23.1q23.2 which includes T-box 4 (TBX4), a hindlimb-specific gene, and 16 other genes was recently identified in 3 of 66 families reported as nonsyndromic clubfoot, but additional non-foot malformations place them in the syndromic clubfoot category. Our study assesses whether variation in or around TBX4 contributes to nonsyndromic clubfoot. To determine whether this microduplication was a common cause of nonsyndromic clubfoot, 605 probands (from 148 multiplex and 457 simplex families) with nonsyndromic clubfoot were evaluated by copy number and oligonucleotide array CGH testing modalities. Only one multiplex family (0.68%) that had 16 with clubfoot and 9 with other foot anomalies, had a 350kb microduplication, which included the complete duplication of TBX4 and NACA2 and partial duplication of BRIP1. The microduplication was transmitted in an autosomal dominant pattern and all with the microduplication had a range of phenotypes from short wide feet and toes to bilateral clubfoot. Minimal evidence was found for an association between TBX4 and clubfoot and no pathogenic sequence variants were identified in the two known TBX4 hindlimb enhancer elements. Altogether, these results demonstrate that variation in and around the TBX4 gene and the 17q23.1q23.2 microduplication are not a frequent cause of this common orthopedic birth defect and narrows the 17q23.1q23.2 nonsyndromic clubfoot-associated region. PMID:22678995

  2. Comparative proteomic analysis implicates eEF2 as a novel target of PI3Kγ in the MDA-MB-231 metastatic breast cancer cell line

    Directory of Open Access Journals (Sweden)

    Niu Meizhi

    2013-01-01

    Full Text Available Abstract Background Cancer cell migration is fundamentally required for breast tumour invasion and metastasis. The insulin-like growth factor 1 tyrosine kinase receptor (IGF-1R and the chemokine G-protein coupled receptor, CXCR4 have been shown to play an important role in breast cancer metastasis. Our previous study has shown that IGF-1R can transactivate CXCR4 via a physical association in the human MDA-MB-231 metastatic breast cancer cell line and that this plays a key role in IGF-I-induced migration of these cells. In the present study we used pharmacological inhibition and RNAi to identify PI3Kγ as an important migration signalling molecule downstream of receptor transactivation in MDA-MB-231 cells. To identify PI3Kγ-regulated proteins upon transactivation of CXCR4 by IGF-I, we undertook a comparative proteomics approach using 2-D- Fluorescence Difference Gel Electrophoresis (DIGE and identified the proteins by mass spectrometry. Results These experiments identified eukaryotic elongation factor 2 (eEF2 as a novel downstream target of PI3Kγ after activation of the IGF-1R-CXCR4 heterodimer by IGF-I. Further analysis demonstrated that eEF2 is phosphorylated in MDA-MB-231 cells in response to IGF-I and that this is dependent on PI3Kγ activity. Conclusions Our data imply a novel role for PI3Kγ in facilitating cell migration by regulating phosphorylation of eEF2.

  3. IL DECRETO LEGISLATIVO N. 231/2001 ALLA PROVA DEI REATI AMBIENTALI. Aspetti problematici di ascrizione della responsabilità all’ente.

    OpenAIRE

    Casellato, Marco

    2014-01-01

    My Phd research is focused on the theme of the extension of the corporate liability to environmental crimes. This “reform” has been realized by the legislative decree n. 121/2011 on which also corporations are responsible for environmental offences, as provided by the art. 25 undecies of the legislative decree n. 231/2001. The new statutory legislation puts into effect the European regulation: the EU directive 2008/99/CE on the protection of the environment through Criminal law, and the on...

  4. High resolution measurement of the /sup 231/Pa(n,f) cross section from 0. 4 eV to 12 MeV

    Energy Technology Data Exchange (ETDEWEB)

    Plattard, S; Auchampaugh, G F; de Saussure, G

    1980-01-01

    The /sup 231/Pa(n,f) reaction was studied to shed light on the existence of a shallow third minimum in the /sup 232/Pa fission barrier. Results are plotted along with data points derived from ENDF/B-V. The occurrence of a pure vibrational state at E/sub n/ = 156.7 keV (3/sup +/) together with a nearby state of opposite parity favors the evidence for a third asymmetrically deformed minimum in the /sup 232/Pa fission barrier. 2 figures. (RWR)

  5. MicroRNA-125b Induces Metastasis by Targeting STARD13 in MCF-7 and MDA-MB-231 Breast Cancer Cells

    OpenAIRE

    Feng Tang; Rui Zhang; Yunmian He; Meijuan Zou; Le Guo; Tao Xi

    2012-01-01

    MicroRNAs (miRNAs) are a class of small noncoding RNAs that regulate gene expression by targeting mRNAs to trigger either translation repression or mRNA degradation. miR-125b is down-regulated in human breast cancer cells compared with the normal ones except highly metastatic tumor cells MDA-MB-231. However, few functional studies were designed to investigate metastatic potential of miR-125b. In this study, the effects of miR-125b on metastasis in human breast cancer cells were studied, and t...

  6. Antitumor Function of Compound Polysaccharides from Spirulina Platensis on Human MB-231 Cell Line in Vitro%复合螺旋藻多糖对人乳腺癌MB-231细胞株体外抗肿瘤作用研究

    Institute of Scientific and Technical Information of China (English)

    徐小娟; 张勇; 唐超; 葛蔚; 刘永举; 王清吉

    2012-01-01

    目的:研究复合螺旋藻多糖对体外培养的人乳腺癌MB-231肿瘤细胞的抑制作用及可能的作用机制.方法:以人乳腺癌MB-231细胞株为研究对象,将螺旋藻多糖(PSP)与银杏叶提取物(GBE)按不同比例复合,并用不同浓度的复合制剂分别对细胞作用后,分别在48h、72h后,显微镜下观察细胞形态学变化,MTT法测其生长抑制率.48h后,PI及AnnexinV-FITC/PI染色,用流式细胞仪测其细胞周期及凋亡率.结果:复合螺旋藻多糖对人乳腺癌MB-231细胞均有不同程度的抑制作用,复合组优于单一成分组,抑制生长效果与时间和剂量呈依赖关系;将人乳腺癌MB-231细胞阻滞于G0 /G1期,抑制肿瘤细胞的有丝分裂;促进肿瘤细胞凋亡,与空白组相比差异显著.结论:复合螺旋藻多糖通过阻断细胞周期达到抑制体外培养的人乳腺癌MB-231细胞的生长的目的,具有较好的抗肿瘤活性.%Objective : To explore the inhibitory effects and possible mechanisms of compound polysaccharides from Spirulina Platensis ( PSP ) on human mammary cancer 231eells in vitro. Methods : Cells were treated with different concentrations of polysaeoharide.s from Spirulina Platensis compounded with Ginkgo Biloba Extract ( GBE ) at different ratios. After 48h and 72h, the morphological changes of cells were observed under microscope, cytotoxic effects were evaluated by MTT method. After 48h cells were stained with PI and AnnexinV -FITC/PI, the cell cycle and apoptosis ratio were measured by flow cytometry. Results: Compound polysaccharides from Spirulina Platensis of different ratio were cytotoxic to MB-231 cells in a time and dose dependent manner. And the inhibitory rates of them were higher than that of the single groups. The proportion of MB-23 lcells in GO /G1 phase was significantly increased. The mitosis of tumor cells was inhibited. The apoptosis rate of compound groups were remarkably increased compared with that in blank control group

  7. 乌司他丁和泰索帝对人乳腺癌细胞MDA-MB-231增殖和侵袭的影响及其机制%Effect of Ulinastatin and Taxotere on Proliferation and Invasion of Human Breast Cancer Line MDA-MB-231 Ce1Ps and Relevant Mechanism

    Institute of Scientific and Technical Information of China (English)

    赵晓亮; 孙治君; 罗杰; 高峰

    2011-01-01

    Objective To observe the effect of ulinastatin (ULI)and taxotere (TXT) on proliferation and invasion of human breast cancer MDA-MB-231 cells as well as expressions of IL-6, IL-8 and TNF-α.Methods The estrogen receptor-negative MDAMB-231 cells cultured in vitro were randomly divided into blank control, ULI (800 U/mi), TXT (3.7 μg/ml) and ULI + TXT groups, and determined for the transcription levels of IL-6, IL-8 and TNF-α mRNAs by fluorescent quantitative RT-PCR, for proliferation ability by MTF method, and for invasion ability by Transwell chamber assay.Results Both TXT and ULI inhibited the expressions of IL-6, IL-8 and TNF-α genes as well as the proliferation and invasion of MDA-MB-231 cells, while the inhibition ability of ULI was lower than that of TXT.However, TXT combined with ULI showed the strongest inhibitory effect in all the four groups.Conclusion ULI inhibited the proliferation and invasion of human breast cancer MDA-MB-231 cells by a mechanism which might be associated with the down-regulation of expressions of IL-6, IL-8 and TNF-α genes.%目的 探讨乌司他丁(Ulinastatin,ULI)和泰索帝(Taxotere,TXT)对人乳腺癌细胞MDA-MB-231增殖、侵袭及白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)表达的影响.方法 将体外培养的人乳腺癌细胞MDA-MB-231(雌激素受体阴性)随机分为4组:对照组、ULI组(800 U/ml),TXT组(3.7 Rg/ml)和ULI+TXT组,采用荧光定量RT-PCR法检测细胞IL-6、IL-8和TNF-α基因mRNA的转录水平;MTT法检测细胞的增殖能力;TransweⅡ小室侵袭试验检测细胞的浸润能力.结果 TXT和ULI均能抑制MDA-MB-231细胞IL-6、IL-8和TNF-α基因的表达及细胞的增殖和侵袭能力,ULI的抑制作用低于TXT,但TXT与ULI联合应用,抑制作用最强.结论 ULI能抑制人乳腺癌细胞MDA-MB-231的增殖、侵袭,其作用机制可能与ULI降低IL-6、IL-8及TNF-α基因的表达有关.

  8. Effect of lupeol on migration and invasion of human breast cancer MDA-MB-231 cells and its mechanism%羽扇豆醇对人乳腺癌MDA-MB-231细胞侵袭转移作用及机制研究

    Institute of Scientific and Technical Information of China (English)

    王明; 崔红霞; 孙超; 李刚; 王宏兰; 夏春辉; 王玉春; 刘吉成

    2016-01-01

    探索狼毒大戟活性成分羽扇豆醇(lupeol)对人乳腺癌MDA-MB-231细胞侵袭转移的作用,并对其机制进行研究.采用细胞黏附实验、transwell侵袭实验和伤口愈合细胞划痕实验检测羽扇豆醇对人乳腺癌MDA-MB-231细胞侵袭转移能力的作用.Western blot法测定不同浓度羽扇豆醇处理人乳腺癌后,侵袭转移相关蛋白环氧化酶2 (COX-2)、金属基质蛋白-2(MMP-2)、MMP-9和NF-κB p65的表达.结果显示,羽扇豆醇对人乳腺癌MDA-MB-231细胞的黏附、迁移和侵袭有明显的抑制作用,并具有一定的量效关系,且相关蛋白COX-2、MMP-2、MMP-9和NF-κB p65的表达均下调.由此可见,羽扇豆醇在体外能够有效地抑制人乳腺癌MDA-MB-231细胞的侵袭和转移,可能与抑制COX-2、MMP-2和MMP-9的蛋白表达有关,其机制可能是抑制了核转录因子NF-κB信号途径.

  9. 5-氮杂-2'-脱氧胞苷序贯顺铂对MDA-MB-231细胞的影响%Effect of sequential treatment of 5-aza-2'-deoxycytidine and cisplatin in MDA-MB-231 cells

    Institute of Scientific and Technical Information of China (English)

    沈三弟; 陈卓荣; 肖高芳; 刘彦明; 黄湛; 罗智辉

    2013-01-01

    目的 探讨5-氮杂-2'-脱氧胞苷(DAC)、顺铂(PDD)序贯应用对人三阴性乳腺癌细胞MDA-MB-231体外增殖、周期及凋亡的影响.方法 实验分4组:对照组、DAC组(5μmol/L DAC处理)、PDD组(15 μmol/L PDD处理)、DAC序贯PDD组(2.5μmol/L DAC处理24h,再用8μmol/L PDD处理48 h).分别用MTT法、流式细胞仪测定各组MDA-MB-231细胞的增殖、周期及凋亡,并用金氏公式来评价两药联合效应.结果 DAC序贯PDD组较DAC组、PDD组增殖抑制率高(P<0.01).DAC序贯PDD组48 h、72 h的q值分别为1.12、1.17,两药联合有增效作用.DAC序贯PDD组G1、S期细胞减少,G2/M期细胞增多,DAC序贯PDD组较DAC组、PDD组细胞凋亡率高(P<0.01).结论 低剂量的DAC与PDD序贯应用可以抑制人三阴性乳腺癌MDA-MB-231细胞增殖,促进MDA-MB-231细胞凋亡.

  10. The important role of Gli-1 in hypoxia-induced epithelial-mesenchymal transition of breast cancer cell line MDA-MB-231%Gli-1在缺氧诱导乳腺癌MDA-MB-231细胞上皮-间质转分化中的重要作用

    Institute of Scientific and Technical Information of China (English)

    李徐奇; 雷建军; 徐勤鸿; 段万星; 盛薇; 王康; 魏光兵

    2014-01-01

    目的 探讨Gli-1在缺氧诱导乳腺癌MDA-MB-231细胞上皮-间质转分化(EMT)及侵袭中的重要作用.方法 通过缺氧培养乳腺癌MDA-MB-231细胞,以常氧培养作为对照.Transwell小室侵袭试验检测各组MDA-MB-231细胞的侵袭能力;Western blot检测HIF-1α、Gli-1、E-Cadherin和vimentin蛋白的表达水平.通过shRNA稳定转染乳腺癌细胞,再次通过Transwell小室侵袭试验检测缺氧对乳腺癌细胞侵袭能力的影响,Western blot检测HIF 1α、Gli-1、E-Cadherin和vimentin蛋白的表达水平.结果 缺氧可明显诱导乳腺癌MDA MB-231细胞侵袭,并上调HIF-1α、Gli-1和vimentin蛋白,下调E-cadherin蛋白.靶向沉默Gli-1基因后,缺氧失去了对乳腺癌细胞侵袭和EMT的诱导作用.结论 缺氧通过上调Gli-1表达活化Hedgehog通路,诱导乳腺癌细胞侵袭及EMT过程.

  11. Effect of chidamide in combination with cisplatin interventing proliferation in triple-negative breast cancer cell lines MDA-MB-231 in vitro and its mechanism research%西达本胺联合顺铂对三阴乳腺癌细胞株MDA-MB-231的体外抗增殖作用及其机制的研究

    Institute of Scientific and Technical Information of China (English)

    项丹; 姜藻; 顾晓怡

    2013-01-01

    Objective: To explore the chidamide in combination with cisplatin on three negative breast cancer cells MDA-MB-231 inhibition and its possible molecular mechanism. Methods; The separate and combined administration with MTT method for the determination of MDA-MB-231 cell proliferation , flow cytometry ( FCM ) examination apoptosis rate , analysis of Western blotting acetylation of histone H 3 and HDAC3 expression levels , fluorescence quantitative PCR detection of ERCC1 expression level . Results; The detection of MTT showed that chidamide monotherapy and cisplatin monotherapy for in vitro cell line MDA-MB-231 value has certain inhibitory action in a dose-and time-dependent manner. Combined medication can play a synergistic effect. Chidamide can inhibit MDA-MB-231 cell HDAC3 expression, increased histone H3 acetylation levels. The synergistic effect combined with cisplatin of molecular mechanism is to decrease the expression of ERCC 1. Conclusion; Chidamide in combination with cisplatin in vitro may synergistically inhibit the proliferation of TNBC cell lines MDA -MB-231.%目的:探讨西达本胺联合顺铂对三阴乳腺癌细胞株MDA-MB-231的抑制作用及其可能的分子机制.方法:单独及联合给药后采用MTT法测定MDA-MB-231细胞的增殖,流式细胞仪(FCM)检测细胞凋亡率,Western blotting法分析乙酰化组蛋白H3及HDAC3的表达水平,荧光定量PCR检测ERCC1表达水平.结果:MTT法检测发现,西达本胺单药和顺铂单药在体外对细胞株MDA-MB-231增殖都有一定的抑制作用,且呈浓度、时间依赖性;联合用药可起到协同效应.西达本胺可抑制MDA-MB-231细胞株HDAC3的表达,提高组蛋白H3的乙酰化水平.联合顺铂起到协同效应的分子机制主要是降低细胞株ERCC1的表达水平.结论:西达本胺联合顺铂在体外能协同抑制三阴乳腺癌细胞株MDA-MB-231的增殖.

  12. Effects of Chinese medicinal herbs on expression of brain-derived Neurotrophic factor (BDNF) and its interaction with human breast cancer MDA-MB-231 cells and endothelial HUVECs.

    Science.gov (United States)

    Chiu, Jen-Hwey; Chen, Fang-Pey; Tsai, Yi-Fang; Lin, Man-Ting; Tseng, Ling-Ming; Shyr, Yi-Ming

    2017-08-12

    Our previous study demonstrated that an up-regulation of the Brain-Derived Neurotrophic Factor (BDNF) signaling pathway is involved the mechanism causing the recurrence of triple negative breast cancer. The aim of this study is to investigate the effects of commonly used Chinese medicinal herbs on MDA-MB-231 and HUVEC cells and how they interact with BDNF. Human TNBC MDA-MB-231 cells and human endothelial HUVEC cells were used to explore the effect of commonly used Chinese herbal medicines on cancer cells alone, on endothelial cells alone and on cancer cell/endothelial cell interactions; this was done via functional studies, including migration and invasion assays. Furthermore, Western blot analysis and real-time PCR investigations were also used to investigate migration signal transduction, invasion signal transduction, and angiogenic signal transduction in these systems. Finally, the effect of the Chinese medicinal herbs on cancer cell/endothelial cell interactions was assessed using co-culture and ELISA. In terms of autoregulation, BDNF up-regulated TrkB gene expression in both MDA-MB-231 and HUVEC cells. Furthermore, BDNF enhanced migration by MDA-MB-231 cells via Rac, Cdc42 and MMP, while also increasing the migration of HUVEC cells via MMP and COX-2 expression. As measured by ELISA, the Chinese herbal medicinal herbs A. membranaceus, P. lactiflora, L. chuanxiong, P. suffruticosa and L. lucidum increased BDNF secretion by MDA-MB-231 cells. Similarly, using a co-culture system with MDA-MB-231 cells, A. membranaceus and L. lucidum modulated BDNF-TrkB signaling by HUVEC cells. We conclude that BDNF plays an important role in the metastatic interaction between MDA-MB-231 and HUVEC cells. Some Chinese medicinal herbs are able to enhance the BDNF-related metastatic potential of the interaction between cancer cells and endothelial cells. These findings provide important information that should help with the development of integrated medical therapies for breast

  13. The anti-proliferative effect of metformin in triple-negative MDA-MB-231 breast cancer cells is highly dependent on glucose concentration: implications for cancer therapy and prevention.

    Science.gov (United States)

    Zordoky, Beshay N M; Bark, Diana; Soltys, Carrie L; Sung, Miranda M; Dyck, Jason R B

    2014-06-01

    Metformin has been shown to have a strong anti-proliferative effect in many breast cancer cell lines, mainly due to the activation of the energy sensing kinase, AMP-activated protein kinase (AMPK). MDA-MB-231 cells are aggressive and invasive breast cancer cells that are known to be resistant to several anti-cancer agents as well as to the anti-proliferative effect of metformin. As metformin is a glucose lowering drug, we hypothesized that normoglycemia will sensitize MDA-MB-231 cells to the anti-proliferative effect of metformin. MDA-MB-231 cells were treated with increasing metformin concentrations in hyperglycemic or normoglycemic conditions. The growth inhibitory effect of metformin was assessed by MTT assay. The expression of several proteins involved in cell proliferation was measured by Western blotting. In agreement with previous studies, treatment with metformin did not inhibit the growth of MDA-MB-231 cells cultured in hyperglycemic conditions. However, metformin significantly inhibited MDA-MB-231 growth when the cells were cultured in normoglycemic conditions. In addition, we show that metformin-treatment of MDA-MB-231 cells cultured in normoglycemic conditions and not in hyperglycemic conditions caused a striking activation of AMPK, and an AMPK-dependent inhibition of multiple molecular signaling pathways known to control protein synthesis and cell proliferation. Our data show that normoglycemia sensitizes the triple negative MDA-MB-231 breast cancer cells to the anti-proliferative effect of metformin through an AMPK-dependent mechanism. These findings suggest that tight normoglycemic control may enhance the anti-proliferative effect of metformin in diabetic cancer patients. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Effects of exogenous zinc on cell cycle, apoptosis and viability of MDAMB231, HepG2 and 293 T cells.

    Science.gov (United States)

    Wang, Yan-hong; Li, Ke-jin; Mao, Li; Hu, Xin; Zhao, Wen-jie; Hu, An; Lian, Hong-zhen; Zheng, Wei-juan

    2013-09-01

    As a non-toxic metal to humans, zinc is essential for cell proliferation, differentiation, regulation of DNA synthesis, genomic stability and mitosis. Zinc homeostasis in cells, which is crucial for normal cellular functioning, is maintained by various protein families including ZnT (zinc transporter/SLC30A) and ZIP (Zrt-, Irt-like proteins/SLC39A) that decrease and increase cytosolic zinc availability, respectively. In this study, we investigated the influences of a specific concentration range of ZnSO4 on cell cycle and apoptosis by flow cytometry, and cell viability by MTT method in MDAMB231, HepG2 and 293 T cell lines. Fluorescent sensors NBD-TPEA and the counterstain for nuclei Hoechst 33342 were used to stain the treated cells for observing the localisation and amount of Zn(2+) via laser scanning confocal microscope. It was found that the influence manners of ZnSO4 on cell cycle, apoptosis and cell viability in various cell lines were different and corresponding to the changes of Zn(2+) content of the three cell lines, respectively. The significant increase on intracelluar zinc content of MDAMB231 cells resulted in cell death, G1 and G2/M cell cycle arrest and increased apoptotic fraction. Additionally, the mRNA expression levels of ZnT and ZIP families in the three cell lines, when treated with high concentration of ZnSO4, increased and decreased corresponding to their functions, respectively.

  15. LINE-1 ORF-1p functions as a novel HGF/ETS-1 signaling pathway co-activator and promotes the growth of MDA-MB-231 cell.

    Science.gov (United States)

    Yang, Qian; Feng, Fan; Zhang, Fan; Wang, Chunping; Lu, Yinying; Gao, Xudong; Zhu, Yunfeng; Yang, Yongping

    2013-12-01

    Long interspersed nucleotide element (LINE)-1 ORF-1p is encoded by the human pro-oncogene LINE-1. It is involved in the development and progression of several human carcinomas, such as hepatocellular carcinoma and lung and breast cancers. The hepatocyte growth factor (HGF)/ETS-1 signaling pathway is involved in regulation of cancer cell proliferation, metastasis and invasion. The biological function of the interaction between LINE-1 ORF-1p and the HGF/ETS-1 signaling pathway in regulation of human breast cancer proliferation remains largely unknown. Here, we showed that LINE-1 ORF-1p enhanced ETS-1 transcriptional activity and increased expression of downstream genes of ETS-1. Interaction between ETS-1 and LINE-1 ORF-1p was identified by immunoprecipitation assays. LINE-1 ORF-1p modulated ETS-1 activity through cytoplasm/nucleus translocation and recruitment to the ETS-1 binding element in the MMP1 gene promoter. We also showed that LINE-1 ORF-1p promoted proliferation and anchorage-independent growth of MDA-MB-231 breast cancer cells. By investigating a novel role of the LINE-1 ORF-1p in the HGF/ETS-1 signaling pathway and MDA-MB-231 cells, we demonstrated that LINE-1 ORF-1p may be a novel ETS-1 coactivator and molecular target for therapy of human triple negative breast cancer. © 2013.

  16. High resolution observations of HCN and HCO+ J=3-2 in the disk and outflow of Mrk231 -Detection of vibrationally excited HCN in the warped nucleus

    CERN Document Server

    Aalto, S; Muller, S; Winters, J M; Gonzalez-Alfonso, E; van der Werf, P; Henkel, C; Costagliola, F; Neri, R

    2014-01-01

    We obtained high resolution (0."25 to 0."90) observations of HCN and HCO+ J=3-2 of the ultraluminous QSO galaxy Mrk231 with the IRAM Plateau de Bure Interferometer. We find luminous HCN and HCO+ 3-2 emission in the main disk and we detect compact (r350 pc) line wings are found for HCN 3-2 with velocities +-750 km/s. Line ratios indicate that the emission is emerging in dense gas n=1e4 - 5e5 cm-3 of elevated HCN abundance X(HCN)=1e-8 to 1e-6. High X(HCN) also allows for the emission to originate in gas of more moderate density. We tentatively detect nuclear emission from the reactive ion HOC+ with HCO+/HOC+=10-20. The HCN v2=1f line emission is consistent with the notion of a hot, dusty, warped inner disk of Mrk231 where the v2=1f line is excited by bright mid-IR 14 micron continuum. We estimate the vibrational temperature T_vib to 200-400 K. We propose that 50% of the main HCN emission may have its excitation affected by the radiation field through IR pumping of the vibrational ground state. The HCN emission ...

  17. Antiproliferative activity of Alisol B in MDA-MB-231 cells is mediated by apoptosis, dysregulation of mitochondrial functions, cell cycle arrest and generation of reactive oxygen species.

    Science.gov (United States)

    Zhang, Aifeng; Sheng, Yuqing; Zou, Mingchang

    2017-03-01

    Previous studies have demonstrated that Alisol B has inhibitory activity in cancer cells. However, the exact mechanism through which inhibition is achieved is still poorly understood. In the present study, the authors examined the effects of Alisol B in human breast cancer cells. Alisol B showed significant anticancer activity in MDA-MB-231 cells. The results demonstrated that the cytotoxicity induced by Alisol B was mediated by induction of apoptosis, decrease in mitochondrial membrane potential, cell cycle arrest, activation of caspases and accumulation of ROS (reactive oxygen species) level. Interestingly, pretreatment of cells with the general caspase inhibitor z-VAD-FMK significantly prevented Alisol B-induced apoptosis. Furthermore, western blot analysis revealed the upregulation of p-p38 and downregulation of p-AKT, p-p65 and p-mTOR. Taken together, the above results suggest that Alisol B suppresses the growth of MDA-MB-231 cells mainly through induction of apoptosis; this outcome may represent the major mechanism of Alisol B-mediated apoptosis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  18. Fucoidan Extract Enhances the Anti-Cancer Activity of Chemotherapeutic Agents in MDA-MB-231 and MCF-7 Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Zhongyuan Zhang

    2013-01-01

    Full Text Available Fucoidan, a fucose-rich polysaccharide isolated from brown alga, is currently under investigation as a new anti-cancer compound. In the present study, fucoidan extract (FE from Cladosiphon navae-caledoniae Kylin was prepared by enzymatic digestion. We investigated whether a combination of FE with cisplatin, tamoxifen or paclitaxel had the potential to improve the therapeutic efficacy of cancer treatment. These co-treatments significantly induced cell growth inhibition, apoptosis, as well as cell cycle modifications in MDA-MB-231 and MCF-7 cells. FE enhanced apoptosis in cancer cells that responded to treatment with three chemotherapeutic drugs with downregulation of the anti-apoptotic proteins Bcl-xL and Mcl-1. The combination treatments led to an obvious decrease in the phosphorylation of ERK and Akt in MDA-MB-231 cells, but increased the phosphorylation of ERK in MCF-7 cells. In addition, we observed that combination treatments enhanced intracellular ROS levels and reduced glutathione (GSH levels in breast cancer cells, suggesting that induction of oxidative stress was an important event in the cell death induced by the combination treatments.

  19. Daucus carota pentane-based fractions arrest the cell cycle and increase apoptosis in MDA-MB-231 breast cancer cells.

    Science.gov (United States)

    Shebaby, Wassim N; Mroueh, Mohammad; Bodman-Smith, Kikki; Mansour, Anthony; Taleb, Robin I; Daher, Costantine F; El-Sibai, Mirvat

    2014-10-10

    Daucus carota L.ssp.carota (wild carrot), an herb used in folk medicine worldwide, was recently demonstrated to exhibit anticancer activity. In this study we examined the anticancer effect of Daucus carota oil extract (DCOE) fractions on the human breast adenocarcinoma cell lines MDA-MB-231 and MCF-7 and clarified the mechanism of action. Using the WST assay, the pentane fraction (F1) and 1:1 pentane:diethyl ether fraction (F2) were shown to possess the highest cytotoxicity against both cell lines. Flow cytometric analysis revealed that both fractions induced the accumulation of cells in the sub-G1 phase, increase in apoptotic cell death and chromatin condensation. The increase in apoptosis in response to treatment was also apparent in the increase in BAX and the decrease in Bcl-2 levels as well as the proteolytic cleavage of both caspase-3 and PARP as revealed by Western blot. Furthermore, treatment of MDA-MB-231 cells with either fraction significantly reduced the level of phosphorylated Erk but did not show any effect on phosphorylated Akt. The combined treatment with a potent PI3K inhibitor (wortmannin) and F1 or F2 fraction had a synergistic inhibitory effect on cell survival which shows that these two drugs work on different pathways. These results suggest that the pentane-based fractions of DCOE possess potential anti-cancer activity that is mainly mediated through the Erk pathway.

  20. Induction of acetylation and bundling of cellular microtubules by 9-(4-vinylphenyl) noscapine elicits S-phase arrest in MDA-MB-231 cells.

    Science.gov (United States)

    Cheriyamundath, Sanith; Mahaddalkar, Tejashree; Kantevari, Srinivas; Lopus, Manu

    2017-02-01

    Noscapine is an alkaloid present in the latex of Papaver somniferum. It has been known for its anticancer efficacy and lack of severe toxicities to normal tissues. Structural alterations in noscapine core architecture have produced a number of potent analogues of noscapine. Here, we report an unusual activity of a novel noscapine analogue, 9-(4-vinylphenyl)noscapine (VinPhe-Nos) on cancer cells. As we reported earlier, VinPhe-Nos inhibited MDA-MB-231 cell proliferation with an IC50 of 6μM. The present study elucidated a possible antiproliferative mechanism of action of VinPhe-Nos. The noscapinoid significantly inhibited clonogenic propagation of MDA-MB-231 cells. However, unlike the majority of tubulin-binding agents, it did not induce mitotic arrest; instead, it prolonged S-phase. Although prolonged presence of the drug show some disruption of cellular microtubule architecture, it did not affect microtubule recovery after cold-induced depolymerization. VinPhe-Nos, nevertheless, induced acetylation and bundling of microtubules. Our data suggest that rational modification of parent compound can alter its mechanism of action on cell cycle and that VinPhe-Nos can be investigated further as a less-toxic, S-phase-preferred, cytostatic anticancer agent.

  1. Effects of cadmium chloride on some mitochondria-related activity and gene expression of human MDA-MB231 breast tumor cells.

    Science.gov (United States)

    Cannino, Giuseppe; Ferruggia, Elisa; Luparello, Claudio; Rinaldi, Anna Maria

    2008-08-01

    It was reported that cadmium is able to exert a cytotoxic effect on tumor MDA-MB231 cells, which shows signs of "non-classical" apoptosis and is characterized by drastic changes in gene expression pattern. In this study, we have extended our knowledge of metal-breast cancer cell interactions by analyzing some mitochondria-related aspects of the stress response to CdCl(2) at either 5 or 50 microM 24- or 96-h exposure, by cytochemical, conventional PCR and Northern/Western blot techniques. We demonstrated that (i) no modification of the mitochondrial mass was detectable due to CdCl(2) exposure; (ii) the respiration activity appeared to be increased after 96-h exposures, while the production of reactive oxygen species was significantly induced, as well; (iii) hsp60, hsp70, COXII and COXIV expressions were dependent on the duration of Cd exposure; (iv) a different hsp60 protein distribution was observed in mitochondrial and post-mitochondrial extracts and (v) 96-h exposure induced the over-expression of hsc/hsp70 proteins and, conversely, the down-regulation of cytochrome oxidase subunits II and IV. These observations, in addition to providing more information on the cellular and molecular aspects of the interaction between CdCl(2) and MDA-MB231 breast tumor cells, contribute to the comprehension of the intracellular molecular mechanisms implicated in the regulation of some mitochondrial proteins.

  2. Exposure to cadmium chloride influences astrocyte-elevated gene-1 (AEG-1) expression in MDA-MB231 human breast cancer cells.

    Science.gov (United States)

    Luparello, Claudio; Longo, Alessandra; Vetrano, Marco

    2012-01-01

    It is known that cadmium (Cd) is able to regulate gene expression, drastically affecting the pattern of transcriptional activity and intracellular signalization in normal and pathological human cells. We have already shown that Cd exerts a cytotoxic effect on neoplastic MDA-MB231 cells from the human breast, which is characterized by the onset of a "non-classical" apoptotic kind of death, impairment of mitochondrial activity and drastic changes in gene expression pattern. In the present study, employing a combination of conventional and differential display-PCR techniques, immunocytochemical, ELISA and Western analyses, we extended the knowledge on the transcriptional modulation exerted by the metal demonstrating that in MDA-MB231 cells 5 μM CdCl(2) treatment for 96 h selectively down-regulates astrocyte-elevated gene-1 (AEG-1) and reduces the accumulation of its protein product which appears to be associated with the internal cytomembranes and also present in the nucleoplasm. In addition, due to the acknowledged role of AEG-1 in the intranuclear shuttling of NF-κB p65 subunit, we also showed that CdCl(2) treatment determines the decrease of p65 amount in nuclear extracts and the down-regulation of the NF-κB downstream genes c-fos and c-jun, thus providing a new contribution to the comprehension of the intracellular molecular mechanisms implicated in Cd-breast cancer cell interactions.

  3. Effect of transfection with PLP2 antisense oligonucleotides on gene expression of cadmium-treated MDA-MB231 breast cancer cells.

    Science.gov (United States)

    Longo, Alessandra; Librizzi, Mariangela; Luparello, Claudio

    2013-02-01

    Emerging evidence indicates that cadmium (Cd) is able to regulate gene expression, drastically affecting the pattern of transcriptional activity in human normal and pathological cells. We have already shown that exposure of MDA-MB231 breast cancer cells to 5 μM CdCl(2) for 96 h, apart from significantly affecting mitochondrial metabolism, induces modifications of the expression level of genes coding for members of stress response-, mitochondrial respiration-, MAP kinase-, NF-κB-, and apoptosis-related pathways. In the present study, we have expanded the knowledge on the biological effects of Cd-breast cancer cell interactions, indicating PLP2 (proteolipid protein-2) as a novel member of the list of Cd-upregulated genes by MDA-MB231 cancer cells and, through the application of transfection techniques with specific antisense oligonucleotides, we have demonstrated that such over-expression may be an upstream event to some of the changes of gene expression levels already observed in Cd-treated cells, thus unveiling new possible molecular relationship between PLP2 and genes linked to the stress and apoptotic responses.

  4. Estrogenic Activity of Some Phytoestrogens on Bovine Oxytocin and Thymidine Kinase-ERE Promoter through Estrogen Receptor-α in MDA-MB 231 Cells

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    Ehsan Zayerzadeh

    2014-08-01

    Full Text Available Background: Phytoestrogens, a group of plant-derived polyphenolic compounds have recently come into considerable attention due to the increasing information on their potential adverse effects in human health. Some of phytoestrogens show estrogenic activity that may be carcinogenic for human. In the present study, we investigated the transcriptional effects of variety of phytoestrogens on the bovine oxytocin and the thymidine kinase-ERE promoter by estrogen receptor α in MDA-MB 231 breast cancer cell line. Materials and Methods: Cells were seeded for transfections into 12- well plates at a density of 100000 cells per well were transfected with a total of 3 μg of plasmid DNA using calcium phosphate coprecipitation. Estrogen and some phytoestrogens (naringenin, 8-prenyl-naringenin and 6-( 1, 1 - dimethylallyl naringenin were used for the stimulation of transfected cells. Results: Findings of our study clearly demonstrated the subtype-selective activation of estrogen receptor (ERα and (ERβ by the p hytoestrogen naringenin (activating estrogen receptor β and its substituted forms 8-prenyl-naringenin and 6-( 1, 1 - dimethylallyl naringenin (activating estrogen receptor α , on the ERE-controlled promoter as well as on the oxytocin gene promoter. Conclusion: The study revealed that some p hytoestrogen s show estrogenic activity by classical or non-classical mechanisms as well as exhibit estrogenic activity by undetermined mechanisms in transfected MDA-MB 231 cell line.

  5. Small molecule inhibition of arylamine N-acetyltransferase Type I inhibits proliferation and invasiveness of MDA-MB-231 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Tiang, Jacky M. [School of Biomedical Sciences, University of Queensland, St. Lucia, Qld 4072 (Australia); Butcher, Neville J., E-mail: n.butcher@uq.edu.au [School of Biomedical Sciences, University of Queensland, St. Lucia, Qld 4072 (Australia); Minchin, Rodney F. [School of Biomedical Sciences, University of Queensland, St. Lucia, Qld 4072 (Australia)

    2010-02-26

    Arylamine N-acetyltransferase 1 is a phase II metabolizing enzyme that has been associated with certain breast cancer subtypes. While it has been linked to breast cancer risk because of its role in the metabolic activation and detoxification of carcinogens, recent studies have suggested it may be important in cell growth and survival. To address the possible importance of NAT1 in breast cancer, we have used a novel small molecule inhibitor (Rhod-o-hp) of the enzyme to examine growth and invasion of the breast adenocarcinoma line MDA-MB-231. The inhibitor significantly reduced cell growth by increasing the percent of cells in G2/M phase of the cell cycle. Rhod-o-hp also reduced the ability of the MDA-MB-231 cells to grow in soft agar. Using an in vitro invasion assay, the inhibitor significantly reduced the invasiveness of the cells. To test whether this effect was due to inhibition of NAT1, the enzyme was knocked down using a lentivirus-based shRNA approach and invasion potential was significantly reduced. Taken together, the results of this study demonstrate that NAT1 activity may be important in breast cancer growth and metastasis. The study suggests that NAT1 is a novel target for breast cancer treatment.

  6. Antiproliferative effect of gold(I compound auranofin through inhibition of STAT3 and telomerase activity in MDA-MB 231 human breast cancer cells

    Directory of Open Access Journals (Sweden)

    Nam-Hoon Kim

    2013-01-01

    Full Text Available Signal transducer and activator of transcription 3 (STAT3 andtelomerase are considered attractive targets for anticancertherapy. The in vitro anticancer activity of the gold(I compoundauranofin was investigated using MDA-MB 231 human breastcancer cells, in which STAT3 is constitutively active. In cellculture, auranofin inhibited growth in a dose-dependent manner,and N-acetyl-L-cysteine (NAC, a scavenger of reactive oxygenspecies (ROS, markedly blocked the effect of auranofin.Incorporation of 5-bromo-2’-deoxyuridine into DNA andanchorage-independent cell growth on soft agar were decreasedby auranofin treatment. STAT3 phosphorylation and telomeraseactivity were also attenuated in cells exposed to auranofin, butNAC pretreatment restored STAT3 phosphorylation andtelomerase activity in these cells. These findings indicate thatauranofin exerts in vitro antitumor effects in MDA-MB 231 cellsand its activity involves inhibition of STAT3 and telomerase.Thus, auranofin shows potential as a novel anticancer drug thattargets STAT3 and telomerase. [BMB Reports 2013; 46(1: 59-64

  7. Mentha arvensis (Linn.-mediated green silver nanoparticles trigger caspase 9-dependent cell death in MCF7 and MDA-MB-231 cells

    Directory of Open Access Journals (Sweden)

    Banerjee PP

    2017-04-01

    Full Text Available Prajna Paramita Banerjee,1 Arindam Bandyopadhyay,1 Singapura Nagesh Harsha,2 Rudragoud S Policegoudra,3 Shelley Bhattacharya,4 Niranjan Karak,2 Ansuman Chattopadhyay1 1Molecular Genetics Laboratory, Department of Zoology, Visva-Bharati, Santiniketan, West Bengal, 2Advanced Polymer and Nanomaterial Laboratory, Department of Chemical Sciences, Center for Polymer Science and Technology, Tezpur University, Napaam, 3Division of Pharmaceutical Technology, Defence Research Laboratory, Tezpur, Assam, 4Environmental Toxicology Laboratory, Department of Zoology, Visva-Bharati, Santiniketan, West Bengal, India Introduction: Leaf extract of Mentha arvensis or mint plant was used as reducing agent for the synthesis of green silver nanoparticles (GSNPs as a cost-effective, eco-friendly process compared to that of chemical synthesis. The existence of nanoparticles was characterized by ultraviolet–visible spectrophotometry, dynamic light scattering, Fourier transform infrared spectroscopy, X-ray diffraction, energy-dispersive X-ray analysis, atomic-force microscopy and transmission electron microscopy analyses, which ascertained the formation of spherical GSNPs with a size range of 3–9 nm. Anticancer activities against breast cancer cell lines (MCF7 and MDA-MB-231 were studied and compared with those of chemically synthesized (sodium borohydride [NaBH4]-mediated silver nanoparticles (CSNPs. Materials and methods: Cell survival of nanoparticle-treated and untreated cells was studied by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT assay. Cell-cycle analyses were carried out using fluorescence-activated cell sorting. Cell morphology was observed by fluorescence microscopy. Expression patterns of PARP1, P53, P21, Bcl2, Bax and cleaved caspase 9 as well as caspase 3 proteins in treated and untreated MCF7 and MDA-MB-231 cells were studied by Western blot method. Results: MTT assay results showed that Mentha arvensis-mediated GSNPs

  8. Effects of shRNA targeted inhibition of Midkine expression on the tumorigenic ability of MDA-MB-231 cells in nude mice%shRNA靶向抑制MK表达对MDA-MB-231细胞裸鼠体内成瘤能力的影响

    Institute of Scientific and Technical Information of China (English)

    韩正杰; 张鹏; 孙卓; 巩玉森; 刘慧; 王庆苓

    2016-01-01

    目的:探讨中期因子(Midkine,MK)基因表达对人乳腺癌MDA-MB-231细胞株裸鼠体内成瘤性的影响。方法将转染pSilencer-3.1-H1-MK(MK KD组)和pSilencer-3.1-H1-NC(NC组)质粒的乳腺癌细胞分别接种于雌性BALB/c裸鼠右侧前肢腋部皮下,然后于接种第7、14、21、28和35天观察测量肿瘤大小。结果与NC组相比,MK KD组裸鼠肿瘤形成时间长,并且肿瘤生长速度慢,瘤体重量轻、体积小(P<0.05)。结论抑制MDA-MB-231乳腺癌细胞MK基因的表达,可以抑制裸鼠体内成瘤能力。%Objective To investigate the effects of Midkine ( MK) expression on the tumorigenic ability of MDA -MB-231 cells in nude mice.Methods Plasmids pSilencer -3.1-H1-MK (Group MK KD) and pSilencer-3.1-H1-NC ( Group NC) were transfected into MDA 231 cells which were then inoculated in the right side of female BALB /c nude mice.The tumor size was measured on Days 7, 14, 21, 28 and 35.Results Compared with Group NC, nude mice in Group MK KD showed longer time to develop tumor , with a slower rate of tumor growth , lower tumor volume and weight (P<0.05).Conclusion The inhibition of MK gene expression in MDA -MB-231 cells can inhibit the growth of tumor in nude mice .

  9. Inhibitory effect of salinomycin on human breast cancer cells MDA-MB-231 proliferation through Hedgehog signaling pathway%盐霉素通过 Hedgehog 信号通路抑制乳腺癌细胞 MDA-MB-231的增殖

    Institute of Scientific and Technical Information of China (English)

    卢颖; 张春影; 李青; 毛俊; 马威; 于晓棠; 侯震寰; 李连宏

    2015-01-01

    目的:探讨盐霉素对Hedgehog信号通路的调控作用及盐霉素抑制乳腺癌细胞MDA-MB-231增殖的作用机制。方法培养人乳腺癌细胞MDA-MB-231,在不同浓度盐霉素及不同作用时间下,采用CCK-8比色法检测盐霉素对MDA-MB-231细胞生长的影响,采用流式细胞术观察经盐霉素作用后细胞周期的改变,采用即时定量PCR和Western blot检测盐霉素处理后Hedgehog通路中靶基因Shh、Smo、Gli1的mRNA和蛋白表达的变化。结果盐霉素可以抑制MDA-MB-231的增殖,0、0.4、0.8和1.6μmol/L 作用48 h后抑制率分别为11.18%、25.88%、50.03%和92.65%。盐霉素能够阻滞MDA-MB-231细胞由 G1期进入 S 期,0、0.8和1.6μmol/L 的 S 期比率分别是25.03%、11.85%和35.21%。盐霉素抑制Shh、Smo以及Gli1的mRNA和蛋白的表达具有剂量依赖性。结论盐霉素可以阻滞MDA-MB-231细胞由G1期进入S期,其机制可能是通过下调Hedgehog通路中相关靶基因的表达进而抑制细胞增殖。%Objective To investigate the inhibitory effect of salinomycin on human breast cancer cells in vitro, and to explore the related molecular mechanism.Methods Human breast cancer MDA-MB-231 cells were treated with salinomycin at different concentrations and at various time points.The effect of salinomycin on MDA-MB-231 cells proliferation was studied by CCK-8 method.The cell cycle status was examined by flow cytometry.RT-PCR and Western blot were used to detect the expression of Shh, Smo and Gli1 in the Hedgehog pathway at mRNA and protein levels.Results Proliferation of MDA-MB-231 cells treated with salinomycin was markedly inhibited in a concentration and time dependent manner.Salinomycin at concentrations of 0,0.4,0.8 and 1.6 μmol/L inhibited the growth at the rates of 11.18%,25.88%, 50.03%, 92.65%, respectively.Salinomycin prevented MDA-MB-231 cells from G1 into S phase.Salinomycin at concentrations of 0,0.8 and 1.6μmol/L resulted in S

  10. miRNA-199 a-5 p通过SP1调节ERK5抑制乳腺癌MDA-MB-231细胞侵袭的机制%miRNA-199 a-5 p inhibit the invasion of MDA-MB-231 cells via regulating ERK5 through SP1

    Institute of Scientific and Technical Information of China (English)

    翟丽敏; 杨硕; 李文通

    2015-01-01

    目的:探讨miR-199a-5p对乳腺癌MDA-MB-231细胞的侵袭影响及其作用机制。方法转染miR-199a-5p mimic至MDA-MB-231细胞,Transwell侵袭实验检测miR-199a-5p对MDA-MB-231细胞侵袭能力的影响。采用细胞免疫荧光、Western blot法检测上皮细胞-间充质转化( epithelial-mesenchymal transition, EMT)分子标志物 E-cadherin、vimentin 的表达。应用Western blot法检测miR-199a-5p mimic及其LNA-siRNA对ERK5、pERK5、EGF、SP1表达的影响。染色体免疫共沉淀( chroma-tin immunoprecipitation, CHIP)技术检测SP1是否与ERK5启动子区结合。结果 miR-199a-5p能抑制MDA-MB-231细胞的侵袭,降低vimentin的表达,增强E-cadherin的表达。同时,miR-199a-5p降低ERK5表达并抑制其磷酸化;EGF、SP1的表达也相应减少。相反,应用LNA-siRNA抑制miR-199a-5p后,ERK5、pERK5、EGF、SP1的表达上调。 CHIP结果显示SP1能与ERK5启动子区结合。结论 miR-199a-5p通过调节EGF、SP1下调ERK5的表达并抑制其磷酸化,进而发挥对乳腺癌MDA-MB-231细胞侵袭的抑制作用。%Purpose To study the effect and mechanism of miR-199a-5p on the invasion of breast cancer MDA-MB-231 cells. Meth-ods miR-199a-5p mimic was transfected into MDA-MB-231 cells. Influence of miR-199a-5p on the invasion of MDA-MB-231 cell was displayed by Transwell, the expression of epithelial-mesenchymal transition ( EMT) molecular markers ( E-cadherin, vimentin) regulated by miR-199a-5p was determined using immunofluorescence and Western blot. Western blot was employed to assess the levels of ERK5, pERK5, EGF and SP1 in MDA-MB-231 cells dealt with miR-199a-5p mimic and LNA-siRNA. Chromatin immunoprecipita-tion (CHIP) was applied for displaying the reaction of SP1 with ERK5 promoter. Results miR-199a-5p could inhibit the invasion of MDA-MB-231 cells, decrease the expression of vimentin and enhance E-cadherin. Meanwhile, miR-199a-5p decreased the expression of ERK5 and pERK5, the levels of EGF and SP1 were

  11. Ziyuglycoside I Inhibits the Proliferation of MDA-MB-231 Breast Carcinoma Cells through Inducing p53-Mediated G2/M Cell Cycle Arrest and Intrinsic/Extrinsic Apoptosis

    Science.gov (United States)

    Zhu, Xue; Wang, Ke; Zhang, Kai; Zhang, Ting; Yin, Yongxiang; Xu, Fei

    2016-01-01

    Background: Due to the aggressive clinical behavior, poor outcome, and lack of effective specific targeted therapies, triple-negative breast cancer (TNBC) has currently been recognized as one of the most malignant types of tumors. In the present study, we investigated the cytotoxic effect of ziyuglycoside I, one of the major components extracted from Chinese anti-tumor herbal Radix Sanguisorbae, on the TNBC cell line MDA-MB-231. Methods: The underlying molecular mechanism of the cytotoxic effect ziyuglycoside I on MDA-MB-231 cells was investigated with cell viability assay, flow cytometric analysis and Western blot. Results: Compared to normal mammary gland Hs 578Bst cells, treatment of ziyuglycoside I resulted in a significant growth inhibitory effect on MDA-MB-231 cells. Ziyuglycoside I induced the G2/M phase arrest and apoptosis of MDA-MB-231 cells in a dose-dependent manner. These effects were found to be partially mediated through the up-regulation of p53 and p21WAF1, elevated Bax/Bcl-2 ratio, and the activation of both intrinsic (mitochondrial-initiated) and extrinsic (Fas/FasL-initiated) apoptotic pathways. Furthermore, the p53 specific siRNA attenuated these effects. Conclusion: Our study suggested that ziyuglycoside I-triggered MDA-MB-231 cell cycle arrest and apoptosis were probably mediated by p53. This suggests that ziyuglycoside I might be a potential drug candidate for treating TNBC. PMID:27879682

  12. Ziyuglycoside I Inhibits the Proliferation of MDA-MB-231 Breast Carcinoma Cells through Inducing p53-Mediated G2/M Cell Cycle Arrest and Intrinsic/Extrinsic Apoptosis.

    Science.gov (United States)

    Zhu, Xue; Wang, Ke; Zhang, Kai; Zhang, Ting; Yin, Yongxiang; Xu, Fei

    2016-11-22

    Due to the aggressive clinical behavior, poor outcome, and lack of effective specific targeted therapies, triple-negative breast cancer (TNBC) has currently been recognized as one of the most malignant types of tumors. In the present study, we investigated the cytotoxic effect of ziyuglycoside I, one of the major components extracted from Chinese anti-tumor herbal Radix Sanguisorbae, on the TNBC cell line MDA-MB-231. The underlying molecular mechanism of the cytotoxic effect ziyuglycoside I on MDA-MB-231 cells was investigated with cell viability assay, flow cytometric analysis and Western blot. Compared to normal mammary gland Hs 578Bst cells, treatment of ziyuglycoside I resulted in a significant growth inhibitory effect on MDA-MB-231 cells. Ziyuglycoside I induced the G2/M phase arrest and apoptosis of MDA-MB-231 cells in a dose-dependent manner. These effects were found to be partially mediated through the up-regulation of p53 and p21(WAF1), elevated Bax/Bcl-2 ratio, and the activation of both intrinsic (mitochondrial-initiated) and extrinsic (Fas/FasL-initiated) apoptotic pathways. Furthermore, the p53 specific siRNA attenuated these effects. Our study suggested that ziyuglycoside I-triggered MDA-MB-231 cell cycle arrest and apoptosis were probably mediated by p53. This suggests that ziyuglycoside I might be a potential drug candidate for treating TNBC.

  13. Ziyuglycoside I Inhibits the Proliferation of MDA-MB-231 Breast Carcinoma Cells through Inducing p53-Mediated G2/M Cell Cycle Arrest and Intrinsic/Extrinsic Apoptosis

    Directory of Open Access Journals (Sweden)

    Xue Zhu

    2016-11-01

    Full Text Available Background: Due to the aggressive clinical behavior, poor outcome, and lack of effective specific targeted therapies, triple-negative breast cancer (TNBC has currently been recognized as one of the most malignant types of tumors. In the present study, we investigated the cytotoxic effect of ziyuglycoside I, one of the major components extracted from Chinese anti-tumor herbal Radix Sanguisorbae, on the TNBC cell line MDA-MB-231. Methods: The underlying molecular mechanism of the cytotoxic effect ziyuglycoside I on MDA-MB-231 cells was investigated with cell viability assay, flow cytometric analysis and Western blot. Results: Compared to normal mammary gland Hs 578Bst cells, treatment of ziyuglycoside I resulted in a significant growth inhibitory effect on MDA-MB-231 cells. Ziyuglycoside I induced the G2/M phase arrest and apoptosis of MDA-MB-231 cells in a dose-dependent manner. These effects were found to be partially mediated through the up-regulation of p53 and p21WAF1, elevated Bax/Bcl-2 ratio, and the activation of both intrinsic (mitochondrial-initiated and extrinsic (Fas/FasL-initiated apoptotic pathways. Furthermore, the p53 specific siRNA attenuated these effects. Conclusion: Our study suggested that ziyuglycoside I-triggered MDA-MB-231 cell cycle arrest and apoptosis were probably mediated by p53. This suggests that ziyuglycoside I might be a potential drug candidate for treating TNBC.

  14. Effect of Recombinant Human Erythropoietin on Proliferation of Breast Cancer MDA-MB-231 Cells and Its Mechanism%重组人促红细胞生成素对人乳腺癌MDA-MB-231细胞增殖的影响及其作用机制研究

    Institute of Scientific and Technical Information of China (English)

    晋雯; 孔令英; 张小容; 杨丽

    2013-01-01

    目的 探讨重组人促红细胞生成素(recombinant human erythropoietin,rh-EPO)对人乳腺癌MDA-MB-231细胞增殖的影响及其作用机制.方法 将人乳腺癌 MDA-MB-231 细胞进行培养.传至5~6代,细胞生长状态稳定后,收集人乳腺癌 MDA-MB-231细胞用于MTT实验.采用MTT法检测 5 组(阴性对照组、rh-EPO A 组、rh-EPO B组、rh-EPO C 组和rh-EPO D 组)MDA-MB-231细胞增殖的情况.用10 μmol·L-1p38MAPK抑制剂SB203580、ERK抑制剂U0126、JNK抑制剂SP600125和NF-κB 抑制剂PDTC预处理人乳腺癌 MDA-MB-231 细胞后,用MTT法检测经100、200、300和400 U·mL-1的rh-EPO(PDTC+EPO 组、SB203580+EPO 组、SP600125+EPO组和U0126+EPO组)诱导后细胞增殖的情况.结果 阴性对照组、rh-EPO A 组、rh-EPO B组、rh-EPO C 组和rh-EPO D 组 72 h PI值分别为:1.000 0±1.000 0、1.231 8±0.133 0、1.323 9±0.136 0、1.351 7±0.146 0和1.423 1±0.084 0;96 h PI值分别为:1.000 0±1.000 0、1.352 5±0.036 0、1.359 7±0.112 0、1.387 2±0.063 0和1.410 8±0.060 0.rh-EPO A 组、rh-EPO B组、rh-EPO C 组和rh-EPO D 组 72、96 h PI值与阴性对照组比较差异均有统计学意义(均P<0.05).PDTC+EPO 组、SB203580+EPO 组72、96 h PI值均较EPO组明显降低(均P<0.05),SP600125+EPO组、U0126+EPO组72、96 h PI值与EPO组比较差异均无统计学意义(均P>0.05).结论 rh-EPO可能是通过NF-κB、MAPK传导通路发挥效应,促进人乳腺癌MDA-MB-231细胞增殖.

  15. Cytotoxic activity of ten algae from the Persian Gulf and Oman Sea on human breast cancer cell lines; MDA-MB-231, MCF-7, and T-47D

    Directory of Open Access Journals (Sweden)

    Nasrollah Erfani

    2015-01-01

    Full Text Available Background: Seaweeds have proven to be a promising natural source of bioactive metabolites for drug development. Objective: This study aimed to monitor the ethanol extract of ten algae from the Persian Gulf and Oman Sea, for their in vitro cytotoxic activity on three human breast cancer cell lines. Materials and Methods: Three human breast cancer cell lines including MDA-MB-231(ER− , MCF-7(ER + , and T-47D (ER + were treated by different concentrations of total ethanol (90% algae extracts and the cytotoxic effects were evaluated by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay. Doxorubicin (Ebewe, Austria was used as a positive control. After 72 h of incubation, the cytotoxic effect of the algae was calculated and presented as 50%-inhibitory concentration (IC 50 . Results: The results indicated Gracilaria foliifera and Cladophoropsis sp. to be the most active algae in terms of cytotoxic effects on the investigated cancer cell lines. The IC 50 values against MDA-MB-231, MCF-7, and T-47D cells were, respectively, 74.89 ± 21.71, 207.81 ± 12.07, and 203.25 ± 30.98 mg/ml for G. foliifera and 66.48 ± 4.96, 150.86 ± 51.56 and >400 mg/ml for Cladophoropsis sp. The rest of the algal extracts were observed not to have significant cytotoxic effects in the concentration range from 6.25 mg/ml to 400 mg/ml. Conclusion: Our data conclusively suggest that G. foliifera and Cladophoropsis sp. may be good candidates for further fractionation to obtain novel anticancer substances. Moreover, stronger cytotoxic effects on estrogen negative breast cancer cell line (MDA-MB-231(ER− in comparison to estrogen positive cells (MCF-7 and T-47D suggest that the extract of G. foliifera and Cladophoropsis sp. may have an estrogen receptor/progesterone receptor-independent mechanism for their cellular growth inhibition.

  16. Stromelysin-3 over-expression enhances tumourigenesis in MCF-7 and MDA-MB-231 breast cancer cell lines: involvement of the IGF-1 signalling pathway

    Directory of Open Access Journals (Sweden)

    Mennerich Detlev

    2007-01-01

    Full Text Available Abstract Background Stromelysin-3 (ST-3 is over-expressed in the majority of human carcinomas including breast carcinoma. Due to its known effect in promoting tumour formation, but its impeding effect on metastasis, a dual role of ST-3 in tumour progression, depending on the cellular grade of dedifferentiation, was hypothesized. Methods The present study was designed to investigate the influence of ST-3 in vivo and in vitro on the oestrogen-dependent, non-invasive MCF-7 breast carcinoma cell line as well as on the oestrogen-independent, invasive MDA-MB-231 breast carcinoma cell line. Therefore an orthotopic human xenograft tumour model in nude mice, as well as a 3D matrigel cell culture system, were employed. Results Using both in vitro and in vivo techniques, we have demonstrated that over-expression of ST-3 in MCF-7 and MDA-MB-231 cells leads to both increased cell numbers and tumour volumes. This observation was dependent upon the presence of growth factors. In particular, the enhanced proliferative capacity was in MCF-7/ST-3 completely and in MDA-MB-231/ST-3 cells partially dependent on the IGF-1 signalling pathway. Microarray analysis of ST-3 over-expressing cells revealed that in addition to cell proliferation, further biological processes seemed to be affected, such as cell motility and stress response. The MAPK-pathway as well as the Wnt and PI3-kinase pathways, appear to also play a potential role. Furthermore, we have demonstrated that breast cancer cell lines of different differentiation status, as well as the non-tumourigenic cell line MCF-10A, have a comparable capability to induce endogenous ST-3 expression in fibroblasts. Conclusion These data reveal that ST-3 is capable of enhancing tumourigenesis in highly differentiated "early stage" breast cancer cell lines as well as in further progressed breast cancer cell lines that have already undergone epithelial-mesenchymal transition. We propose that ST-3 induction in tumour

  17. Cochinchina momordica seed extract induces G2/M arrest and apoptosis in human breast cancer MDA-MB-231 cells by modulating the PI3K/Akt pathway.

    Science.gov (United States)

    Meng, Lin-Yi; Liu, Hong-Rui; Shen, Yang; Yu, Yun-Qiu; Tao, Xia

    2011-01-01

    Cochinchina momordica seeds are a kind of traditional Chinese herb. In this study, anticancer activity and underlying mechanisms were investigated with an extract using human breast cancer MDA-MB-231 cells. The survival rate was reduced in a concentration- and time-dependent manner as assessed by MTT assay. After incubation for 48 h, typical apoptotic morphological changes were observed by Hoechst 33258 dye assay. Flow cytometry revealed that the treatment obviously induced G2/M arrest and apoptosis in MDA-MB-231 cells. Furthermore, western blotting demonstrated downregulation of protein expression of PI3K, Akt, NF-kB, Bcl-2, Cdk1 and cyclin B1, whereas Bax and caspase-3 were upregulated. Our results suggest that the extract induced cell cycle G2/M arrest and apoptosis in MDA-MB-231 cells by decreasing PI3K/Akt pathway. Therefore, we propose that ECMS has potential as a breast cancer chemotherapeutic agent.

  18. Phaleria macrocarpa (Boerl.) fruit induce G0/G1 and G2/M cell cycle arrest and apoptosis through mitochondria-mediated pathway in MDA-MB-231 human breast cancer cell.

    Science.gov (United States)

    Kavitha, Nowroji; Ein Oon, Chern; Chen, Yeng; Kanwar, Jagat R; Sasidharan, Sreenivasan

    2017-04-06

    Phaleria macrocarpa (Scheff) Boerl, is a well-known folk medicinal plant in Indonesia. Traditionally, P. macrocarpa has been used to control cancer, impotency, hemorrhoids, diabetes mellitus, allergies, liver and hearth disease, kidney disorders, blood diseases, acne, stroke, migraine, and various skin diseases. The purpose of this study was to determine the in situ cytotoxicity effect P. macrocarpa fruit ethyl acetate fraction (PMEAF) and the underlying molecular mechanism of cell death. MDA-MB-231 cells were incubated with PMEAF for 24h. Cell cycle and viability were examined using flow cytometry analysis. Apoptosis was determined using the Annexin V assay and also by fluorescence microscopy. Apoptosis protein profiling was detected by RayBio® Human Apoptosis Array. The AO/PI staining and flow cytometric analysis of MDA-MB-231 cells treated with PMEAF were showed apoptotic cell death. The cell cycle analysis by flow cytometry analysis revealed that the accumulation of PMEAF treated MDA-MB-231 cells in G0/G1 and G2/M-phase of the cell cycle. Moreover, the PMEAF exert cytotoxicity by increased the ROS production in MDA-MB-231 cells consistently stimulated the loss of mitochondrial membrane potential (∆Ψm) and induced apoptosis cell death by activation of numerous signalling proteins. The results from apoptosis protein profiling array evidenced that PMEAF stimulated the expression of 9 pro-apoptotic proteins (Bax, Bid, caspase 3, caspase 8, cytochrome c, p21, p27, p53 and SMAC) and suppressed the 4 anti-apoptotic proteins (Bcl-2, Bcl-w, XIAP and survivin) in MDA-MB-231 cells. The results indicated that PMEAF treatment induced apoptosis in MDA-MB-231 cells through intrinsic mitochondrial related pathway with the participation of pro and anti-apoptotic proteins, caspases, G0/G1 and G2/M-phases cell cycle arrest by p53-mediated mechanism. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  19. Synthesis and Single Crystal X-Ray Structure of New (2E-2-[3-(1H-Imidazol-1-yl-1-phenylpropylidene]-N-phenylhydrazinecarboxamide

    Directory of Open Access Journals (Sweden)

    Mohamed I. Attia

    2013-01-01

    Full Text Available Synthesis, spectroscopic characterization and X-ray crystal structure of a new (2E-2-[3-(1H-imidazol-1-yl-1-phenylpropylidene]-N-phenylhydrazinecarboxamide (4 are reported. The stereochemistry of the title compound 4, C19H19N5O, about the imine bond [1.296 (4 Å] was assigned to have (E-configuration. In the urea moiety, the N–H entities are trans to each other, and one of these forms is an intramolecular N–H⋯H hydrogen bond. The compound crystallizes in the monoclinic space group P21/c with a = 5.8093 (2 Å, b = 20.5575 (6 Å, c = 14.0355 (5 Å, α = 90.00°, β = 97.365° (2, γ = 90.00°, V = 1662.36 (10 Å3, and Z = 4. The molecules are packed in crystal structure by weak intermolecular hydrogen interactions.

  20. Changes in cell migration due to the combined effects of sonodynamic therapy and photodynamic therapy on MDA-MB-231 cells

    Science.gov (United States)

    Wang, Haiping; Wang, Pan; Zhang, Kun; Wang, Xiaobing; Liu, Quanhong

    2015-03-01

    Sono-photodynamic therapy is an emerging method with an increasing amount of research having demonstrated its anti-cancer efficacy. However, the impacts of cell migration ability after sono-photodynamic therapy have seldom been reported. In this study, we identified cell migration by wound healing and transwell assays. Significant inability of cell migration was observed in combined groups accompanied by the decline of cell adhesion. Cells in combined treatment groups showed serious microfilament network collapse as well as decreased expression of matrix metalloproteinases-9. These results suggested that sono-photodynamic therapy could inhibit MDA-MB-231 cell migration and that the microfilament and matrix metalloproteinases-9 disorder might be involved.

  1. pACC1 peptide loaded chitosan nanoparticles induces apoptosis via reduced fatty acid synthesis in MDA-MB-231 cells

    Science.gov (United States)

    Kaliaperumal, Jagatheesh; Hari, Natarajan; Pavankumar, Padarthi; Elangovan, Namasivayam

    2016-06-01

    The development of formulations with therapeutic peptides has been restricted to poor cell penetration and in this attempt; we developed pACC1 peptide loaded chitosan nanoparticles. The prepared nanoparticles were characterized with FT-IR, XRD, SEM and TEM. In addition, the suitable formulation was evaluated for hemocompatibility, plasma stability and embryo toxicity using Danio rerio embryo model. The results showed that pACC1 peptide loaded chitosan nanoparticles were compatible with plasma. They possess sustained release pattern and also found to be safe up to 300 mg/L in embryo toxicity tests. Cytotoxicity assays with MDA-MB-231 cell lines suggested that, pACC1 peptide loaded chitosan nanoparticles were capable of enhanced cellular penetration and reduced palmitic acid content, which was confirmed by H1 NMR. Hence, these nanoparticles could be employed as excellent adjuvant therapeutics while treating solid tumors with multi-drug resistance.

  2. Transmembrane protein 85 from both human (TMEM85) and yeast (YGL231c) inhibit hydrogen peroxide mediated cell death in yeast.

    Science.gov (United States)

    Ring, Giselle; Khoury, Chamel M; Solar, Aidan J; Yang, Zhao; Mandato, Craig A; Greenwood, Michael T

    2008-07-23

    Anti-apoptotic proteins are involved in modulating the process of apoptosis. Here, we report the identification of the previously uncharacterized transmembrane domain protein 85 (TMEM85) as a novel anti-apoptotic sequence. Using growth and viability assays, we demonstrate that the heterologous expression of human TMEM85 in yeast promotes growth and prevents cell death in response to oxidative stress. Overexpression of the yeast TMEM85 ortholog (YGL231c) also leads to increased resistance to oxidative stress. Analysis of the existing TMEM85 DNA complimentary to mRNAs revealed that the human TMEM85 gene is alternatively spliced to produce multiple transcripts and proteins. Thus TMEM85 is a complex gene that encodes a novel conserved anti-apoptotic protein.

  3. Environmental Performance Report 2013: Annual Site Environmental Report per the U.S. Department of Energy Order 231.1-1B (Management Publication)

    Energy Technology Data Exchange (ETDEWEB)

    Schlomberg, K.; Eickhoff, J.; Beatty, B.; Braus, G.; Durbin, L.; Fiehweg, R.; Ray, M.; Ryon, T.; Schmitz, E.

    2014-08-01

    The National Renewable Energy Laboratory's (NREL's) Environmental Performance Report provides a description of the laboratory's environmental management activities for 2013, including information on environmental and sustainability performance, environmental compliance activities and status, and environmental protection programs, highlights, and successes. The purpose of this report is to ensure that U.S. Department of Energy (DOE) and the public receive timely, accurate information about events that have affected or could adversely affect the health, safety, and security of the public or workers; the environment; or the operations of DOE facilities. This report meets the requirements of the Annual Site Environmental Report and is prepared in accordance with the DOE Order 231.1B, Environment, Safety and Health Reporting.

  4. Tissue factor-factor VIIa-specific up-regulation of IL-8 expression in MDA-MB-231 cells is mediated by PAR-2 and results in increased cell migration

    DEFF Research Database (Denmark)

    Hjortoe, Gertrud M; Petersen, Lars C; Albrektsen, Tatjana

    2004-01-01

    in these processes. To elucidate the potential mechanisms by which TF contributes to tumor invasion and metastasis, we investigated the effect of FVIIa on IL-8 expression and cell migration in a breast carcinoma cell line, MDA-MB-231, a cell line that constitutively expresses abundant TF. Expression of IL-8 m......RNA in MDA-MB-231 cells was markedly up-regulated by plasma concentrations of FVII or an equivalent concentration of FVIIa (10 nM). Neither thrombin nor other proteases involved in hemostasis were effective in stimulating IL-8 in these cells. Increased transcriptional activation of the IL-8 gene...

  5. 4-氨基-2-三氟甲基苯基维甲酸酯对人乳腺癌细胞株MDA-MB-231诱导分化作用及可能的机制研究%Inducing effect of 4-Amino-2-Trifluoromethyl-Phenyl Retinate on differentiation of human breast cancer MDA-MB-231 cell and its possible mechanisms

    Institute of Scientific and Technical Information of China (English)

    雷静; 陈飞虎; 葛金芳; 李悦; 高文凡; 邓子云

    2015-01-01

    目的:观察4-氨基-2-三氟甲基苯基维甲酸酯(4-anino-2-trifluoromethyl-phenyl retimate, ATPR)对人乳腺癌细胞株MDA-MB-231抑制增殖诱导分化作用,探讨其可能的作用机制。方法体外培养人乳腺癌细胞株 MDA-MB-231, MTT检测细胞增殖,绘制细胞生长曲线,瑞氏-吉姆萨染色观察细胞形态变化,酶联免疫法检测粘蛋白MUC-1活性,流式细胞术检测细胞周期,实时荧光定量PCR法和Western blot法检测维甲酸受体(retinoic acid receptors,RAR) RARα、RARβ、RARγ和维甲类受体( retinoid X receptors, RXR ) RXRα、RXRβ、RXRγ基因和蛋白的表达。结果 ATPR 能够抑制MDA-MB-231细胞的增殖,具有浓度-时间依赖性,染色后镜下观察 MDA-MB-231细胞生长密度降低,形态趋于正常。ELISA结果显示,ATPR作用后明显降低MDA-MB-231细胞培养上清中MUC-1的浓度;流式细胞术结果显示,MDA-MB-231细胞中G0/G1期表达量增加,S期表达量减少,细胞阻滞在G0/G1期比例增加。 q-RT-PCR和Western blot结果显示, ATPR作用后, RARγ的mRNA和蛋白表达水平降低, RXRs mRNA和蛋白水平无明显变化。结论 ATPR可以抑制人乳腺癌细胞株MDA-MB-231增殖并诱导其分化,其机制可能与RARγ的表达有关。%Aim To investigate the effect of 4-Amino- 2-Trifluoromethyl-Phenyl Retinate on human breast cancer cells MDA-MB-231 and the possible mecha-nisms. Method Human breast cancer MDA-MB-231 cells were incubated with different concentrations of ATPR in vitro. MTT assay was performed to measure the proliferation of MDA-MB-231 . Cell growth curves were made by counting cells and morphologic changes were observed by Wright-Giemsa staining. The differ-entiation marker mucin-1 ( MUC-1 ) was measured by enzyme linked immunosorbent assay ( ELISA ) . Cell cycle was examined by Flow cytometry ( FCM ) . The expression of retinoic acid receptors ( RARs) and reti-noid X receptors ( RXRs ) were detected by Western blot and Quantitative

  6. Glycerol-3-phosphate acyltranferase-2 behaves as a cancer testis gene and promotes growth and tumorigenicity of the breast cancer MDA-MB-231 cell line.

    Directory of Open Access Journals (Sweden)

    Magali Pellon-Maison

    Full Text Available The de novo synthesis of glycerolipids in mammalian cells begins with the acylation of glycerol-3-phosphate, catalyzed by glycerol-3-phosphate acyltransferase (GPAT. GPAT2 is a mitochondrial isoform primarily expressed in testis under physiological conditions. Because it is aberrantly expressed in multiple myeloma, it has been proposed as a novel cancer testis gene. Using a bioinformatics approach, we found that GPAT2 is highly expressed in melanoma, lung, prostate and breast cancer, and we validated GPAT2 expression at the protein level in breast cancer by immunohistochemistry. In this case GPAT2 expression correlated with a higher histological grade. 5-Aza-2' deoxycytidine treatment of human cells lines induced GPAT2 expression suggesting epigenetic regulation of gene expression. In order to evaluate the contribution of GPAT2 to the tumor phenotype, we silenced its expression in MDA-MB-231 cells. GPAT2 knockdown diminished cell proliferation, anchorage independent growth, migration and tumorigenicity, and increased staurosporine-induced apoptosis. In contrast, GPAT2 over-expression increased cell proliferation rate and resistance to staurosporine-induced apoptosis. To understand the functional role of GPAT2, we performed a co-expression analysis in mouse and human testis and found a significant association with semantic terms involved in cell cycle, DNA integrity maintenance, piRNA biogenesis and epigenetic regulation. Overall, these results indicate the GPAT2 would be directly associated with the control of cell proliferation. In conclusion, we confirm GPAT2 as a cancer testis gene and that its expression contributes to the tumor phenotype of MDA-MB-231 cells.

  7. Structural analysis of DNA binding by C.Csp231I, a member of a novel class of R-M controller proteins regulating gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Shevtsov, M. B.; Streeter, S. D.; Thresh, S.-J.; Swiderska, A.; McGeehan, J. E.; Kneale, G. G., E-mail: geoff.kneale@port.ac.uk [University of Portsmouth, Portsmouth PO1 2DY (United Kingdom)

    2015-02-01

    The structure of the new class of controller proteins (exemplified by C.Csp231I) in complex with its 21 bp DNA-recognition sequence is presented, and the molecular basis of sequence recognition in this class of proteins is discussed. An unusual extended spacer between the dimer binding sites suggests a novel interaction between the two C-protein dimers. In a wide variety of bacterial restriction–modification systems, a regulatory ‘controller’ protein (or C-protein) is required for effective transcription of its own gene and for transcription of the endonuclease gene found on the same operon. We have recently turned our attention to a new class of controller proteins (exemplified by C.Csp231I) that have quite novel features, including a much larger DNA-binding site with an 18 bp (∼60 Å) spacer between the two palindromic DNA-binding sequences and a very different recognition sequence from the canonical GACT/AGTC. Using X-ray crystallography, the structure of the protein in complex with its 21 bp DNA-recognition sequence was solved to 1.8 Å resolution, and the molecular basis of sequence recognition in this class of proteins was elucidated. An unusual aspect of the promoter sequence is the extended spacer between the dimer binding sites, suggesting a novel interaction between the two C-protein dimers when bound to both recognition sites correctly spaced on the DNA. A U-bend model is proposed for this tetrameric complex, based on the results of gel-mobility assays, hydrodynamic analysis and the observation of key contacts at the interface between dimers in the crystal.

  8. Activation of H-Ras and Rac1 correlates with epidermal growth factor-induced invasion in Hs578T and MDA-MB-231 breast carcinoma cells.

    Science.gov (United States)

    Koh, Min-Soo; Moon, Aree

    2011-03-01

    There is considerable experimental evidence that hyperactive Ras proteins promote breast cancer growth and development including invasiveness, despite the low frequency of mutated forms of Ras in breast cancer. We have previously shown that H-Ras, but not N-Ras, induces an invasive phenotype mediated by small GTPase Rac1 in MCF10A human breast epithelial cells. Epidermal growth factor (EGF) plays an important role in aberrant growth and metastasis formation of many tumor types including breast cancer. The present study aims to investigate the correlation between EGF-induced invasiveness and Ras activation in four widely used breast cancer cell lines. Upon EGF stimulation, invasive abilities and H-Ras activation were significantly increased in Hs578T and MDA-MB-231 cell lines, but not in MDA-MB-453 and T47D cell lines. Using small interfering RNA (siRNA) to target H-Ras, we showed a crucial role of H-Ras in the invasive phenotype induced by EGF in Hs578T and MDA-MB-231 cells. Moreover, siRNA-knockdown of Rac1 significantly inhibited the EGF-induced invasiveness in these cells. Taken together, this study characterized human breast cancer cell lines with regard to the relationship between H-Ras activation and the invasive phenotype induced by EGF. Our data demonstrate that the activation of H-Ras and the downstream molecule Rac1 correlates with EGF-induced breast cancer cell invasion, providing important information on the regulation of malignant progression in mammary carcinoma cells.

  9. The Complete Ultraviolet Spectrum of the Archetypal "Wind-dominated" Quasar Mrk 231: Absorption and Emission from a High-speed Dusty Nuclear Outflow

    Science.gov (United States)

    Veilleux, S.; Meléndez, M.; Tripp, T. M.; Hamann, F.; Rupke, D. S. N.

    2016-07-01

    New near- and far-ultraviolet (NUV and FUV) Hubble Space Telescope spectra of Mrk 231, the nearest quasar known, are combined with ground-based optical spectra to study the remarkable dichotomy between the FUV and NUV-optical spectral regions in this object. The FUV emission-line features are faint, broad, and highly blueshifted (up to ˜7000 km s-1), with no significant accompanying absorption. In contrast, the profiles of the NUV absorption features resemble those of the optical Na i D, He i, and Ca ii H and K lines, exhibiting broad blueshifted troughs that overlap in velocity space with the FUV emission-line features and indicate a dusty, high-density and patchy broad absorption line (BAL) screen covering ˜90% of the observed continuum source at a distance ≲2-20 pc. The FUV continuum emission does not show the presence of any obvious stellar features and is remarkably flat compared with the steeply declining NUV continuum. The NUV (FUV) features and continuum emission have not varied significantly over the past ˜22 (3) years and are unresolved on scales ˜40 (170) pc. These results favor an active galactic nucleus origin for the NUV-FUV line and continuum emission. The observed FUV line emission is produced in the outflowing BAL cloud system, while the Balmer lines arise primarily from the standard broad line region seen through the dusty BAL screen. Our data are inconsistent with the recently proposed binary black hole model. We argue instead that Mrk 231 is the nearest example of weak-lined “wind-dominated” quasars with high Eddington ratios and geometrically thick (“slim”) accretion disks; these quasars are likely more common in the early universe.

  10. Oleanolic acid induces migration in Mv1Lu and MDA-MB-231 epithelial cells involving EGF receptor and MAP kinases activation

    Science.gov (United States)

    Ruzafa-Martínez, María; Ramos-Morcillo, Antonio Jesús

    2017-01-01

    During wound healing, skin function is restored by the action of several cell types that undergo differentiation, migration, proliferation and/or apoptosis. These dynamics are tightly regulated by the evolution of the extra cellular matrix (ECM) contents along the process. Pharmacologically active flavonoids have shown to exhibit useful physiological properties interesting in pathological states. Among them, oleanolic acid (OA), a pentacyclic triterpene, shows promising properties over wound healing, as increased cell migration in vitro and improved wound resolution in vivo. In this paper, we pursued to disclose the molecular mechanisms underlying those effects, by using an in vitro scratch assay in two epithelial cell lines of different linage: non-malignant mink lung epithelial cells, Mv1Lu; and human breast cancer cells, MDA-MB-231. In every case, we observed that OA clearly enhanced cell migration for in vitro scratch closure. This correlated with the stimulation of molecular pathways related to mitogen-activated protein (MAP) kinases, as ERK1,2 and Jun N-terminal kinase (JNK) 1,2 activation and c-Jun phosphorylation. Moreover, MDA-MB-231 cells treated with OA displayed an altered gene expression profile affecting transcription factor genes (c-JUN) as well as proteins involved in migration and ECM dynamics (PAI1), in line with the development of an epithelial to mesenchymal transition (EMT) status. Strikingly, upon OA treatment, we observed changes in the epidermal growth factor receptor (EGFR) subcellular localization, while interfering with its signalling completely prevented migration effects. This data provides a physiological framework supporting the notion that lipophilic plant extracts used in traditional medicine, might modulate wound healing processes in vivo through its OA contents. The molecular implications of these observations are discussed. PMID:28231262

  11. Gallic acid indanone and mangiferin xanthone are strong determinants of immunosuppressive anti-tumour effects of Mangifera indica L. bark in MDA-MB231 breast cancer cells.

    Science.gov (United States)

    García-Rivera, Dagmar; Delgado, René; Bougarne, Nadia; Haegeman, Guy; Berghe, Wim Vanden

    2011-06-01

    Vimang is a standardized extract derived from Mango bark (Mangifera Indica L.), commonly used as anti-inflammatory phytomedicine, which has recently been used to complement cancer therapies in cancer patients. We have further investigated potential anti-tumour effects of glucosylxanthone mangiferin and indanone gallic acid, which are both present in Vimang extract. We observed significant anti-tumour effects of both Vimang constituents in the highly aggressive and metastatic breast cancer cell type MDA-MB231. At the molecular level, mangiferin and gallic acid both inhibit classical NFκB activation by IKKα/β kinases, which results in impaired IκB degradation, NFκB translocation and NFκB/DNA binding. In contrast to the xanthone mangiferin, gallic acid further inhibits additional NFκB pathways involved in cancer cell survival and therapy resistance, such as MEK1, JNK1/2, MSK1, and p90RSK. This results in combinatorial inhibition of NFκB activity by gallic acid, which results in potent inhibition of NFκB target genes involved in inflammation, metastasis, anti-apoptosis and angiogenesis, such as IL-6, IL-8, COX2, CXCR4, XIAP, bcl2, VEGF. The cumulative NFκB inhibition by gallic acid, but not mangiferin, is also reflected at the level of cell survival, which reveals significant tumour cytotoxic effects in MDA-MB231 cells. Altogether, we identify gallic acid, besides mangiferin, as an essential anti-cancer component in Vimang extract, which demonstrates multifocal inhibition of NFκB activity in the cancer-inflammation network.

  12. Polymorphic segmental duplications at 8p23.1 challenge the determination of individual defensin gene repertoires and the assembly of a contiguous human reference sequence

    Directory of Open Access Journals (Sweden)

    Loncarevic Ivan F

    2004-12-01

    Full Text Available Abstract Background Defensins are important components of innate immunity to combat bacterial and viral infections, and can even elicit antitumor responses. Clusters of defensin (DEF genes are located in a 2 Mb range of the human chromosome 8p23.1. This DEF locus, however, represents one of the regions in the euchromatic part of the final human genome sequence which contains segmental duplications, and recalcitrant gaps indicating high structural dynamics. Results We find that inter- and intraindividual genetic variations within this locus prevent a correct automatic assembly of the human reference genome (NCBI Build 34 which currently even contains misassemblies. Manual clone-by-clone alignment and gene annotation as well as repeat and SNP/haplotype analyses result in an alternative alignment significantly improving the DEF locus representation. Our assembly better reflects the experimentally verified variability of DEF gene and DEF cluster copy numbers. It contains an additional DEF cluster which we propose to reside between two already known clusters. Furthermore, manual annotation revealed a novel DEF gene and several pseudogenes expanding the hitherto known DEF repertoire. Analyses of BAC and working draft sequences of the chimpanzee indicates that its DEF region is also complex as in humans and DEF genes and a cluster are multiplied. Comparative analysis of human and chimpanzee DEF genes identified differences affecting the protein structure. Whether this might contribute to differences in disease susceptibility between man and ape remains to be solved. For the determination of individual DEF gene repertoires we provide a molecular approach based on DEF haplotypes. Conclusions Complexity and variability seem to be essential genomic features of the human DEF locus at 8p23.1 and provides an ongoing challenge for the best possible representation in the human reference sequence. Dissection of paralogous sequence variations, duplicon SNPs ans

  13. Proteomic and bioinformatic analyses of possible target-related proteins of gambogic acid in human breast carcinoma MDA-MB-231 cells.

    Science.gov (United States)

    Li, Dong; Song, Xiao-Yi; Yue, Qing-Xi; Cui, Ya-Jun; Liu, Miao; Feng, Li-Xing; Wu, Wan-Ying; Jiang, Bao-Hong; Yang, Min; Qu, Xiao-Bo; Liu, Xuan; Guo, De-An

    2015-01-01

    Gambogic acid (GA) is an anticancer agent in phase ‖b clinical trial in China but its mechanism of action has not been fully clarified. The present study was designed to search the possible target-related proteins of GA in cancer cells using proteomic method and establish possible network using bioinformatic analysis. Cytotoxicity and anti-migration effects of GA in MDA-MB-231 cells were checked using MTT assay, flow cytometry, wound migration assay, and chamber migration assay. Possible target-related proteins of GA at early (3 h) and late stage (24 h) of treatment were searched using a proteomic technology, two-dimensional electrophoresis (2-DE). The possible network of GA was established using bioinformatic analysis. The intracellular expression levels of vimentin, keratin 18, and calumenin were determined using Western blotting. GA inhibited cell proliferation and induced cell cycle arrest at G2/M phase and apoptosis in MDA-MB-231 cells. Additionally, GA exhibited anti-migration effects at non-toxic doses. In 2-DE analysis, totally 23 possible GA targeted proteins were found, including those with functions in cytoskeleton and transport, regulation of redox state, metabolism, ubiquitin-proteasome system, transcription and translation, protein transport and modification, and cytokine. Network analysis of these proteins suggested that cytoskeleton-related proteins might play important roles in the effects of GA. Results of Western blotting confirmed the cleavage of vimentin, increase in keratin 18, and decrease in calumenin levels in GA-treated cells. In summary, GA is a multi-target compound and its anti-cancer effects may be based on several target-related proteins such as cytoskeleton-related proteins.

  14. Notch-1 signaling activates NF-κB in human breast carcinoma MDA-MB-231 cells via PP2A-dependent AKT pathway.

    Science.gov (United States)

    Li, Li; Zhang, Jing; Xiong, Niya; Li, Shun; Chen, Yu; Yang, Hong; Wu, Chunhui; Zeng, Hongjuan; Liu, Yiyao

    2016-04-01

    Breast cancer has a high incidence in the world and is becoming a leading cause of death in female patients due to its high metastatic ability. High expression of Notch-1 and its ligand Jagged-1 correlates with poor prognosis in breast cancer. Our previous work has shown that Notch-1 signaling pathway upregulates NF-κB transcriptional activity and induces the adhesion, migration and invasion of human breast cancer cell line MDA-MB-231. However, the role of Notch-1 in NF-κB activation is still poorly understood. Here, we aim to understand the exact mechanism that Notch-1 regulates NF-κB activity. In MDA-MB-231 cells where Notch-1 is constitutively activated, the phosphorylation of p85 and AKT (Tyr308/Ser473) is upregulated, indicating PI3K/AKT pathway is activated. Notch-1 activation caused the increase of PP2A phosphorylation at Tyr307, indicating Notch-1 inhibits PP2A activity. NF-κB transcriptional activity was evaluated by dual-luciferase reporter assay, and the results showed that, while silencing of Notch-1, PP2A activity was upregulated and NF-κB activity was downregulated, whereas PP2A inhibitor okadaic acid (OA) restored NF-κB activity. Immunofluorescence and Western blots showed that OA treatment antagonized the decrease of p65 nuclear translocation caused by Notch-1 silencing. Moreover, OA treatment also upregulated MMP-2, MMP-9 and VEGF mRNA expression levels, indicating OA rescues Notch-1 silencing that caused low cell invasion. Taken together, our results suggest that Notch-1-activating PI3K/AKT/NF-κB pathway is PP2A dependent; PP2A may be a potential therapeutic target in breast cancer.

  15. 天南星多糖联合顺铂对乳腺癌MDA-MB-231细胞增殖、凋亡及上皮间质转化的影响%Combined Influence of Arisaematis Rhizoma Polysaccharide with Cisplatin on the Proliferation,Apoptosis and Epithelial Mesenchymal Transition of Breast Carcinoma MDA-MB-231 Cells

    Institute of Scientific and Technical Information of China (English)

    邱丽敏; 姜爽

    2016-01-01

    目的:探讨天南星多糖联合顺铂对乳腺癌MDA-MB-231细胞增殖、凋亡及上皮间质转化(EMT)的影响.方法:将MDA-MB-231细胞分为对照组、天南星多糖(50 μg/mL)组、顺铂(5μg/mL)组及联合给药组(天南星多糖+顺铂);MTT法检测细胞增殖,Annexin V/PI双染流式细胞术检测细胞凋亡,Real time PCR法检测EMT相关标记分子(Vimentin、N-cadherin及E-cadherin)mRNA表达,ELISA法检测细胞上清液中纤连蛋白(FN)表达,Western blotring检测Akt及其磷酸化形式(p-Akt)蛋白的表达.结果:天南星多糖组、顺铂组和天南星多糖+顺铂组均可抑制MDA-MB-231细胞的增殖,其作用呈时效关系;各给药组细胞早、晚期凋亡率及E-cadherin mRNA水平值高于对照组,而Vimentin、N-cadherin mRNA、FN水平及p-Akt/Akt显著低于对照组(P<0.05);与天南星多糖组和顺铂组比较,天南星多糖+顺铂组的早、晚期凋亡率及E-cadherin mRNA水平显著升高,Vimentin、N-cadherin mRNA、FN表达水平及p-Akt/Akt显著降低(P<0.05).结论:天南星多糖和顺铂对乳腺癌MDA-MB-231细胞的增殖、凋亡及上皮问质转化均有一定的作用,可抑制PI3K/Akt信号通路的激活,且二者联合作用时效果更好.

  16. Age-dependent association between IgG2 and IgG3 subclasses to Pf332-C231 antigen and protection from malaria, and induction of protective antibodies by sub-patent malaria infections, in Daraweesh

    DEFF Research Database (Denmark)

    Giha, Hayder A; Nasr, Amre; Iriemenam, Nnaemeka C

    2010-01-01

    The certainty of the protective role of acquired immunity in malaria is the major drive for malaria vaccine development. In this study, we measured the levels of total IgG and IgG subclasses to four candidate malaria vaccine antigens; MSP2-3D7, MSP2-FC27, AMA-1 and Pf332-C231, in plasma obtained ...

  17. Phenolic Fractions from Muscadine Grape "Noble" Pomace can Inhibit Breast Cancer Cell MDA-MB-231 Better than those from European Grape "Cabernet Sauvignon" and Induce S-Phase Arrest and Apoptosis.

    Science.gov (United States)

    Luo, Jianming; Wei, Zheng; Zhang, Shengyu; Peng, Xichun; Huang, Yu; Zhang, Yali; Lu, Jiang

    2017-03-22

    Tons of grape pomace which still contained a rich amount of plant polyphenols, is discarded after winemaking. Plant polyphenols have multi-functional activities for human body. In this study, polyphenols of pomaces from Muscadinia rotundifolia "Noble" and Vitis vinifera "Cabernet Sauvignon" were extracted and fractionated, and then they were analyzed with LC-MS and the inhibitory effects on breast cancer cells were compared. The inhibition on MDA-MB-231 cells of fractions from "Noble" was further evaluated. The results showed that polyphenols from 2 grape pomaces could be separated into 3 fractions, and ellagic acid and/or ellagitannins were only detected in fractions from "Noble" pomace. All 3 fractions from "Noble" pomace inhibited MDA-MB-231 better than MCF-7. But fraction 2 from "Cabernet Sauvignon" inhibited MCF-7 better while fraction 1 and fraction 3 inhibited both 2 cells similarly. Moreover, the fractions from "Noble" pomace rather than "Cabernet Sauvignon" can inhibit MDA-MB-231 better. Finally, fractions from "Noble" pomace can induce S-phase arrest and apoptosis on MDA-MB-231. These findings suggested the extracts from grape pomace especially those from "Noble," are potential to be utilized as health beneficial products or even anti-breast cancer agents.

  18. Antrodia salmonea induces G2 cell-cycle arrest in human triple-negative breast cancer (MDA-MB-231) cells and suppresses tumor growth in athymic nude mice.

    Science.gov (United States)

    Chang, Chia-Ting; Hseu, You-Cheng; Thiyagarajan, Varadharajan; Huang, Hui-Chi; Hsu, Li-Sung; Huang, Pei-Jane; Liu, Jer-Yuh; Liao, Jiunn-Wang; Yang, Hsin-Ling

    2017-01-20

    Antrodia salmonea (AS), is a well-known folk medicinal mushroom in Taiwan, has been reported to exhibit anti-oxidant, anti-angiogenic, and anti-inflammatory effects. In the present study, we examined the effects of AS on cell-cycle arrest in vitro in MDA-MB-231 cells and on tumor regression in vivo using an athymic nude mice model. AS (0-200μg/mL) treatment significantly induced G2 cell-cycle arrest in MDA-MB-231 cells by reducing the levels of cyclin B1, cyclin A, cyclin E, and CDC2 proteins. In addition, N-acetylcysteine (NAC) pretreatment prevented AS induced G2 cell-cycle arrest, indicating that ROS accumulation and subsequent cell cycle arrest might be a major mechanism of AS-induced cytotoxicity. Further, AS treatment decreased COX-2 expression and induced PARP cleavage was significantly reversed by NAC pretreatment in MDA-MB-231 cells. The in vivo study results revealed that AS treatment was effective in terms of delaying the tumor incidence and reducing the tumor growth in MDA-MB-231-xenografted nude mice. TUNEL assay, immunohistochemical staining and Western blotting confirmed that AS significantly modulated the xenografted tumor progression as demonstrated by induction of apoptosis, autophagy, and cell-cycle arrest. Our data strongly suggest that Antrodia salmonea could be an anti-cancer agent for human breast cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Vittime del fuoco, tutela preventiva di cui al D.Lgs. 231/01 e tutela risarcitoria / Victims of fire and legal protection / Victimes du feu, tutelle préventive aux termes du D.Lgs. n° 231/01 et indeminisation

    Directory of Open Access Journals (Sweden)

    Fabio Bravo

    2008-04-01

    Full Text Available The present study proceeds from the analysis of the «ThyssenKrupp» case and from the Italian case law and focuses on the legal protection provided by Italian law for the «victims of fire», based both on ex ante protection aiming at preventing the risk of crimes (provided under the legislative decree no. 231/01 and based on organizational models and boards of supervisors and on ex post protection aiming at awarding damages to the victims.Partant de l'affaire "ThyssenKrupp" et de l'étude des cas jurisprudentiels, cet article montre la manière dont le système juridique italien offre aux "victimes du feu" une protection légale sous forme de deux types de tutelle : une forme de prévention aux termes du décret législatif n°231/01 (basée sur divers modèles d'organisation et organismes de contrôle visant à prévenir la perpétration d'actes délictuels et une forme de réparation, impliquant l'indemnisation des victimes.

  20. Methanol extract of Codium fragile inhibits tumor necrosis factor-α-induced matrix metalloproteinase-9 and invasiveness of MDA-MB-231 cells by suppressing nuclear factor-κB activation.

    Science.gov (United States)

    Dilshara, Matharage Gayani; Jayasooriya, Rajapaksha Gedara Prasad Tharanga; Kang, Chang-Hee; Choi, Yung-Hyun; Kim, Gi-Young

    2016-06-01

    To evaluate whether the methanol extract of Codium fragile (MECF) regulates tumor necrosis factor-α (TNF-α)-induced invasion of human breast cancer MDA-MB-231 cells by suppressing matrix metalloproteinase-9 (MMP-9). Reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis were performed to analyze the expression of MMP-9 and nuclear factor-κB (NF-κB) subunits, p65 and p50, and IκB in MDA-MB-231 cells. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used for cell viability. MMP-9 activity and invasion were measured by gelatin zymography and a matrigel invasion assay, respectively. NF-κB activity was measured by an electrophoretic mobility shift assay and luciferase activity. MECF had no effect on cell viability up to a concentration of 100 μg/mL in human breast cancer MDA-MB-231 cells regardless of the presence of TNF-α. MDA-MB-231 cells that were stimulated with TNF-α showed a marked increase of invasion compared to the untreated control, whereas pretreatment with MECF downregulated the TNF-α-induced invasion of MDA-MB-231 cells. Additionally, zymography, western blot analysis, and RT-PCR confirmed that MECF decreased TNF-α-induced MMP-9 expression and activity which is a key regulator for cancer invasion. According to an electrophoretic morbidity shift assay, pretreatment with MECF in MDA-MB-231 cells significantly decreased the TNF-α-induced DNA-binding activity of NF-κB, which is an important transcription factor for regulating cancer invasion-related genes such as MMP-9. Furthermore, treatment with MECF sustained the expression of p65 and p50 in response to TNF-α in the cytosolic compartment. The luciferase assay demonstrated that MECF attenuated TNF-α-induced NF-κB luciferase activity. MECF exhibited its anti-invasive capability by downregulating TNF-α-induced MMP-9 expression, resulting from the suppression of NF-κB activity in the human breast cancer cell line MDA-MB-231

  1. Platycodin D, a metabolite of Platycodin grandiflorum, inhibits highly metastatic MDA-MB-231 breast cancer growth in vitro and in vivo by targeting the MDM2 oncogene.

    Science.gov (United States)

    Kong, Ya; Lu, Zong-Liang; Wang, Jia-Jia; Zhou, Rui; Guo, Jing; Liu, Jie; Sun, Hai-Lan; Wang, He; Song, Wei; Yang, Jian; Xu, Hong-Xia

    2016-09-01

    The objective of the present study was to explore the in vitro and in vivo anticancer effects of Platycodin D (PD), derived from Platycodin grandiflorum, on highly metastatic MDA-MB-231 breast cancer cells. Using the MTT assay, we found that PD inhibited MDA-MB-231 cell growth in a concentration-dependent manner, with an IC50 value of 7.77±1.86 µM. Further studies showed that PD had anti-proliferative effects and induced cell cycle arrest in the G0/G1 phase. To explore the detailed mechanism(s) by which PD suppressed MDA-MB-231 cell growth, western blot analyses were used to detect the expression levels of proteins related to cell proliferation and survival. The data showed that PD decreased the expression of proteins related to the G0/G1 phases, downregulated the protein expression of MDM2, MDMX, and mutant p53, and increased the expression levels of p21 and p27 in vitro. We verified the effects of PD on the expression of MDM2, MDMX, mutant p53, p21 and p27 using a pcDNA3-Flag-MDM2 plasmid and MDM2 siRNA transfection, and found that PD inhibited MDA-MB-231 cell viability by targeting MDM2 and mutant p53. Compared with the corresponding parental cells, the cells with siRNA-MDM2 transfection had a greater decrease in cell viability and proliferation, while those with pcDNA3-MDM2 plasmid transfection did not show any increase in the effects of PD. We also established a MDA-MB-231 xenograft model in BALB/c nude mice, and found that PD significantly inhibited the growth of MDA-MB-231 xenograft tumors in these mice. The expression levels of various proteins in the tumor tissue exhibited changes similar to those observed in vitro. These findings indicate that PD exerted in vitro and in vivo anticancer effects against MDA-MB-231 breast cancer cells, that PD is a potential MDM2/MDMX inhibitor, and that the anticancer effects of PD were likely associated with its inhibition of these proteins. Our observations help to identify a mechanism by which PD functions as

  2. The multi-phase winds of Markarian 231: from the hot, nuclear, ultra-fast wind to the galaxy-scale, molecular outflow

    Science.gov (United States)

    Feruglio, C.; Fiore, F.; Carniani, S.; Piconcelli, E.; Zappacosta, L.; Bongiorno, A.; Cicone, C.; Maiolino, R.; Marconi, A.; Menci, N.; Puccetti, S.; Veilleux, S.

    2015-11-01

    Mrk 231 is a nearby ultra-luminous IR galaxy exhibiting a kpc-scale, multi-phase AGN-driven outflow. This galaxy represents the best target to investigate in detail the morphology and energetics of powerful outflows, as well as their still poorly-understood expansion mechanism and impact on the host galaxy. In this work, we present the best sensitivity and angular resolution maps of the molecular disk and outflow of Mrk 231, as traced by CO(2-1) and (3-2) observations obtained with the IRAM/PdBI. In addition, we analyze archival deep Chandra and NuSTAR X-ray observations. We use this unprecedented combination of multi-wavelength data sets to constrain the physical properties of both the molecular disk and outflow, the presence of a highly-ionized ultra-fast nuclear wind, and their connection. The molecular CO(2-1) outflow has a size of 1 kpc, and extends in all directions around the nucleus, being more prominent along the south-west to north-east direction, suggesting a wide-angle biconical geometry. The maximum projected velocity of the outflow is nearly constant out to 1 kpc, thus implying that the density of the outflowing material must decrease from the nucleus outwards as r-2. This suggests that either a large part of the gas leaves the flow during its expansion or that the bulk of the outflow has not yet reached out to 1 kpc, thus implying a limit on its age of 1 Myr. Mapping the mass and energy rates of the molecular outflow yields dot {M} OF = [500-1000] M⊙ yr-1 and Ėkin,OF = [7-10] × 1043 erg s-1. The total kinetic energy of the outflow is Ekin,OF is of the same order of the total energy of the molecular disk, Edisk. Remarkably, our analysis of the X-ray data reveals a nuclear ultra-fast outflow (UFO) with velocity -20 000 km s-1, dot {M}UFO = [0.3-2.1] M⊙ yr-1, and momentum load dot {P}UFO/ dot {P}rad = [0.2-1.6]. We find Ėkin,UFO Ėkin,OF as predicted for outflows undergoing an energy conserving expansion. This suggests that most of the UFO

  3. The dose dependent in vitro responses of MCF-7 and MDA-MB-231 cell lines to extracts of Vatica diospyroides symington type SS fruit include effects on mode of cell death

    Science.gov (United States)

    Srisawat, Theera; Sukpondma, Yaowapa; Graidist, Potchanapond; Chimplee, Siriphon; Kanokwiroon, Kanyanatt

    2015-01-01

    Background: Vatica diospyroides type LS is a known source of valuable compounds for cancer treatment, however, in contrast little is known about therapeutic efficacy of type SS. Objective: This study focused on in vitro cytotoxicity of these fruit extracts, and the cell death mode they induce in breast cancer cells. Materials and Methods: Acetone extracts of fruit were tested for cytotoxicity against MCF-7 and MDA-MB-231 cell lines. The apoptosis and necrosis of these cells were quantified by fluorescence activated cell sorter (FACS) and western blot analyses. Results: After 72 h of treatment, the 50% growth inhibition concentrations (IC50) levels were 16.21 ± 0.13 µg/mL against MCF-7 and 30.0 ± 4.30 µg/mL against MDA-MB-231, indicating high and moderate cytotoxicity, respectively. From the FACS results, we estimate that the cotyledon extract at half IC50 produced 11.7% dead MCF-7 cells via apoptosis, whereas another concentrations both apoptosis and necrosis modes co-existed in a dose-dependent manner. In MDA-MB-231 cell line, only the apoptosis was induced by the pericarp extract in a dose-dependent manner. With the extracts at half IC50 concentration, in both cells, the expression of p21 decreased while that of Bax increased within 12–48 h of dosing, confirming apoptosis induced by time-dependent responses. Apoptosis dependent on p53 was found in MCF-7, whereas the mutant p53 of MDA-MB-231 cells was expressed. Conclusion: The results indicate that fruit extracts of V. diospyroides have cytotoxic effects against MCF-7 and MDA-MB-231 cells via apoptosis pathway in a dose-dependent manner. This suggests that the extracts could provide active ingredients for the development, targeting breast cancer therapy. PMID:26109760

  4. Inhibition of janus kinase 2 by compound AG490 suppresses the proliferation of MDA-MB-231 cells via up-regulating SARI (suppressor of AP-1, regulated by IFN).

    Science.gov (United States)

    Zhang, Yan-Xia; Yan, Li; Liu, Guang-Yu; Chen, Wen-Jun; Gong, Wei-Hong; Yu, Jin-Ming

    2015-06-01

    The Janus kinase-signal transducers and activators of transcription signaling pathway (JAK/STAT pathway) play an important role in proliferation of breast cancer cells. Previous data showed that inhibition of STAT3 suppresses the growth of breast cancer cells, but the associated mechanisms are not well understood. This study aims to investigate the effect and associated mechanisms of JAK/STAT pathway inhibitor AG490 on proliferation and suppression of breast cancer cells. CCK-8 assay and trypan blue exclusion assay were used to investigate the cytotoxicity of AG490 to MDA-MB-231 cells. Real-time PCR was used to detect the mRNA level of SARI (suppressor of AP-1, regulated by IFN). Western blot was used to analyze the protein levels of SARI, phospho-STAT3 and total STAT3. Luciferase reporter assay was adopted to explore the mechanism of SARI mRNA upregulation. AG490 suppressed the proliferation of MDA-MB-231 cells in a dose-dependent manner. AG490 significantly up-regulated the mRNA and protein levels of SARI in MDA-MB-231 cells. Knockdown of SARI obviously attenuated AG490-induced growth suppression effect in MDA-MB-231 cells. Furthermore, AG490 dramatically enhanced the transcription activity of SARI promoter. But the transcription activity of truncated SARI promoter, which does not contain STAT3 binding site, cannot be activated by AG490 treatment. We demonstrate in this study that AG490 suppresses the proliferation of MDA-MB-231 cells through transcriptional activation of SARI.

  5. Smad2/3-Regulated Expression of DLX2 Is Associated with Radiation-Induced Epithelial-Mesenchymal Transition and Radioresistance of A549 and MDA-MB-231 Human Cancer Cell Lines

    Science.gov (United States)

    Choi, Yeo-Jin; Baek, Ga-Young; Park, Hae-Ran; Jo, Sung-Kee; Jung, Uhee

    2016-01-01

    The control of radioresistance and metastatic potential of surviving cancer cells is important for improving cancer eradication by radiotheraphy. The distal-less homeobox2 (DLX2) gene encodes for a homeobox transcription factor involved in morphogenesis and its deregulation was found in human solid tumors and hematologic malignancies. Here we investigated the role of DLX2 in association with radiation-induced epithelial to mesenchymal transition (EMT) and stem cell-like properties and its regulation by Smad2/3 signaling in irradiated A549 and MDA-MB-231 human cancer cell lines. In irradiated A549 and MDA-MB-231 cells, EMT was induced as demonstrated by EMT marker expression, phosphorylation of Smad2/3, and migratory and invasive ability. Also, irradiated A549 and MDA-MB-231 cells showed increased cancer stem cells (CSCs) marker. Interestingly, DLX2 was overexpressed upon irradiation. Therefore, we examined the role of DLX2 in radiation-induced EMT and radioresistance. The overexpression of DLX2 alone induced EMT, migration and invasion, and CSC marker expression. The reduced colony-forming ability in irradiated cells was partially restored by DLX2 overexpression. On the other hand, the depletion of DLX2 using si-RNA abolished radiation-induced EMT, CSC marker expression, and phosphorylation of Smad2/3 in irradiated A549 and MDA-MB-231 cells. Also, depletion of DLX2 increased the radiation sensitivity in both cell lines. Moreover, knockdown of Smad2/3, a key activator of TGF-β1 pathway, abrogated the radiation-induced DLX2 expression, indicating that radiation-induced DLX2 expression is dependent on Smad2/3 signaling. These results demonstrated that DLX2 plays a crucial role in radioresistance, radiation-induced EMT and CSC marker expression, and the expression of DLX2 is regulated by Smad2/3 signaling in A549 and MDA-MB-231 cell lines. PMID:26799321

  6. Effects of the components of osthole, psoralen, paeonol on breast cancer MDA-MB-231BO cell lines inhibition and TGF-β1 gene expression in vitro%蛇床子素、补骨脂素及丹皮酚配伍对乳腺癌MDA-MB-231BO细胞株的体外抑制及TGF-β1基因表达的影响

    Institute of Scientific and Technical Information of China (English)

    郭保凤; 刘胜; 叶依依; 韩向晖

    2012-01-01

    目的:探讨蛇床子素、补骨脂素及丹皮酚对人乳腺癌高转移MDA-MB-231BO细胞株的体外抑制及侵袭作用的影响,并初步探讨其作用机制.方法:采用均匀设计实验方案进行组方设计;MDA-MB-231BO细胞体外侵袭实验,实时荧光聚合酶链反应( RT-PCR)检测,观察药物处理后细胞的侵袭情况及对人转化生长因子TGF-β1基因的表达情况.结果:获取蛇床子素、补骨脂素、丹皮酚3个药物的最佳配伍比例为10.00:7.78:6.67;单体组和阳性药物组在体外作用24h后,可以显著抑制MDA-MB-231BO细胞的侵袭(P<0.01).结论:中药单体组蛇床子素、补骨脂素、丹皮酚对乳腺癌MDA-MB-231BO细胞的生长具有抑制作用,有效抑制其侵袭和转移,其机制可能与抑制TGF-β1基因的表达有关.%Objective: To study the effects of Osthole, Psoralen, Paeonol on cell lines in vitro on proliferation and invasion of breast cancer MDA-MB-231BO and to study the anti-cancer mechanism of the Chinese Herb active components. Methods: The best combination dose of osthole, psoralen, paeonol on inhibition breast cancer MDA-MB-231BO cell lines in vitro was obtained after adopting the uniform experiment design; MDA-MB-231BO in vitro invasion assay was observed in cell invasion after drug treatment, and Real-time Quantitative RT-PCR experiment was observed the gene expression after drug treatment. Results: The best matched compatibility of Osthol, psoralen, Paeonol was 10.00:7.78:6.67; MDA-MB-231BO cells invasion was significantly inhibited after 24 hours drug treatment by The Chinese monomer groups and Zoledronic acid for injection group; TGF- β 1 gene expression after drug treatment was significantly reduced compared with the control group (P<0.01). Conclusion: The best matched compatibility of osthol, psoralen, paeonol can inhibit the growth of MDA-MB-231BO cells and can effectually inhibit the invasion of MDA-MB-231BO cells in vitro. The mechanism may be related to

  7. 过表达转移抑制基因KAI1对乳腺癌MDA-MB-231细胞上皮间质转化的影响%Effect of non-metastatic gene KAI1 overexpression on epithelial-mesenchymal transition in breast cancer cell line MDA-MB-231

    Institute of Scientific and Technical Information of China (English)

    鞠涛; 金志强

    2015-01-01

    目的:探讨过表达转移抑制基因KAI1对人乳腺癌MDA-MB-231细胞上皮间质转化的影响。方法利用慢病毒感染乳腺癌MDA-MB-231细胞,获得稳定过表达KAI1的细胞系(过表达KAI1组),并设置空白慢病毒感染的阴性对照细胞系(阴性对照组)及未处理的人乳腺癌MDA-MB-231细胞为空白对照组。用Western blot法检测KAI1蛋白过表达的情况;采用RT-PCR法检测过表达KAI1对MDA-MB-231细胞间质标志物(波形蛋白、N-钙黏蛋白和纤粘蛋白)的 mRNA 表达水平的影响;并用Western blot检测过表达KAI1对MDA-MB-231细胞间质标志物(波形蛋白、N-钙黏蛋白)的蛋白表达水平的影响;采用明胶酶谱检测过表达KAI1对MDA-MB-231细胞基质金属蛋白酶2( MMP2)和MMP9活性的影响。多样本均数若满足方差齐性采用单因素方差分析,其两两比较采用LSD法进行,若不满足方差齐性则采用Dunnett’s T3。结果慢病毒感染MDA-MB-231细胞后,各组间AKI1蛋白表达有差异有统计学意义(F=25.610,P=0.001),并且与阴性对照组(0.575±0.065)和空白对照组(0.458±0.0500)相比,过表达KAI1组(0.953±0.034)的KAI1蛋白表达水平明显提高( P均<0.050)。 RT-PCR检测表明,细胞间质标志物波形蛋白(F=10.268,P=0.012)、N-钙黏蛋白(F=32.159,P=0.001)和纤粘蛋白的mRNA(F=38.364,P=0.000)在各组间表达有差异。与阴性对照组(0.937±0.102,0.998±0.064,1.093±0.083)和空白对照组(1.000±0.000,1.000±0.000,1.000±0.000)相比,过表达KAI1组(0.636±0.027,0.576±0.038,0.435±0.051)的波形蛋白、N-钙黏蛋白和纤粘蛋白 mRNA 表达水平明显降低( P 均<0.050),且Western blot检测表明,各组间N-钙黏蛋白(F=9.172,P=0.015)和波形蛋白(F=14.441,P=0.005)表达有差异,与阴性对照组(1.068±0.032)和空白对照组(0.957±0.103)相比,过表达KAI1组(0.597±0.032)的波形蛋白表达水平明显降低(P均<0.050);与阴性对照组(1.452±0.036)和空白对照组(1.403±0

  8. Modulatory effects of heparin and short-length oligosaccharides of heparin on the metastasis and growth of LMD MDA-MB 231 breast cancer cells in vivo.

    Science.gov (United States)

    Mellor, P; Harvey, J R; Murphy, K J; Pye, D; O'Boyle, G; Lennard, T W J; Kirby, J A; Ali, S

    2007-09-17

    Expression of the chemokine receptor CXCR4 allows breast cancer cells to migrate towards specific metastatic target sites which constitutively express CXCL12. In this study, we determined whether this interaction could be disrupted using short-chain length heparin oligosaccharides. Radioligand competition binding assays were performed using a range of heparin oligosaccharides to compete with polymeric heparin or heparan sulphate binding to I(125) CXCL12. Heparin dodecasaccharides were found to be the minimal chain length required to efficiently bind CXCL12 (71% inhibition; PLMD MDA-MB 231 breast cancer cells. In addition, heparin dodecasaccharides were found to have less anticoagulant activity than either a smaller quantity of polymeric heparin or a similar amount of the low molecular weight heparin pharmaceutical product, Tinzaparin. When given subcutaneously in a SCID mouse model of human breast cancer, heparin dodecasaccharides had no effect on the number of lung metastases, but did however inhibit (P<0.05) tumour growth (lesion area) compared to control groups. In contrast, polymeric heparin significantly inhibited both the number (P<0.001) and area of metastases, suggesting a differing mechanism for the action of polymeric and heparin-derived oligosaccharides in the inhibition of tumour growth and metastases.

  9. Resveratrol and Estradiol Exert Disparate Effects on Cell Migration, Cell Surface Actin Structures, and Focal Adhesion Assembly in MDA-MB-231 Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Nicolas G. Azios

    2005-02-01

    Full Text Available Resveratrol, a grape polyphenol, is thought to be a cancer preventive, yet its effects on metastatic breast cancer are relatively unknown. Since cancer cell invasion is dependent on cell migration, the chemotactic response of MDA-MB-231 metastatic human breast cancer cells to resveratrol, estradiol (E2, or epidermal growth factor (EGF was investigated. Resveratrol decreased while E2 and EGF increased directed cell migration. Resveratrol may inhibit cell migration by altering the cytoskeleton. Resveratrol induced a rapid global array of filopodia and decreased focal adhesions and focal adhesion kinase (FAK activity. E2 or EGF treatment did not affect filopodia extension but increased lamellipodia and associated focal adhesions that are integral for cell migration. Combined resveratrol and E2 treatment resulted in a filopodia and focal adhesion response similar to resveratrol alone. Combined resveratrol and EGF resulted in a lamellipodia and focal adhesion response similar to EGF alone. E2 and to a lesser extent resveratrol increased EGFR activity. The cytoskeletal changes and EGFR activity in response to E2 were blocked by EGFR1 inhibitor indicating that E2 may increase cell migration via crosstalk with EGFR signaling. These data suggest a promotional role for E2 in breast cancer cell migration but an antiestrogenic, preventative role for resveratrol.

  10. The conditioned medium from osteo-differentiating human mesenchymal stem cells affects the viability of triple negative MDA-MB231 breast cancer cells.

    Science.gov (United States)

    Librizzi, Mariangela; Tobiasch, Edda; Luparello, Claudio

    2016-01-01

    This study aimed to investigate the effect of conditioned media (CM) from osteo-differentiating and adipo-differentiating human mesenchymal stem cells (MSCs) isolated from lipoaspirates of healthy female donors on the viability of triple-negative breast cancer cells MDA-MB231. The CM of undifferentiated and differentiating MSCs were collected after 7, 14, 21 and 28 days of culture. The effects of MSC CM on cell proliferation were assessed using an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay after 24 h. The effects of osteo-differentiating cell CM on apoptotic promotion, cell cycle impairment, mitochondrial transmembrane potential dissipation, production of reactive oxygen species and autophagosome accumulation were analysed by flow cytometry and Western blot. MTT assay showed that only CM collected from osteo-induced cells at day 28 (d28O-CM) reduced tumour cell viability. Treatment with d28O-CM restrained cell cycle progression through G2 phase, elicited a caspase-8-driven apoptotic effect already after 5 h of culture, and down-regulated autophagosome accumulation and beclin-1 expression. The finding that factor(s) secreted by osteo-differentiating MSCs shows properties of an apoptotic inducer and autophagy inhibitor on triple-negative breast cancer cells may have an important applicative potential that deserves further investigation.

  11. Combined effects of furanodiene and doxorubicin on the migration and invasion of MDA-MB-231 breast cancer cells in vitro.

    Science.gov (United States)

    Zhong, Zhang-Feng; Tan, Wen; Tian, Ke; Yu, Hua; Qiang, Wen-An; Wang, Yi-Tao

    2017-04-01

    Furanodiene is one of the major bioactive components isolated from the natural product of the plant, Curcuma wenyujin Y.H. Chen et C. Ling. Furanodiene has been found to exert anticancer effects in various types of cancer cell lines, as well as exhibit antimetastatic activities. However, the antimetastatic capacity of furanodiene in combination with the common chemotherapy drug doxorubicin has not been investigated. We found that doxorubicin at a non-toxic concentration induced cell migration and cell invasion in highly metastatic breast cancer cells. Combinational treatments with furanodiene and doxorubicin blocked the invasion and migration of MDA-MB-231 breast cancer cells in vitro. We also clarified the effects of the combination on the signaling pathways involved in migration, invasion, and cytoskeletal organization. When combined with doxorubicin, furanodiene downregulated the expression of integrin αV and β-catenin and inhibited the phosphorylation of paxillin, Src, focal adhesion kinase (FAK), p85, and Akt. Moreover, combinational treatments also resulted in a decrease in matrix metalloproteinase-9 (MMP-9). Further study demonstrated that the co-treatments with furanodiene did not significantly alter the effects of doxorubicin on the tubulin cytoskeleton, represented by no influence on the expression levels of RhoA, Cdc42, N-WASP, and α/β tubulin. These observations indicate that furanodiene is a potential agent that may be utilized to improve the anticancer efficacy of doxorubicin and overcome the risk of chemotherapy in highly metastatic breast cancer.

  12. Ganoderiol A-enriched extract suppresses migration and adhesion of MDA-MB-231 cells by inhibiting FAK-SRC-paxillin cascade pathway.

    Directory of Open Access Journals (Sweden)

    Guo-Sheng Wu

    Full Text Available Cell adhesion, migration and invasion are critical steps for carcinogenesis and cancer metastasis. Ganoderma lucidum, also called Lingzhi in China, is a traditional Chinese medicine, which exhibits anti-proliferation, anti-inflammation and anti-metastasis properties. Herein, GAEE, G. lucidum extract mainly contains ganoderiol A (GA, dihydrogenated GA and GA isomer, was shown to inhibit the abilities of adhesion and migration, while have a slight influence on that of invasion in highly metastatic breast cancer MDA-MB-231 cells at non-toxic doses. Further investigation revealed that GAEE decreased the active forms of focal adhesion kinase (FAK and disrupted the interaction between FAK and SRC, which lead to deactivating of paxillin. Moreover, GAEE treatment downregulated the expressions of RhoA, Rac1, and Cdc42, and decreased the interaction between neural Wiskott-Aldrich Syndrome protein (N-WASP and Cdc42, which impair cell migration and actin assembly. To our knowledge, this is the first report to show that G.lucidum triterpenoids could suppress cell migration and adhesion through FAK-SRC-paxillin signaling pathway. Our study also suggests that GAEE may be a potential agent for treatment of breast cancer.

  13. Acalypha indica Linn: Biogenic synthesis of silver and gold nanoparticles and their cytotoxic effects against MDA-MB-231, human breast cancer cells

    Directory of Open Access Journals (Sweden)

    C. Krishnaraj

    2014-12-01

    Full Text Available This study reports the in vitro cytotoxic effect of biologically synthesized silver and gold nanoparticles against MDA-MB-231, human breast cancer cells. Formation of silver and gold nanoparticles was observed within 30 min and the various characterization techniques such as UV–vis spectrophotometer, FE-SEM, TEM and XRD studies were confirmed the synthesis of nanoparticles. Further, MTT, acridine orange and ethidium bromide (AO/EB dual staining, caspase-3 and DNA fragmentation assays were carried out using various concentrations of silver and gold nanoparticles ranging from 1 to 100 μg/ml. At 100 μg/ml concentration, the plant extract derived nanoparticles exhibited significant cytotoxic effects and the apoptotic features were confirmed through caspase-3 activation and DNA fragmentation assays. Thus, the results of the present study indicate that biologically synthesized silver and gold nanoparticles might be used to treat breast cancer; however, it necessitates clinical studies to ascertain their potential as anticancer agents.

  14. Accumulation of GD1α Ganglioside in MDA-MB-231 Breast Cancer Cells Expressing ST6GalNAc V.

    Science.gov (United States)

    Vandermeersch, Sandy; Vanbeselaere, Jorick; Delannoy, Clément P; Drolez, Aurore; Mysiorek, Caroline; Guérardel, Yann; Delannoy, Philippe; Julien, Sylvain

    2015-04-16

    α-Series gangliosides define a particular sub-class of glycosphingolipids containing sialic acid α2,6-linked to GalNAc residue that was isolated as a minor compound from the brain. The sialyltransferase ST6GalNAc V was cloned from mouse brain and showed α2,6-sialyltransferase activity almost exclusively for GM1b, to form GD1α and is considered as the main enzyme involved in the biosynthesis of α-series gangliosides. Recently, ST6GALNAC5 was identified as one of the genes over-expressed in breast cancer cell populations selected for their ability to produce brain metastasis. However, the capacity of human breast cancer cells to produce α-series gangliosides has never been clearly demonstrated. Here, we show by stable transfection and MS-MS analysis of total glycosphingolipids that ST6GALNAC5 expressing MDA-MB-231 breast cancer cells accumulate GD1α ganglioside (IV3Neu5Ac1, III6Neu5Ac1Gg4-Cer).

  15. Accumulation of GD1α Ganglioside in MDA-MB-231 Breast Cancer Cells Expressing ST6GalNAc V

    Directory of Open Access Journals (Sweden)

    Sandy Vandermeersch

    2015-04-01

    Full Text Available α-Series gangliosides define a particular sub-class of glycosphingolipids containing sialic acid α2,6-linked to GalNAc residue that was isolated as a minor compound from the brain. The sialyltransferase ST6GalNAc V was cloned from mouse brain and showed α2,6-sialyltransferase activity almost exclusively for GM1b, to form GD1α and is considered as the main enzyme involved in the biosynthesis of α-series gangliosides. Recently, ST6GALNAC5 was identified as one of the genes over-expressed in breast cancer cell populations selected for their ability to produce brain metastasis. However, the capacity of human breast cancer cells to produce α-series gangliosides has never been clearly demonstrated. Here, we show by stable transfection and MS-MS analysis of total glycosphingolipids that ST6GALNAC5 expressing MDA-MB-231 breast cancer cells accumulate GD1α ganglioside (IV3Neu5Ac1, III6Neu5Ac1Gg4-Cer.

  16. AGN-driven winds on all scales in Markarian 231: from hot nuclear ultra-fast up to kpc-extended molecular outflow

    CERN Document Server

    Feruglio, C; Carniani, S; Piconcelli, E; Zappacosta, L; Bongiorno, A; Cicone, C; Maiolino, R; Marconi, A; Menci, N; Puccetti, S; Veilleux, S

    2015-01-01

    We present the best sensitivity and angular resolution maps of the molecular disk and outflow of Mrk231, obtained with IRAM/PdBI, and an analysis of archival Chandra and NuSTAR data. We constrain the physical properties of both the molecular disk and outflow, the presence of a highly-ionized ultra-fast nuclear wind, and their connection. The CO(2-1) outflow has a size of ~1 kpc, and extends in all directions around the nucleus, being more prominent along the south-west to north-east direction, suggesting a wide-angle biconical geometry. Its maximum projected velocity is nearly constant out to ~1 kpc, thus implying that the density of the outflowing material must decrease from the nucleus outwards as ~ r^-2. This suggests that either a large part of the gas leaves the flow during its expansion, or that the bulk of the outflow has not yet reached ~1 kpc, implying a limit on its age of ~ 1 Myr. The mass and energy rates of the molecular outflow are dM/dt(OF)=[500-1000] Msun/yr and dE(kin,OF)/dt=[7-10] 10^43 erg/...

  17. The Complete Ultraviolet Spectrum of the Archetypal "Wind-Dominated" Quasar Mrk~231: Absorption and Emission from a High-Speed Dusty Nuclear Outflow

    CERN Document Server

    Veilleux, S; Tripp, T M; Hamann, F; Rupke, D S N

    2016-01-01

    New near- and far-ultraviolet (NUV and FUV) HST spectra of Mrk 231, the nearest quasar known, are combined with ground-based optical spectra to study the remarkable dichotomy between the FUV and NUV-optical spectral regions in this object. The FUV emission-line features are faint, broad, and highly blueshifted (up to ~7000 km/s), with no significant accompanying absorption. In contrast, the profiles of the NUV absorption features resemble those of the optical Na I D, He I, and Ca II H and K lines, exhibiting broad blue-shifted troughs that overlap in velocity space with the FUV emission-line features and indicate a dusty, high-density and patchy broad absorption line (BAL) screen covering ~90% of the observed continuum source at a distance less than ~2 - 20 pc. The FUV continuum emission does not show the presence of any obvious stellar features and is remarkably flat compared with the steeply declining NUV continuum. The NUV (FUV) features and continuum emission have not varied significantly over the past ~2...

  18. Catalysis and pH control by membrane-associated carbonic anhydrase IX in MDA-MB-231 breast cancer cells.

    Science.gov (United States)

    Li, Ying; Tu, Chingkuang; Wang, Hai; Silverman, David N; Frost, Susan C

    2011-05-06

    Carbonic anhydrase IX (CAIX) is a membrane-bound, tumor-related enzyme whose expression is often considered a marker for hypoxia, an indicator of poor prognosis in the majority of cancer patients, and is associated with acidification of the tumor microenvironment. Here, we describe for the first time the catalytic properties of native CAIX in MDA-MB-231 breast cancer cells that exhibit hypoxia-inducible CAIX expression. Using (18)O exchange measured by membrane inlet mass spectrometry, we determined catalytic activity in membrane ghosts and intact cells. Exofacial carbonic anhydrase activity increases with exposure to hypoxia, an activity which is suppressed by impermeant sulfonamide CA inhibitors. Inhibition by sulfonamide inhibitors is not sensitive to reoxygenation. CAIX activity in intact cells increases in response to reduced pH. Data from membrane ghosts show that the increase in activity at reduced pH is largely due to an increase in the dehydration reaction. In addition, the kinetic constants of CAIX in membrane ghosts are very similar to our previous measurements for purified, recombinant, truncated forms. Hence, the activity of CAIX is not affected by the proteoglycan extension or membrane environment. These activities were measured at a total concentration for all CO(2) species at 25 mm and close to chemical equilibrium, conditions which approximate the physiological extracellular environment. Our data suggest that CAIX is particularly well suited to maintain the extracellular pH at a value that favors the survival fitness of tumor cells.

  19. Type-Ia Supernova Remnant Shell At $Z=3.5$ Seen In The Three Sightlines Toward The Gravitationally Lensed Qso B1422+231

    CERN Document Server

    Hamano, Satoshi; Kondo, Sohei; Tsujimoto, Takuji; Okoshi, Katsuya; Shigeyama, Toshikazu

    2012-01-01

    Using the Subaru 8.2m Telescope with an IRCS Echelle spectrograph, we obtained high-resolution (R=10,000) near-infrared (1.01-1.38 \\mu m) spectra of images A and B of the gravitationally lensed QSO B1422+231 (z=3.628) consisting of four known lensed images. We detected MgII absorption lines at z=3.54, which show a large variance of column densities (~ 0.3 dex) and velocities (~ 10 km/s) between the sightlines A and B with a projected separation of only 8.4h_{70}^{-1} pc at the redshift. This is the smallest spatial structure of the high-z gas clouds ever detected after Rauch et al. found a 20-pc scale structure for the same z=3.54 absorption system using optical spectra of images A and C. The observed systematic variances imply that the system is an expanding shell as originally suggested by Rauch et al. By combining the data for three sightlines, we managed to constrain the radius and expansion velocity of the shell (~ 50-100 pc, 130 km/s), concluding that the shell is truly a supernova remnant (SNR) rather ...

  20. BAC-FISH refutes report of an 8p22–8p23.1 inversion or duplication in 8 patients with Kabuki syndrome

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    Hobart Holly H

    2006-05-01

    Full Text Available Abstract Background Kabuki syndrome is a multiple congenital anomaly/mental retardation syndrome. The syndrome is characterized by varying degrees of mental retardation, postnatal growth retardation, distinct facial characteristics resembling the Kabuki actor's make-up, cleft or high-arched palate, brachydactyly, scoliosis, and persistence of finger pads. The multiple organ involvement suggests that this is a contiguous gene syndrome but no chromosomal anomalies have been isolated as an etiology. Recent studies have focused on possible duplications in the 8p22–8p23.1 region but no consensus has been reached. Methods We used bacterial artificial chromosome-fluorescent in-situ hybridization (BAC-FISH and G-band analysis to study eight patients with Kabuki syndrome. Results Metaphase analysis revealed no deletions or duplications with any of the BAC probes. Interphase studies of the Kabuki patients yielded no evidence of inversions when using three-color FISH across the region. These results agree with other research groups' findings but disagree with the findings of Milunsky and Huang. Conclusion It seems likely that Kabuki syndrome is not a contiguous gene syndrome of the 8p region studied.

  1. Beneficial effects of a medicinal herb, Cirsium japonicum var. maackii, extract and its major component, cirsimaritin on breast cancer metastasis in MDA-MB-231 breast cancer cells.

    Science.gov (United States)

    Yeon Park, Jun; Young Kim, Hyun; Shibamoto, Takayuki; Su Jang, Tae; Cheon Lee, Sang; Suk Shim, Jae; Hahm, Dae-Hyun; Lee, Hae-Jeung; Lee, Sanghyun; Sung Kang, Ki

    2017-09-01

    The biological activities of the ethanol extract from Cirsium japonicum var. maackii (ICF-1) and its major component, polyphenol cirsimaritin, were investigated as part of the search for possible alternative drugs for breast cancer. Three in vitro cell-based assays were used: the cell proliferation assay, tube-formation assay, and Western blot analysis. Both the ICF-1 extract and cirsimaritin inhibited the viability of HUVECs in a dose-dependent manner. The inhibition achieved was 36.89% at a level of 200μg/ml by the ICF-1 extract and 62.04% at a level of 100μM by cirsimaritin. The ICF-1 extract and cirsimaritin reduced tube formation by 12.69% at level of 25μg/ml and 32.18% at the levels of 6.25μM, respectively. Cirsimaritin inhibited angiogenesis by downregulation of VEGF, p-Akt and p-ERK in MDA-MB-231 cells, suggesting that cirsimaritin is potentially useful as an anti-metastatic agent. The present study demonstrated that Cirsium japonicum extract and its active component cirsimaritin is an excellent candidate as an alternative anti-breast cancer drug. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Salinomycin Promotes Anoikis and Decreases the CD44+/CD24- Stem-Like Population via Inhibition of STAT3 Activation in MDA-MB-231 Cells.

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    Hyunsook An

    Full Text Available Triple-negative breast cancer (TNBC is an aggressive tumor subtype with an enriched CD44+/CD24- stem-like population. Salinomycin is an antibiotic that has been shown to target cancer stem cells (CSC; however, the mechanisms of action involved have not been well characterized. The objective of the present study was to investigate the effect of salinomycin on cell death, migration, and invasion, as well as CSC-like properties in MDA-MB-231 breast cancer cells. Salinomycin significantly induced anoikis-sensitivity, accompanied by caspase-3 and caspase-8 activation and PARP cleavage, during anchorage-independent growth. Salinomycin treatment also caused a marked suppression of cell migration and invasion with concomitant downregulation of MMP-9 and MMP-2 mRNA levels. Notably, salinomycin inhibited the formation of mammospheres and effectively reduced the CD44+/CD24- stem-like population during anchorage-independent growth. These observations were associated with the inhibition of STAT3 phosphorylation (Tyr705. Furthermore, interleukin-6 (IL-6-induced STAT3 activation was strongly suppressed by salinomycin challenge. These findings support the notion that salinomycin may be potentially efficacious for targeting breast cancer stem-like cells through the inhibition of STAT3 activation.

  3. Salinomycin Promotes Anoikis and Decreases the CD44+/CD24- Stem-Like Population via Inhibition of STAT3 Activation in MDA-MB-231 Cells.

    Science.gov (United States)

    An, Hyunsook; Kim, Ji Young; Oh, Eunhye; Lee, Nahyun; Cho, Youngkwan; Seo, Jae Hong

    2015-01-01

    Triple-negative breast cancer (TNBC) is an aggressive tumor subtype with an enriched CD44+/CD24- stem-like population. Salinomycin is an antibiotic that has been shown to target cancer stem cells (CSC); however, the mechanisms of action involved have not been well characterized. The objective of the present study was to investigate the effect of salinomycin on cell death, migration, and invasion, as well as CSC-like properties in MDA-MB-231 breast cancer cells. Salinomycin significantly induced anoikis-sensitivity, accompanied by caspase-3 and caspase-8 activation and PARP cleavage, during anchorage-independent growth. Salinomycin treatment also caused a marked suppression of cell migration and invasion with concomitant downregulation of MMP-9 and MMP-2 mRNA levels. Notably, salinomycin inhibited the formation of mammospheres and effectively reduced the CD44+/CD24- stem-like population during anchorage-independent growth. These observations were associated with the inhibition of STAT3 phosphorylation (Tyr705). Furthermore, interleukin-6 (IL-6)-induced STAT3 activation was strongly suppressed by salinomycin challenge. These findings support the notion that salinomycin may be potentially efficacious for targeting breast cancer stem-like cells through the inhibition of STAT3 activation.

  4. Removal of polycyclic aromatic hydrocarbons in soil spiked with model mixtures of petroleum hydrocarbons and heterocycles using biosurfactants from Rhodococcus ruber IEGM 231.

    Science.gov (United States)

    Ivshina, Irina; Kostina, Ludmila; Krivoruchko, Anastasiya; Kuyukina, Maria; Peshkur, Tatyana; Anderson, Peter; Cunningham, Colin

    2016-07-15

    Removal of polycyclic aromatic hydrocarbons (PAHs) in soil using biosurfactants (BS) produced by Rhodococcus ruber IEGM 231 was studied in soil columns spiked with model mixtures of major petroleum constituents. A crystalline mixture of single PAHs (0.63g/kg), a crystalline mixture of PAHs (0.63g/kg) and polycyclic aromatic sulfur heterocycles (PASHs), and an artificially synthesized non-aqueous phase liquid (NAPL) containing PAHs (3.00g/kg) dissolved in alkanes C10-C19 were used for spiking. Percentage of PAH removal with BS varied from 16 to 69%. Washing activities of BS were 2.5 times greater than those of synthetic surfactant Tween 60 in NAPL-spiked soil and similar to Tween 60 in crystalline-spiked soil. At the same time, amounts of removed PAHs were equal and consisted of 0.3-0.5g/kg dry soil regardless the chemical pattern of a model mixture of petroleum hydrocarbons and heterocycles used for spiking. UV spectra for soil before and after BS treatment were obtained and their applicability for differentiated analysis of PAH and PASH concentration changes in remediated soil was shown. The ratios A254nm/A288nm revealed that BS increased biotreatability of PAH-contaminated soils.

  5. Effects of NRP-1 Overexpression on Biological Behaviors of Breast Cancer Cell Lines MDA-MB-231 and SK-BR-3%NRP-1过表达对乳腺癌细胞MDA-MB-231、SK-BR-3生物学行为的影响

    Institute of Scientific and Technical Information of China (English)

    张梦瑾; 徐杰; 王红梅; 杜秀平; 韩正祥

    2016-01-01

    目的 通过上调乳腺癌细胞MDA-MB-231、SK-BR-3中NRP-1的表达,观察NRP-1对细胞增殖、凋亡、迁移及侵袭能力的影响.方法 构建pcDNA3.1-NRP-1表达载体,脂质体介导NRP-1表达质粒转染MDA-MB-231、SK-BR-3细胞,用G418筛选出稳定转染的乳腺癌细胞株.利用RT-qPCR、Western blot法分别检测NRP-1基因mRNA及其蛋白表达;CCK-8法、AnnexinⅤ-APC/7-AAD法、Transwell小室分别检测转染细胞增殖率、凋亡率及侵袭、迁移能力.结果 成功构建pcDNA3.1-NRP-1表达载体,转染MDA-MB-231、SK-BR-3细胞并筛选稳定表达系.与对照组相比,过表达组细胞的NRP-1 mRNA及蛋白表达水平明显升高(均P<0.05);NRP-1过表达组的细胞较对照组增殖率增加、凋亡率降低、侵袭及迁移能力增强(均P<0.05).结论 NRP-1在乳腺癌发展、浸润、转移中起着一定的作用,它可促进乳腺癌细胞增殖、迁移和侵袭,抑制其凋亡.

  6. 5-氮杂-2’-脱氧胞苷对MDA-MB-231乳腺癌细胞SLIT2基因去甲基化作用及细胞运动能力的影响%5-Aza-dc induces demethylation in Slit2 promoter gene and inhibits the motility ability of MDA-MB-231 cell line

    Institute of Scientific and Technical Information of China (English)

    张姣; 付丽; 谷峰; 马勇杰

    2012-01-01

    目的 观察5-氮杂-2’-脱氧胞苷( 5-Aza-dc)对恶性乳腺癌MDA-MB-231细胞Slit2启动子的去甲基化作用及细胞运动能力的影响.方法 用5、10、20 μmol/L 5-Aza-dc分别处理MDA-MB-231乳腺癌细胞;噻唑蓝(MTT)比色法筛选能够恢复MDA-MB-231细胞Slit2表达的5-Azadc最适浓度为10 μmol/L;逆转录-聚合酶链反应(RT-PCR)检测对照组和10μmol/L处理组Slit2mRNA的表达;划痕实验和趋化实验检测5-Aza-dc给药后,乳腺癌细胞的非定向与定向运动能力的变化;聚集实验检测5 -Aza-dc对MDA-MB-231细胞间黏附能力的影响.结果 在RT-PCR结果中,对照组和10 μmol/L 5-Aza-dc处理组Slit2/GAPDH的密度比值分别为0.630±0.042和1.307±0.057,表明5-Aza-dc可有效恢复乳腺癌MDA-MB-231细胞Slit2的表达(P<0.05).体外趋化实验显示10 μmol/L 5-Aza-dc处理的MDA-MB-231细胞定向运动能力降低(P<0.01),趋化凶子上皮生长因子(EGF)浓度为10 μg/L时实验组穿过膜的细胞数为49.46±2.92;对照组为99.44±2.54.伤口愈合实验发现10μmol/L 5-Aza-dc处理的MDA-MB-231细胞非定向运动能力降低(P<0.05),24h时实验组运动的距离为(0.330±0.016) mm;对照组为(0.440±0.045) mm.聚集实验显示10 μmol/L 5-Aza-dc处理的MDA-MB-231细胞间黏附能力增加(P<0.01),60 min时实验组聚集指数为0.300±0.028,对照组为0.600±0.034.结论 5-Aza-dc可以使MDA-MB-231乳腺癌细胞Slit2启动子区去甲基化,使Slit2基因表达升高,恢复其抑制肿瘤运动的能力.%Objective To observe the transcription regulation of 5-Aza-dc on Slit2 tumor suppressor gene in human breast cancer MDA-MB-231 cell line and to investigate its effect on the motility ability of MDA-MB-231 cells.Methods Human breast cancer MDA-MB-231 cells were treated with 5,10,20 μ mol/L 5-Aza-dc respectively.The optical concentration of 5-Aza-dc chosen by methyl thiazol tetrazolium (MTT) assay was 10 μmol/L.Reverse transcription polymerase chain

  7. Synthesis of new cis-fused tetrahydrochromeno[4,3-b]quinolines and their antiproliferative activity studies against MDA-MB-231 and MCF-7 breast cancer cell lines.

    Science.gov (United States)

    Nagaiah, K; Venkatesham, A; Srinivasa Rao, R; Saddanapu, V; Yadav, J S; Basha, S J; Sarma, A V S; Sridhar, B; Addlagatta, A

    2010-06-01

    New cis-fused tetrahydrochromeno[4,3-b]quinolines have been synthesized by intramolecular [4+2] imino-Diels-Alder reactions of 2-azadienes derived in situ from aromatic amines and 7-O-prenyl derivatives of 8-formyl-2,3-disubstituted chromenones in the presence of 20mol% Yb(OTf)(3) in acetonitrile under reflux conditions in good to excellent yields. The structures were established by spectroscopic data and further confirmed by X-ray diffraction analysis. These compounds were evaluated for their antiproliferative activity against MDA-MB-231 and MCF-7 breast cancer cells. The results showed that compounds 3e, 3f, and 3k exhibit significant antiproliferative activity against MCF-7 breast cancer cells and low inhibitory activity against MDA-MB-231 breast cancer cell lines. Compound 3h displayed activity as comparable to tamoxifen on both the cell lines.

  8. ESTRATÉGIAS DE RESPONSABILIDADE SOCIAL CORPORATIVA: UM ESTUDO SOBRE OS 231 CASOS CONCRETOS DO INSTITUTO ETHOS [doi: 10.5329/RECADM.20060501004

    Directory of Open Access Journals (Sweden)

    Franciara Maria de Oliveira

    2006-05-01

    Full Text Available ResumoUm perfil das estratégias de Responsabilidade Social Corporativa adotadas por empresas no Brasil é o objetivoprincipal deste trabalho. Utilizou-se como universo de estudo os 231 Casos Concretos preenchidosespontaneamente pelas empresas filiadas na página web do Instituto Ethos de Empresa e ResponsabilidadeSocial (Instituto Ethos. Os casos foram analisados pelo software alemão de análise de dados qualitativosdenominado Atlas.ti 5.0, sob o enfoque metodológico das seis variáveis adotadas por Kotler e Lee (2005 emCorporate Social Responsability: doing the most good for your company and your cause, como estratégias paraalcançar-se a Responsabilidade Social Corporativa. As estratégias analisadas são: Marketing SocialCorporativo, Marketing de Causa Social, Patrocínio, Filantropia Estratégica, Voluntariado Corporativo e AçãoSocial Responsável. Percebe-se que a maioria das empresas que divulgaram suas estratégias deResponsabilidade Social ainda não tem a percepção plena da utilização dessas estratégias, haja vista que agrande maioria ainda está classificada com Ação Social Responsável, vindo em seguida o Marketing SocialCorporativo, Filantropia Estratégica, Voluntariado Corporativo, Patrocínio e Marketing de Causa SocialPalavras-chave: Estratégias. Marketing. Responsabilidade Social Corporativa.AbstractA profile of the strategies of Corporate Social Responsibility adopted by companies in Brazil is the main objectiveof this work. It was used as study universe the 231 Concrete Cases filled of spontaneous form for thecompanies registered in the web page of the Ethos Institute of Company and Social Responsibility (EthosInstitute. The cases had been analyzed by the German software of analysis of qualitative data called Atlas.ti5.0, under the methodical approach of the six variable adopted for Kotler and Lee (2005 in Corporate SocialResponsability: doing the most good for your company and your cause, as strategies to reach

  9. Northern Pintail Telemetry [ds231

    Data.gov (United States)

    California Department of Resources — Using radio-telemetry, female northern pintail (Anas acuta) survival, distribution, and movements during late August-March in Central California were determined...

  10. Distinct Biochemical Pools of Golgi Phosphoprotein 3 in the Human Breast Cancer Cell Lines MCF7 and MDA-MB-231

    Science.gov (United States)

    Luchsinger, Charlotte; Rivera-Dictter, Andrés; Arriagada, Cecilia; Acuña, Diego; Aguilar, Marcelo; Cavieres, Viviana; Burgos, Patricia V.; Ehrenfeld, Pamela; Mardones, Gonzalo A.

    2016-01-01

    Golgi phosphoprotein 3 (GOLPH3) has been implicated in the development of carcinomas in many human tissues, and is currently considered a bona fide oncoprotein. Importantly, several tumor types show overexpression of GOLPH3, which is associated with tumor progress and poor prognosis. However, the underlying molecular mechanisms that connect GOLPH3 function with tumorigenicity are poorly understood. Experimental evidence shows that depletion of GOLPH3 abolishes transformation and proliferation of tumor cells in GOLPH3-overexpressing cell lines. Conversely, GOLPH3 overexpression drives transformation of primary cell lines and enhances mouse xenograft tumor growth in vivo. This evidence suggests that overexpression of GOLPH3 could result in distinct features of GOLPH3 in tumor cells compared to that of non-tumorigenic cells. GOLPH3 is a peripheral membrane protein mostly localized at the trans-Golgi network, and its association with Golgi membranes depends on binding to phosphatidylinositol-4-phosphate. GOLPH3 is also contained in a large cytosolic pool that rapidly exchanges with Golgi-associated pools. GOLPH3 has also been observed associated with vesicles and tubules arising from the Golgi, as well as other cellular compartments, and hence it has been implicated in several membrane trafficking events. Whether these and other features are typical to all different types of cells is unknown. Moreover, it remains undetermined how GOLPH3 acts as an oncoprotein at the Golgi. Therefore, to better understand the roles of GOLPH3 in cancer cells, we sought to compare some of its biochemical and cellular properties in the human breast cancer cell lines MCF7 and MDA-MB-231 with that of the non-tumorigenic breast human cell line MCF 10A. We found unexpected differences that support the notion that in different cancer cells, overexpression of GOLPH3 functions in diverse fashions, which may influence specific tumorigenic phenotypes. PMID:27123979

  11. Colorectal cancer risk variants at 8q23.3 and 11q23.1 are associated with disease phenotype in APC mutation carriers.

    Science.gov (United States)

    Ghorbanoghli, Z; Nieuwenhuis, M H; Houwing-Duistermaat, J J; Jagmohan-Changur, S; Hes, F J; Tops, C M; Wagner, A; Aalfs, C M; Verhoef, S; Gómez García, E B; Sijmons, R H; Menko, F H; Letteboer, T G; Hoogerbrugge, N; van Wezel, T; Vasen, H F A; Wijnen, J T

    2016-10-01

    Familial adenomatous polyposis (FAP) is a dominantly inherited syndrome caused by germline mutations in the APC gene and characterized by the development of multiple colorectal adenomas and a high risk of developing colorectal cancer (CRC). The severity of polyposis is correlated with the site of the APC mutation. However, there is also phenotypic variability within families with the same underlying APC mutation, suggesting that additional factors influence the severity of polyposis. Genome-wide association studies identified several single nucleotide polymorphisms (SNPs) that are associated with CRC. We assessed whether these SNPs are associated with polyp multiplicity in proven APC mutation carriers. Sixteen CRC-associated SNPs were analysed in a cohort of 419 APC germline mutation carriers from 182 families. Clinical data were retrieved from the Dutch Polyposis Registry. Allele frequencies of the SNPs were compared for patients with colorectal adenomas versus patients with ≥100 adenomas, using generalized estimating equations with the APC genotype as a covariate. We found a trend of association of two of the tested SNPs with the ≥100 adenoma phenotype: the C alleles of rs16892766 at 8q23.3 (OR 1.71, 95 % CI 1.05-2.76, p = 0.03, dominant model) and rs3802842 at 11q23.1 (OR 1.51, 95 % CI 1.03-2.22, p = 0.04, dominant model). We identified two risk variants that are associated with a more severe phenotype in APC mutation carriers. These risk variants may partly explain the phenotypic variability in families with the same APC gene defect. Further studies with a larger sample size are recommended to evaluate and confirm the phenotypic effect of these SNPs in FAP.

  12. Influence of washing and quenching in profiling the metabolome of adherent mammalian cells: a case study with the metastatic breast cancer cell line MDA-MB-231.

    Science.gov (United States)

    Kapoore, Rahul Vijay; Coyle, Rachael; Staton, Carolyn A; Brown, Nicola J; Vaidyanathan, Seetharaman

    2017-06-07

    Metabolome characterisation is a powerful tool in oncology. To obtain a valid description of the intracellular metabolome, two of the preparatory steps are crucial, namely washing and quenching. Washing must effectively remove the extracellular media components and quenching should stop the metabolic activities within the cell, without altering the membrane integrity of the cell. Therefore, it is important to evaluate the efficiency of the washing and quenching solvents. In this study, we employed two previously optimised protocols for simultaneous quenching and extraction, and investigated the effects of a number of washing steps/solvents and quenching solvent additives, on metabolite leakage from the adherent metastatic breast cancer cell line MDA-MB-231. We explored five washing protocols and five quenching protocols (including a control for each), and assessed for effectiveness by detecting ATP in the medium and cell morphology changes through scanning electron microscopy (SEM) analyses. Furthermore, we studied the overall recovery of eleven different metabolite classes using the GC-MS technique and compared the results with those obtained from the ATP assay and SEM analysis. Our data demonstrate that a single washing step with PBS and quenching with 60% methanol supplemented with 70 mM HEPES (-50 °C) results in minimum leakage of intracellular metabolites. Little or no interference of PBS (used in washing) and methanol/HEPES (used in quenching) on the subsequent GC-MS analysis step was noted. Together, these findings provide for the first time a systematic study into the washing and quenching steps of the metabolomics workflow for studying adherent mammalian cells, which we believe will improve reliability in the application of metabolomics technology to study adherent mammalian cell metabolism.

  13. Distinct Biochemical Pools of Golgi Phosphoprotein 3 in the Human Breast Cancer Cell Lines MCF7 and MDA-MB-231.

    Directory of Open Access Journals (Sweden)

    María J Tenorio

    Full Text Available Golgi phosphoprotein 3 (GOLPH3 has been implicated in the development of carcinomas in many human tissues, and is currently considered a bona fide oncoprotein. Importantly, several tumor types show overexpression of GOLPH3, which is associated with tumor progress and poor prognosis. However, the underlying molecular mechanisms that connect GOLPH3 function with tumorigenicity are poorly understood. Experimental evidence shows that depletion of GOLPH3 abolishes transformation and proliferation of tumor cells in GOLPH3-overexpressing cell lines. Conversely, GOLPH3 overexpression drives transformation of primary cell lines and enhances mouse xenograft tumor growth in vivo. This evidence suggests that overexpression of GOLPH3 could result in distinct features of GOLPH3 in tumor cells compared to that of non-tumorigenic cells. GOLPH3 is a peripheral membrane protein mostly localized at the trans-Golgi network, and its association with Golgi membranes depends on binding to phosphatidylinositol-4-phosphate. GOLPH3 is also contained in a large cytosolic pool that rapidly exchanges with Golgi-associated pools. GOLPH3 has also been observed associated with vesicles and tubules arising from the Golgi, as well as other cellular compartments, and hence it has been implicated in several membrane trafficking events. Whether these and other features are typical to all different types of cells is unknown. Moreover, it remains undetermined how GOLPH3 acts as an oncoprotein at the Golgi. Therefore, to better understand the roles of GOLPH3 in cancer cells, we sought to compare some of its biochemical and cellular properties in the human breast cancer cell lines MCF7 and MDA-MB-231 with that of the non-tumorigenic breast human cell line MCF 10A. We found unexpected differences that support the notion that in different cancer cells, overexpression of GOLPH3 functions in diverse fashions, which may influence specific tumorigenic phenotypes.

  14. Inositol hexaphosphate (IP6) inhibits key events of cancer metastasis: I. In vitro studies of adhesion, migration and invasion of MDA-MB 231 human breast cancer cells.

    Science.gov (United States)

    Tantivejkul, Kwanchanit; Vucenik, Ivana; Shamsuddin, Abulkalam M

    2003-01-01

    The anti-cancer agent inositol hexaphosphate (IP6) is an abundant intrinsic component of both plant and mammalian cells. In addition to inducing differentiation and inhibiting growth of numerous cancer cell lines in vitro, IP6 has been demonstrated to prevent and abrogate both primary tumor and metastasis in vivo. Using MDA-MB 231 human breast cancer cells, we studied the potential of IP6 to inhibit cell adhesion, migration and invasion, the key steps in cancer metastasis, utilizing the extracellular matrix (ECM) proteins, a culture wounding assay, modified Boyden chambers, immunocytochemistry and zymography. IP6 treatment caused a 65% reduction of cell adhesion to fibronection (p = 0.002) and a 37% reduction to collagen (p = 0.005). To determine whether a decrease in cell adhesion leads to a decrease in cell motility, migration assays were performed; IP6 decreased both the number of migrating cells and the distance of cell migration into the denuded area by 72% (p IP6-treated cells as compared to untreated cells, corresponding to a diminished ability of cancer cells to form cellular network as determined by Matrigel outgrowth assay. Likewise, cell invasion also was decreased (by 72% after IP6 treatment, p = 0.001) in a dose-dependent fashion. Additionally, IP6 significantly (p = 0.006) inhibited the secretion of matrix metalloproteinase (MMP)-9 as assessed by zymography. The results of this study show that IP6 inhibits the metastasis of human breast cancer cells in vitro through effects on cancer cell adhesion, migration and invasion.

  15. MicroRNA-125b induces metastasis by targeting STARD13 in MCF-7 and MDA-MB-231 breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Feng Tang

    Full Text Available MicroRNAs (miRNAs are a class of small noncoding RNAs that regulate gene expression by targeting mRNAs to trigger either translation repression or mRNA degradation. miR-125b is down-regulated in human breast cancer cells compared with the normal ones except highly metastatic tumor cells MDA-MB-231. However, few functional studies were designed to investigate metastatic potential of miR-125b. In this study, the effects of miR-125b on metastasis in human breast cancer cells were studied, and the targets of miR-125b were also explored. Transwell migration assay, cell wound healing assay, adhesion assay and nude mice model of metastasis were utilized to investigate the effects of miR-125b on metastasis potential in vitro and in vivo. In addition, it was implied STARD13 (DLC2 was a direct target of miR-125b by Target-Scan analysis, luciferase reporter assay and western blot. Furthermore, activation of STARD13 was identified responsible for metastasis induced by miR-125b through a siRNA targeting STARD13. qRT-PCR, immunofluorescent assay and western blot was used to observe the variation of Vimentin and α-SMA in breast cancer cells. In summary, our study provided new insights into the function of miR-125b during the metastasis of breat cancer cells and also suggested the role of miR-125b in pro-metastasis by targeting STARD13.

  16. MicroRNA-125b induces metastasis by targeting STARD13 in MCF-7 and MDA-MB-231 breast cancer cells.

    Science.gov (United States)

    Tang, Feng; Zhang, Rui; He, Yunmian; Zou, Meijuan; Guo, Le; Xi, Tao

    2012-01-01

    MicroRNAs (miRNAs) are a class of small noncoding RNAs that regulate gene expression by targeting mRNAs to trigger either translation repression or mRNA degradation. miR-125b is down-regulated in human breast cancer cells compared with the normal ones except highly metastatic tumor cells MDA-MB-231. However, few functional studies were designed to investigate metastatic potential of miR-125b. In this study, the effects of miR-125b on metastasis in human breast cancer cells were studied, and the targets of miR-125b were also explored. Transwell migration assay, cell wound healing assay, adhesion assay and nude mice model of metastasis were utilized to investigate the effects of miR-125b on metastasis potential in vitro and in vivo. In addition, it was implied STARD13 (DLC2) was a direct target of miR-125b by Target-Scan analysis, luciferase reporter assay and western blot. Furthermore, activation of STARD13 was identified responsible for metastasis induced by miR-125b through a siRNA targeting STARD13. qRT-PCR, immunofluorescent assay and western blot was used to observe the variation of Vimentin and α-SMA in breast cancer cells. In summary, our study provided new insights into the function of miR-125b during the metastasis of breat cancer cells and also suggested the role of miR-125b in pro-metastasis by targeting STARD13.

  17. Assessment of Interactions between Cisplatin and Two Histone Deacetylase Inhibitors in MCF7, T47D and MDA-MB-231 Human Breast Cancer Cell Lines – An Isobolographic Analysis

    OpenAIRE

    Anna Wawruszak; Luszczki, Jarogniew J; Aneta Grabarska; Ewelina Gumbarewicz; Magdalena Dmoszynska-Graniczka; Krzysztof Polberg; Andrzej Stepulak

    2015-01-01

    Histone deacetylase inhibitors (HDIs) are promising anticancer drugs, which inhibit proliferation of a wide variety of cancer cells including breast carcinoma cells. In the present study, we investigated the influence of valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA, vorinostat), alone or in combination with cisplatin (CDDP) on proliferation, induction of apoptosis and cell cycle progression in MCF7, T47D and MDA-MB-231 human breast carcinoma cell lines. The type of interactio...

  18. Thymoquinone-Loaded Nanostructured Lipid Carrier Exhibited Cytotoxicity towards Breast Cancer Cell Lines (MDA-MB-231 and MCF-7 and Cervical Cancer Cell Lines (HeLa and SiHa

    Directory of Open Access Journals (Sweden)

    Wei Keat Ng

    2015-01-01

    Full Text Available Thymoquinone (TQ has been shown to exhibit antitumor properties. Thymoquinone-loaded nanostructured lipid carrier (TQ-NLC was developed to improve the bioavailability and cytotoxicity of TQ. This study was conducted to determine the cytotoxic effects of TQ-NLC on breast cancer (MDA-MB-231 and MCF-7 and cervical cancer cell lines (HeLa and SiHa. TQ-NLC was prepared by applying the hot high pressure homogenization technique. The mean particle size of TQ-NLC was 35.66 ± 0.1235 nm with a narrow polydispersity index (PDI lower than 0.25. The zeta potential of TQ-NLC was greater than −30 mV. Polysorbate 80 helps to increase the stability of TQ-NLC. Differential scanning calorimetry showed that TQ-NLC has a melting point of 56.73°C, which is lower than that of the bulk material. The encapsulation efficiency of TQ in TQ-NLC was 97.63 ± 0.1798% as determined by HPLC analysis. TQ-NLC exhibited antiproliferative activity towards all the cell lines in a dose-dependent manner which was most cytotoxic towards MDA-MB-231 cells. Cell shrinkage was noted following treatment of MDA-MB-231 cells with TQ-NLC with an increase of apoptotic cell population (P<0.05. TQ-NLC also induced cell cycle arrest. TQ-NLC was most cytotoxic towards MDA-MB-231 cells. It induced apoptosis and cell cycle arrest in the cells.

  19. Arctigenin, a lignan from Arctium lappa L., inhibits metastasis of human breast cancer cells through the downregulation of MMP-2/-9 and heparanase in MDA-MB-231 cells.

    Science.gov (United States)

    Lou, Chenghua; Zhu, Zhihui; Zhao, Yaping; Zhu, Rui; Zhao, Huajun

    2017-01-01

    Arctigenin is a bioactive lignan isolated from the seeds of Arctium lappa L. which has been widely used as a diuretic and a diaphoretic in Traditional Chinese Medicine. In the present study, the authors investigated the effects of arctigenin on tumor migration and invasion in aggressive human breast cancer cells. The MTT assay results showed that arctigenin did not show a significant cytotoxic effect on the cell viability of MDA-MB-231 cells. However, wound healing migration and Boyden chamber invasion assays demonstrated that arctigenin significantly inhibited in vitro migration and invasion of the MDA-MB-231 cells. Furthermore, gelatin zymography results showed that arctigenin reduced the activity of MMP-2 and MMP-9. Western blot analysis results demonstrated that the expression of MMP-2, MMP-9 and heparanase proteins was significantly downregulated following the treatment of arctigenin. Finally, the antiangiogenic activity of arctigenin was also examined by the chick embryo chorioallantoic membrane (CAM) assay. Arctigenin treatment significantly inhibited angiogenesis in the CAM. In conclusion, the results revealed that arctigenin significantly inhibited the migration and invasion of MDA-MB-231 cells by downregulating MMP-2, MMP-9 and heparanase expression. However, further studies are still necessary to investigate the exact mechanisms involved and to explore signal transduction pathways to better understand the biological mechanisms.

  20. Photodynamic damage of carcinophotorin on breast cancer cells MDA-MB-231 and its mechanism%癌光啉对人乳腺癌细胞MDA-MB-231的光动力杀伤效应及其机制研究

    Institute of Scientific and Technical Information of China (English)

    陈磊; 孔祥杰; 李佳; 张俊峰; 房林

    2013-01-01

    Objective: This study aims to evaluate the efficacy of carcinophotorin (PSD-007) photosensitization on the apopto-sis-induced response in human breast cancer cells and analyze the mechanisms of PSD-007 involved in this process. Methods: Methyl thiazolyl tetrazolium (MTT) assay and in situ labeling were performed to examine the effects of the photodynamic therapy (PDT) on the proliferation and apoptosis of the cancer cells MDA-MB-231, respectively. Changes in cellular morphology were assessed using an optical microscope. Real-time polymerase chain reaction and Western blot analysis were conducted to clarify the underlying mecha-nisms. Results: The MTT assay revealed that at a concentration of 10 μg/mL and in combination with 9.0 J/cm2 laser radiation power 24 h after cell culture, PSD-007 markedly inhibited the proliferation of breast tumor cells, with an inhibition rate of 97.01%." Under a fluorescent microscope, apoptotic cells in the treatment groups with 5 and 10 μg/mL PSD-007-PDT were observed to have dramatically outnumbered the control groups. The dead cells after PSD-007-PDT mainly consisted of necrotic and late apoptotic cells. Caspase-3, caspase-8, P65, and P53 expression was upregulated in the treatment groups compared with the control group, with 5 and 10 μg/ml PSD-007 therapies, whereas no significant alteration in Bcl-2 and Bcl-x was found. Conclusion: PDT inhibits the proliferation and in-duces the apoptosis of cancer cells MDA-MB-231 by upregulating the caspase-3, caspase-8, P53, and NF-KB pathways, indicating a new strategy for treating breast cancer in the future.%  目的:探讨癌光啉(PSD-007)在体外对于乳腺癌细胞株MDA-MB-231光动力杀伤效应,并分析其分子机制.方法:MTT法检测不同浓度PSD-007(0、2、4、6、8、10μg/mL)作用于MDA-MB-231细胞株后对其增殖的影响;光学显微镜下观察光动力治疗后细胞形态的变化,荧光显微镜分析PSD-007作用后细胞

  1. ApoG2诱导乳腺癌细胞 MDA -MB231自噬的最低浓度探讨%Rational use of ApoG2 through autophagy inhibition exploiting and apoptosis inducing in breast cancer MDA -MB231 cells

    Institute of Scientific and Technical Information of China (English)

    陈可绪; 汪森明; 曹漫明; 胡喜钢

    2015-01-01

    目的:探究不同浓度棉酚衍生物 ApoG2对乳腺癌细胞株 MDA -MB231诱导自噬的最低浓度,寻找抗肿瘤效应的最适合浓度。方法:CCK8法检测细胞的增殖活性;透射电镜下观察细胞超微结构;流式细胞仪检测细胞凋亡及周期阻滞情况;细胞免疫荧光法检测各组细胞 LC3-II 荧光强度;RT -PCR 及 Western blot 法检测细胞自噬蛋白 LC3-I 及 LC3-II 表达强度。结果:CCK8法示 ApoG2对乳腺癌 MDA -MB231细胞呈浓度、时间依赖性抑制增殖且各组间差异存在统计学意义;透射电镜下发现 ApoG2可诱导凋亡及自噬;流式细胞仪检测发现 ApoG2诱导凋亡呈浓度依赖性,使细胞周期阻滞于 S 期且10μmol/L 浓度组最明显;细胞免疫荧光法发现10μmol/L 组细胞 LC3-II 荧光最弱;RT -PCR 及 Western blot 法示细胞自噬蛋白 LC3-I 表达各组间无明显差异,LC3-II 在10μmol/L 浓度组表达量最弱,80μmol/L 浓度组表达量最强。结论:10μmol/L 为ApoG2诱导乳腺癌细胞 MDA -MB231自噬最低浓度,也是抑制自噬,促进凋亡的抗肿瘤最适浓度。%Objective:To investigate the rational dose of Apogosspolone by inhibiting antophagy in anticancer ther-apy.Methods:Qualitative verification of apoptosis and autophagy was conducted with transmission electron micro-scope.Semi -quantitative determination of autophapy was performed by immunofluorescence staining,flow cytometry, and quantitative determination of autophagy by CCK8,real -time polymerase chain reaction,Western blotting.Re-sults:CCK8 showed ApoG2 was at inhibition proliferation in concentration and time dependence for MDA -MB231 of brest cancer.It was found that ApoG2 can induce apoptosis and autophagy under the transmission electron micro-scope.ApoG2 induced apoptosis with concentration dependence and arrested in S stage for cell cycle,with obvious-ness in 10μmol/L group.Immunofluorescence staining

  2. MDA-MB-231细胞源exosome对人脐静脉内皮细胞(HUVEC)VEGF自分泌及体外成管作用的影响%Effects of exosomes derived from MDA-MB-231 on the expression of autocrine VEGF and capillary-like tube formation in HUVECs

    Institute of Scientific and Technical Information of China (English)

    隆霜; 沈宜; 谢莹珊; 范维珂; 姜蓉; 陈黎

    2012-01-01

    目的 研究人乳腺癌MDA-MB-231细胞源exosome对人脐静脉内皮细胞(human umbilical vein endothelial cell,HUVEC)血管内皮生长因子(vascular endothelial growth factor,VEGF)自分泌及体外成管作用的影响,探讨肿瘤细胞源exosome在肿瘤微环境中对血管内皮细胞血管生成的调控作用.方法 低温超速离心及密度梯度离心法提取乳腺癌MDA-MB-231细胞源exosome;酶联免疫吸附试验(ELISA)检测HUVEC与exosome共培养24 h后上清液中VEGF的变化水平;Western blot技术检测HUVEC与exosome共培养24 h后VEGF、VEGFR2及p-VEGFR2的蛋白表达情况;RT-PCR法检测HUVEC与exosome共培养24 h后VEGF的基因表达情况;观察HUVEC与exosome共培养24 h后的体外成管能力.结果 HUVEC与exosome共培养24 h后上清液中VEGF为(110.851±18.404)pg/mL,与对照组相比差异具有统计学意义(P<0.05);Western blot结果显示,HUVEC与exosome共培养24 h后VEGF和p-VEGFR2的蛋白表达水平均增加(P<0.05);RT-PCR结果显示,HUVEC与exosome共培养24 h后VEGF的基因表达水平增加(P<0.05);体外成管实验显示,exosome显著提高了HUVEC的管腔形成能力(P<0.05).结论 乳腺癌MDA-MB-231细胞源exosome促进了血管内皮细胞VEGF的表达及分泌,激活了血管内皮细胞VEGF/VEGFR2自分泌环并提高了血管内皮细胞的体外成管能力,对促肿瘤血管生成有一定的调控作用.%Objective To investigate the effects of exosomes derived from breast cancer cell line MDA-MB-231 on the expression of autocrine vascular endothelial growth factor (VEGF) and capillary-like tube formation in human umbilical vein endothelial cells ( HUVECs) , and to observe the regulatory effect of exosomes derived from cancer cells on angiogenesis in tumor microenvironment. Methods Exosomes were purified by serial ultracentrifugation and sugar density ultracentrifugation. The expression of autocrine VEGF in HUVECs with exosomes co-cultured 24 hours were detected by

  3. 5-氮杂-2'-脱氧胞苷与顺铂对MDA-MB-231细胞的联合作用%Effect of combining treatment of 5-Aza-CdR and cisplatin on MDA-MB-231 cells

    Institute of Scientific and Technical Information of China (English)

    沈三弟; 陈卓荣; 肖高芳; 刘彦明

    2013-01-01

    目的 探讨5-氮杂-2'-脱氧胞苷(5-Aza-CdR,DAC)与顺铂(cisplatin,PDD)联合应用对人三阴性乳腺癌细胞株MDA-MB-231体外增殖及凋亡的影响.方法实验分组:5 μM DAC处理组(DAC组),15 μM PDD处理组(PDD组),2.5 μM DAC与8 μM PDD同步处理组(DAC+PDD组),2.5 μM DAC与8 μM PDD序贯处理组(DAC→PDD组)及空白对照组.分别以MTT法和流式细胞术(FCM)测定各处理组MDA-MB-231细胞的增殖、凋亡情况,以q值评价两药的联合效应.结果 DAC组的24 h、48 h、72 h增殖抑制率分别为(8.12±0.79)%、(21.72±1.60)%及(30.39±1.31)%;PDD组为(35.14±2.00)%、(49.22±1.01)%及(65.52±1.53)%;DAC+PDD组为(54.25±3.82)%、(68.89±1.52)%及(87.26±2.37)%;DAC→PDD组为(6.84±0.68)%、(67.64±0.91)%及(88.76±3.54)%.联合组较单药组增殖抑制率均显著升高(P<0.01).DAC+PDD组、DAC→PDD组24 h、48 h、72 h的q值分别为1.12、1.14、1.15和0、1.12、1.17,两药联合有增效作用.对照组、DAC组、PDD组、DAC+PDD组、DAC→PDD组24 h、48 h、72 h凋亡率分别为(1.57±0.38)%、(1.83±0.27)%、(2.26±0.42)%;(10.41±0.70)%、(15.37±0.74)%、(21.39±1.22)%;(16.63±0.65)%、(21.89±1.20)%、(30.39±2.20)%;(21.42±1.11)%、(33.86±1.16)%、(42.92±1.16)%;(8.26±0.68)%、(28.98±1.01)%、(41.98±1.12)%.联合组较单药组及对照组凋亡率显著升高(P<0.01).结论 DAC与PDD均能抑制MDA-MB-231细胞株的增殖,促进其凋亡,且两者联合有增效作用.

  4. 重组人促红细胞生成素对人乳腺癌MDA-MB-231细胞增殖的影响及其作用机制研究

    Institute of Scientific and Technical Information of China (English)

    晋雯; 孔令英; 张小容; 杨丽

    2013-01-01

    目的 探讨重组人促红细胞生成素(recombinant human erythropoietin,rh-EPO)对人乳腺癌MDA-MB-231细胞增殖的影响及其作用机制.方法 将人乳腺癌 MDA-MB-231 细胞进行培养.传至5~6代,细胞生长状态稳定后,收集人乳腺癌 MDA-MB-231细胞用于MTT实验.采用MTT法检测 5 组(阴性对照组、rh-EPO A 组、rh-EPO B组、rh-EPO C 组和rh-EPO D 组)MDA-MB-231细胞增殖的情况.用10 μmol·L-1p38MAPK抑制剂SB203580、ERK抑制剂U0126、JNK抑制剂SP600125和NF-κB 抑制剂PDTC预处理人乳腺癌 MDA-MB-231 细胞后,用MTT法检测经100、200、300和400 U·mL-1的rh-EPO(PDTC+EPO 组、SB203580+EPO 组、SP600125+EPO组和U0126+EPO组)诱导后细胞增殖的情况.结果 阴性对照组、rh-EPO A 组、rh-EPO B组、rh-EPO C 组和rh-EPO D 组 72 h PI值分别为:1.000 0±1.000 0、1.231 8±0.133 0、1.323 9±0.136 0、1.351 7±0.146 0和1.423 1±0.084 0;96 h PI值分别为:1.000 0±1.000 0、1.352 5±0.036 0、1.359 7±0.112 0、1.387 2±0.063 0和1.410 8±0.060 0.rh-EPO A 组、rh-EPO B组、rh-EPO C 组和rh-EPO D 组 72、96 h PI值与阴性对照组比较差异均有统计学意义(均P<0.05).PDTC+EPO 组、SB203580+EPO 组72、96 h PI值均较EPO组明显降低(均P<0.05),SP600125+EPO组、U0126+EPO组72、96 h PI值与EPO组比较差异均无统计学意义(均P>0.05).结论 rh-EPO可能是通过NF-κB、MAPK传导通路发挥效应,促进人乳腺癌MDA-MB-231细胞增殖.

  5. 乳腺癌细胞-干细胞共培养上清液对乳腺癌细胞的体外抗肿瘤作用研究%Antitumer effect of supernatant from co-culture of human embryonic stem cells and breast cancer cells on MDA-MB-231 cells in vitro

    Institute of Scientific and Technical Information of China (English)

    郑良栋; 冯涛; 何雪梅; 张婷; 刘梦楠; 廖红

    2016-01-01

    研究人胚胎干细胞H9与肿瘤细胞MDA-MB-231共培养上清液对乳腺癌MDA-MB-231细胞的抑制作用.建立人胚胎干细胞H9与乳腺癌MDA-MB-231细胞接触式共培养体系,收集共培养上清液.以单独培养的H9细胞上清为对照,显微镜下观察共培养上清液对肿瘤细胞生物行为学的影响,用MTT法检测上清液对MDA-MB-231细胞增殖能力的影响,Hoechst染色及流式细胞术检测上清液对肿瘤细胞的凋亡影响;transwell小室法检测上清液对肿瘤细胞迁移及侵袭的影响.结果显示,共培养上清液能抑制MDA-MB-231细胞增殖,促进其凋亡,抑制肿瘤细胞的侵袭和迁移,而单独培养的H9细胞上清液对MDA-MB-231细胞几乎没有影响.因此得出结论,人胚胎干细胞H9与人乳腺癌MDA-MB-231细胞共培养的上清液对MDA-MB-231有一定的体外抑癌效应.

  6. Propofol induces proliferation partially via downregulation of p53 protein and promotes migration via activation of the Nrf2 pathway in human breast cancer cell line MDA-MB-231.

    Science.gov (United States)

    Meng, Chao; Song, Linlin; Wang, Juan; Li, Di; Liu, Yanhong; Cui, Xiaoguang

    2017-02-01

    Antioxidants induce the proliferation of cancers by decreasing the expression of p53. Propofol, one of the most extensively used intravenous anesthetics, provides its antioxidative activity via activation of the nuclear factor E2-related factor-2 (Nrf2) pathway, but the mechanisms involved in the effects remain unknown. Thus, we aimed to investigate the function of p53 and Nrf2 in the human breast cancer cell line MDA-MB-231 following treatment with propofol. The cells were treated with propofol (2, 5 and 10 µg/ml) for 1, 4 and 12 h, and MTT assay was used to evaluate cell proliferation, and a wound healing assay was used to evaluate cell migration. Cell apoptosis, caspase-3 activity, and western blot analysis for p53 and Nrf2 protein were also assessed. Finally, PIK-75, a potent Nrf2 inhibitor, was used to confirm the effects of Nrf2 after treatment with propofol. Treatment of MDA-MB‑231 cells with propofol resulted in increased proliferation and migration in a dose- and time-dependent manner. After treatment with propofol for 12 h, the Nrf2 protein expression was increased, while the percentage of apoptotic cells, caspase-3 activity, and expression of p53 were significantly decreased. Additionally, treatment with the Nrf2 inhibitor increased the percentage of apoptotic cells, inhibited the migration almost completely, and decreased the degree of proliferation, while the expression of p53 was not affected. In conclusion, propofol increased the proliferation of human breast cancer MDA-MB‑231 cells, which was at least partially associated with the inhibition of the expression of p53, and induced cell migration, which was involved in the activation of the Nrf2 pathway.

  7. Genomic, proteomic and morphological characterization of two novel broad host lytic bacteriophages ΦPD10.3 and ΦPD23.1 infecting pectinolytic Pectobacterium spp. and Dickeya spp.

    Science.gov (United States)

    Czajkowski, Robert; Ozymko, Zofia; de Jager, Victor; Siwinska, Joanna; Smolarska, Anna; Ossowicki, Adam; Narajczyk, Magdalena; Lojkowska, Ewa

    2015-01-01

    Pectinolytic Pectobacterium spp. and Dickeya spp. are necrotrophic bacterial pathogens of many important crops, including potato, worldwide. This study reports on the isolation and characterization of broad host lytic bacteriophages able to infect the dominant Pectobacterium spp. and Dickeya spp. affecting potato in Europe viz. Pectobacterium carotovorum subsp. carotovorum (Pcc), P. wasabiae (Pwa) and Dickeya solani (Dso) with the objective to assess their potential as biological disease control agents. Two lytic bacteriophages infecting stains of Pcc, Pwa and Dso were isolated from potato samples collected from two potato fields in central Poland. The ΦPD10.3 and ΦPD23.1 phages have morphology similar to other members of the Myoviridae family and the Caudovirales order, with a head diameter of 85 and 86 nm and length of tails of 117 and 121 nm, respectively. They were characterized for optimal multiplicity of infection, the rate of adsorption to the Pcc, Pwa and Dso cells, the latent period and the burst size. The phages were genotypically characterized with RAPD-PCR and RFLP techniques. The structural proteomes of both phages were obtained by fractionation of phage proteins by SDS-PAGE. Phage protein identification was performed by liquid chromatography-mass spectrometry (LC-MS) analysis. Pulsed-field gel electrophoresis (PFGE), genome sequencing and comparative genome analysis were used to gain knowledge of the length, organization and function of the ΦPD10.3 and ΦPD23.1 genomes. The potential use of ΦPD10.3 and ΦPD23.1 phages for the biocontrol of Pectobacterium spp. and Dickeya spp. infections in potato is discussed.

  8. Synthesis, Characterization, and Study of In Vitro Cytotoxicity of ZnO-Fe3O4 Magnetic Composite Nanoparticles in Human Breast Cancer Cell Line (MDA-MB-231) and Mouse Fibroblast (NIH 3T3).

    Science.gov (United States)

    Bisht, Gunjan; Rayamajhi, Sagar; Kc, Biplab; Paudel, Siddhi Nath; Karna, Deepak; Shrestha, Bhupal G

    2016-12-01

    Novel magnetic composite nanoparticles (MCPs) were successfully synthesized by ex situ conjugation of synthesized ZnO nanoparticles (ZnO NPs) and Fe3O4 NPs using trisodium citrate as linker with an aim to retain key properties of both NPs viz. inherent selectivity towards cancerous cell and superparamagnetic nature, respectively, on a single system. Successful characterization of synthesized nanoparticles was done by XRD, TEM, FTIR, and VSM analyses. VSM analysis showed similar magnetic profile of thus obtained MCPs as that of naked Fe3O4 NPs with reduction in saturation magnetization to 16.63 emu/g. Also, cell viability inferred from MTT assay showed that MCPs have no significant toxicity towards noncancerous NIH 3T3 cells but impart significant toxicity at similar concentration to breast cancer cell MDA-MB-231. The EC50 value of MCPs on MDA-MB-231 is less than that of naked ZnO NPs on MDA-MB-231, but its toxicity on NIH 3T3 was significantly reduced compared to ZnO NPs. Our hypothesis for this prominent difference in cytotoxicity imparted by MCPs is the synergy of selective cytotoxicity of ZnO nanoparticles via reactive oxygen species (ROS) and exhausting scavenging activity of cancerous cells, which further enhance the cytotoxicity of Fe3O4 NPs on cancer cells. This dramatic difference in cytotoxicity shown by the conjugation of magnetic Fe3O4 NPs with ZnO NPs should be further studied that might hold great promise for the development of selective and site-specific nanoparticles. Schematic representation of the conjugation, characterization and cytotoxicity analysis of Fe3O4-ZnO magnetic composite particles (MCPs).

  9. Synthesis, Characterization, and Study of In Vitro Cytotoxicity of ZnO-Fe3O4 Magnetic Composite Nanoparticles in Human Breast Cancer Cell Line (MDA-MB-231) and Mouse Fibroblast (NIH 3T3)

    Science.gov (United States)

    Bisht, Gunjan; Rayamajhi, Sagar; KC, Biplab; Paudel, Siddhi Nath; Karna, Deepak; Shrestha, Bhupal G.

    2016-12-01

    Novel magnetic composite nanoparticles (MCPs) were successfully synthesized by ex situ conjugation of synthesized ZnO nanoparticles (ZnO NPs) and Fe3O4 NPs using trisodium citrate as linker with an aim to retain key properties of both NPs viz. inherent selectivity towards cancerous cell and superparamagnetic nature, respectively, on a single system. Successful characterization of synthesized nanoparticles was done by XRD, TEM, FTIR, and VSM analyses. VSM analysis showed similar magnetic profile of thus obtained MCPs as that of naked Fe3O4 NPs with reduction in saturation magnetization to 16.63 emu/g. Also, cell viability inferred from MTT assay showed that MCPs have no significant toxicity towards noncancerous NIH 3T3 cells but impart significant toxicity at similar concentration to breast cancer cell MDA-MB-231. The EC50 value of MCPs on MDA-MB-231 is less than that of naked ZnO NPs on MDA-MB-231, but its toxicity on NIH 3T3 was significantly reduced compared to ZnO NPs. Our hypothesis for this prominent difference in cytotoxicity imparted by MCPs is the synergy of selective cytotoxicity of ZnO nanoparticles via reactive oxygen species (ROS) and exhausting scavenging activity of cancerous cells, which further enhance the cytotoxicity of Fe3O4 NPs on cancer cells. This dramatic difference in cytotoxicity shown by the conjugation of magnetic Fe3O4 NPs with ZnO NPs should be further studied that might hold great promise for the development of selective and site-specific nanoparticles.

  10. Synthesis and in vitro anti-proliferative activity of some novel isatins conjugated with quinazoline/phthalazine hydrazines against triple-negative breast cancer MDA-MB-231 cells as apoptosis-inducing agents.

    Science.gov (United States)

    Eldehna, Wagdy M; Almahli, Hadia; Al-Ansary, Ghada H; Ghabbour, Hazem A; Aly, Mohamed H; Ismael, Omnia E; Al-Dhfyan, Abdullah; Abdel-Aziz, Hatem A

    2017-12-01

    Treatment of patients with triple-negative breast cancer (TNBC) is challenging due to the absence of well- defined molecular targets and the heterogeneity of such disease. In our endeavor to develop potent isatin-based anti-proliferative agents, we utilized the hybrid-pharmacophore approach to synthesize three series of novel isatin-based hybrids 5a-h, 10a-h and 13a-c, with the prime goal of developing potent anti-proliferative agents toward TNBC MDA-MB-231 cell line. In particular, compounds 5e and 10g were the most active hybrids against MDA-MB-231 cells (IC50 = 12.35 ± 0.12 and 12.00 ± 0.13 μM), with 2.37- and 2.44-fold increased activity than 5-fluorouracil (5-FU) (IC50 = 29.38 ± 1.24 μM). Compounds 5e and 10g induced the intrinsic apoptotic mitochondrial pathway in MDA-MB-231; evidenced by the reduced expression of the anti-apoptotic protein Bcl-2, the enhanced expression of the pro-apoptotic protein Bax and the up-regulated active caspase-9 and caspase-3 levels. Furthermore, 10g showed significant increase in the percent of annexin V-FITC positive apoptotic cells from 3.88 to 31.21% (8.4 folds compared to control).

  11. Genomic, proteomic and morphological characterization of two novel broad host lytic bacteriophages ΦPD10.3 and ΦPD23.1 infecting pectinolytic Pectobacterium spp. and Dickeya spp.

    Directory of Open Access Journals (Sweden)

    Robert Czajkowski

    Full Text Available Pectinolytic Pectobacterium spp. and Dickeya spp. are necrotrophic bacterial pathogens of many important crops, including potato, worldwide. This study reports on the isolation and characterization of broad host lytic bacteriophages able to infect the dominant Pectobacterium spp. and Dickeya spp. affecting potato in Europe viz. Pectobacterium carotovorum subsp. carotovorum (Pcc, P. wasabiae (Pwa and Dickeya solani (Dso with the objective to assess their potential as biological disease control agents. Two lytic bacteriophages infecting stains of Pcc, Pwa and Dso were isolated from potato samples collected from two potato fields in central Poland. The ΦPD10.3 and ΦPD23.1 phages have morphology similar to other members of the Myoviridae family and the Caudovirales order, with a head diameter of 85 and 86 nm and length of tails of 117 and 121 nm, respectively. They were characterized for optimal multiplicity of infection, the rate of adsorption to the Pcc, Pwa and Dso cells, the latent period and the burst size. The phages were genotypically characterized with RAPD-PCR and RFLP techniques. The structural proteomes of both phages were obtained by fractionation of phage proteins by SDS-PAGE. Phage protein identification was performed by liquid chromatography-mass spectrometry (LC-MS analysis. Pulsed-field gel electrophoresis (PFGE, genome sequencing and comparative genome analysis were used to gain knowledge of the length, organization and function of the ΦPD10.3 and ΦPD23.1 genomes. The potential use of ΦPD10.3 and ΦPD23.1 phages for the biocontrol of Pectobacterium spp. and Dickeya spp. infections in potato is discussed.

  12. Assessment of Interactions between Cisplatin and Two Histone Deacetylase Inhibitors in MCF7, T47D and MDA-MB-231 Human Breast Cancer Cell Lines - An Isobolographic Analysis.

    Science.gov (United States)

    Wawruszak, Anna; Luszczki, Jarogniew J; Grabarska, Aneta; Gumbarewicz, Ewelina; Dmoszynska-Graniczka, Magdalena; Polberg, Krzysztof; Stepulak, Andrzej

    2015-01-01

    Histone deacetylase inhibitors (HDIs) are promising anticancer drugs, which inhibit proliferation of a wide variety of cancer cells including breast carcinoma cells. In the present study, we investigated the influence of valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA, vorinostat), alone or in combination with cisplatin (CDDP) on proliferation, induction of apoptosis and cell cycle progression in MCF7, T47D and MDA-MB-231 human breast carcinoma cell lines. The type of interaction between HDIs and CDDP was determined by an isobolographic analysis. The isobolographic analysis is a very precise and rigorous pharmacodynamic method, to determine the presence of synergism, addition or antagonism between different drugs with using variety of fixed dose ratios. Our experiments show that the combinations of CDDP with SAHA or VPA at a fixed-ratio of 1:1 exerted additive interaction in the viability of MCF7 cells, while in T47D cells there was a tendency to synergy. In contrast, sub-additive (antagonistic) interaction was observed for the combination of CDDP with VPA in MDA-MB-231 "triple-negative" (i.e. estrogen receptor negative, progesterone receptor negative, and HER-2 negative) human breast cancer cells, whereas combination of CDDP with SAHA in the same MDA-MB-231 cell line yielded additive interaction. Additionally, combined HDIs/CDDP treatment resulted in increase in apoptosis and cell cycle arrest in all tested breast cancer cell lines in comparison with a single therapy. In conclusion, the additive interaction of CDDP with SAHA or VPA suggests that HDIs could be combined with CDDP in order to optimize treatment regimen in some human breast cancers.

  13. Assessment of Interactions between Cisplatin and Two Histone Deacetylase Inhibitors in MCF7, T47D and MDA-MB-231 Human Breast Cancer Cell Lines – An Isobolographic Analysis

    Science.gov (United States)

    Wawruszak, Anna; Luszczki, Jarogniew J.; Grabarska, Aneta; Gumbarewicz, Ewelina; Dmoszynska-Graniczka, Magdalena; Polberg, Krzysztof; Stepulak, Andrzej

    2015-01-01

    Histone deacetylase inhibitors (HDIs) are promising anticancer drugs, which inhibit proliferation of a wide variety of cancer cells including breast carcinoma cells. In the present study, we investigated the influence of valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA, vorinostat), alone or in combination with cisplatin (CDDP) on proliferation, induction of apoptosis and cell cycle progression in MCF7, T47D and MDA-MB-231 human breast carcinoma cell lines. The type of interaction between HDIs and CDDP was determined by an isobolographic analysis. The isobolographic analysis is a very precise and rigorous pharmacodynamic method, to determine the presence of synergism, addition or antagonism between different drugs with using variety of fixed dose ratios. Our experiments show that the combinations of CDDP with SAHA or VPA at a fixed-ratio of 1:1 exerted additive interaction in the viability of MCF7 cells, while in T47D cells there was a tendency to synergy. In contrast, sub-additive (antagonistic) interaction was observed for the combination of CDDP with VPA in MDA-MB-231 “triple-negative” (i.e. estrogen receptor negative, progesterone receptor negative, and HER-2 negative) human breast cancer cells, whereas combination of CDDP with SAHA in the same MDA-MB-231 cell line yielded additive interaction. Additionally, combined HDIs/CDDP treatment resulted in increase in apoptosis and cell cycle arrest in all tested breast cancer cell lines in comparison with a single therapy. In conclusion, the additive interaction of CDDP with SAHA or VPA suggests that HDIs could be combined with CDDP in order to optimize treatment regimen in some human breast cancers. PMID:26580554

  14. Assessment of Interactions between Cisplatin and Two Histone Deacetylase Inhibitors in MCF7, T47D and MDA-MB-231 Human Breast Cancer Cell Lines - An Isobolographic Analysis.

    Directory of Open Access Journals (Sweden)

    Anna Wawruszak

    Full Text Available Histone deacetylase inhibitors (HDIs are promising anticancer drugs, which inhibit proliferation of a wide variety of cancer cells including breast carcinoma cells. In the present study, we investigated the influence of valproic acid (VPA and suberoylanilide hydroxamic acid (SAHA, vorinostat, alone or in combination with cisplatin (CDDP on proliferation, induction of apoptosis and cell cycle progression in MCF7, T47D and MDA-MB-231 human breast carcinoma cell lines. The type of interaction between HDIs and CDDP was determined by an isobolographic analysis. The isobolographic analysis is a very precise and rigorous pharmacodynamic method, to determine the presence of synergism, addition or antagonism between different drugs with using variety of fixed dose ratios. Our experiments show that the combinations of CDDP with SAHA or VPA at a fixed-ratio of 1:1 exerted additive interaction in the viability of MCF7 cells, while in T47D cells there was a tendency to synergy. In contrast, sub-additive (antagonistic interaction was observed for the combination of CDDP with VPA in MDA-MB-231 "triple-negative" (i.e. estrogen receptor negative, progesterone receptor negative, and HER-2 negative human breast cancer cells, whereas combination of CDDP with SAHA in the same MDA-MB-231 cell line yielded additive interaction. Additionally, combined HDIs/CDDP treatment resulted in increase in apoptosis and cell cycle arrest in all tested breast cancer cell lines in comparison with a single therapy. In conclusion, the additive interaction of CDDP with SAHA or VPA suggests that HDIs could be combined with CDDP in order to optimize treatment regimen in some human breast cancers.

  15. Differential Ratios of Omega Fatty Acids (AA/EPA+DHA Modulate Growth, Lipid Peroxidation and Expression of Tumor Regulatory MARBPs in Breast Cancer Cell Lines MCF7 and MDA-MB-231.

    Directory of Open Access Journals (Sweden)

    Prakash P Mansara

    Full Text Available Omega 3 (n3 and Omega 6 (n6 polyunsaturated fatty acids (PUFAs have been reported to exhibit opposing roles in cancer progression. Our objective was to determine whether different ratios of n6/n3 (AA/EPA+DHA FAs could modulate the cell viability, lipid peroxidation, total cellular fatty acid composition and expression of tumor regulatory Matrix Attachment Region binding proteins (MARBPs in breast cancer cell lines and in non-cancerous, MCF10A cells. Low ratios of n6/n3 (1:2.5, 1:4, 1:5, 1:10 FA decreased the viability and growth of MDA-MB-231 and MCF7 significantly compared to the non-cancerous cells (MCF10A. Contrarily, higher n6/n3 FA (2.5:1, 4:1, 5:1, 10:1 decreased the survival of both the cancerous and non-cancerous cell types. Lower ratios of n6/n3 selectively induced LPO in the breast cancer cells whereas the higher ratios induced in both cancerous and non-cancerous cell types. Interestingly, compared to higher n6/n3 FA ratios, lower ratios increased the expression of tumor suppressor MARBP, SMAR1 and decreased the expression of tumor activator Cux/CDP in both breast cancer and non-cancerous, MCF10A cells. Low n6/n3 FAs significantly increased SMAR1 expression which resulted into activation of p21WAF1/CIP1 in MDA-MB-231 and MCF7, the increase being ratio dependent in MDA-MB-231. These results suggest that increased intake of n3 fatty acids in our diet could help both in the prevention as well as management of breast cancer.

  16. The GAPS Programme with HARPS-N at TNG . XIV. Investigating giant planet migration history via improved eccentricity and mass determination for 231 transiting planets

    Science.gov (United States)

    Bonomo, A. S.; Desidera, S.; Benatti, S.; Borsa, F.; Crespi, S.; Damasso, M.; Lanza, A. F.; Sozzetti, A.; Lodato, G.; Marzari, F.; Boccato, C.; Claudi, R. U.; Cosentino, R.; Covino, E.; Gratton, R.; Maggio, A.; Micela, G.; Molinari, E.; Pagano, I.; Piotto, G.; Poretti, E.; Smareglia, R.; Affer, L.; Biazzo, K.; Bignamini, A.; Esposito, M.; Giacobbe, P.; Hébrard, G.; Malavolta, L.; Maldonado, J.; Mancini, L.; Martinez Fiorenzano, A.; Masiero, S.; Nascimbeni, V.; Pedani, M.; Rainer, M.; Scandariato, G.

    2017-06-01

    We carried out a Bayesian homogeneous determination of the orbital parameters of 231 transiting giant planets (TGPs) that are alone or have distant companions; we employed differential evolution Markov chain Monte Carlo methods to analyse radial-velocity (RV) data from the literature and 782 new high-accuracy RVs obtained with the HARPS-N spectrograph for 45 systems over 3 years. Our work yields the largest sample of systems with a transiting giant exoplanet and coherently determined orbital, planetary, and stellar parameters. We found that the orbital parameters of TGPs in non-compact planetary systems are clearly shaped by tides raised by their host stars. Indeed, the most eccentric planets have relatively large orbital separations and/or high mass ratios, as expected from the equilibrium tide theory. This feature would be the outcome of planetary migration from highly eccentric orbits excited by planet-planet scattering, Kozai-Lidov perturbations, or secular chaos. The distribution of α = a/aR, where a and aR are the semi-major axis and the Roche limit, for well-determined circular orbits peaks at 2.5; this agrees with expectations from the high-eccentricity migration (HEM), although it might not be limited to this migration scenario. The few planets of our sample with circular orbits and α> 5 values may have migrated through disc-planet interactions instead of HEM. By comparing circularisation times with stellar ages, we found that hot Jupiters with a< 0.05 au have modified tidal quality factors 105 ≲ Q'p ≲ 109, and that stellar Q's ≳ 106 - 107 are required to explain the presence of eccentric planets at the same orbital distance. As aby-product of our analysis, we detected a non-zero eccentricity e = 0.104-0.018+0.021 for HAT-P-29; we determined that five planets that were previously regarded to be eccentric or to have hints of non-zero eccentricity, namely CoRoT-2b, CoRoT-23b, TrES-3b, HAT-P-23b, and WASP-54b, have circular orbits or undetermined

  17. Meiotic and pedigree segregation analyses in carriers of t(4;8)(p16;p23.1) differing in localization of breakpoint positions at 4p subband 4p16.3 and 4p16.1.

    Science.gov (United States)

    Midro, Alina T; Zollino, Marcella; Wiland, Ewa; Panasiuk, Barbara; Iwanowski, Piotr S; Murdolo, Marina; Śmigiel, Robert; Sąsiadek, Maria; Pilch, Jacek; Kurpisz, Maciej

    2016-02-01

    The purpose of this study was to compare meiotic segregation in sperm cells from two carriers with t(4;8)(p16;p23.1) reciprocal chromosome translocations (RCTs), differing in localization of the breakpoint positions at the 4p subband-namely, 4p16.3 (carrier 1) and 4p16.1 (carrier 2)-and to compare data of the pedigree analyses performed by direct method. Three-color fluorescent in situ hybridization (FISH) on sperm cells and FISH mapping for the evaluation of the breakpoint positions, data from pedigrees, and direct segregation analysis of the pedigrees were performed. Similar proportions of normal/balanced and unbalanced sperm cells were found in both carriers. The most common was an alternate type of segregation (about 52 % and about 48 %, respectively). Unbalanced adjacent I and adjacent II karyotypes were found in similar proportions about 15 %. The direct segregation analysis (following Stengel-Rutkowski) of the pedigree of carriers of t(4;8)(p16.1;p23.1) was performed and results were compared with the data of the pedigree segregation analysis obtained earlier through the indirect method. The probability of live-born progeny with unbalanced karyotype for carriers of t(4;8)(p16.1;p23.1) was moderately high at 18.8 %-comparable to the value obtained using the indirect method for the same carriership, which was 12 %. This was, however, markedly lower than the value of 41.2 % obtained through the pedigree segregation indirect analysis estimated for carriers of t(4;8)(p16.3;p23.1), perhaps due to the unique composition of genes present within the 4p16.1-4p 16.3 region. Revealed differences in pedigree segregation analysis did not correspond to the very similar profile of meiotic segregation patterns presented by carrier 1 and carrier 2. Most probably, such discordances may be due to differences in embryo survival rates arising from different genetic backgrounds.

  18. 多聚腺苷二磷酸核糖聚合酶抑制剂AG014699联合化疗对三阴性乳腺癌细胞株MDA-MB-231增殖的影响%Effects of Poly (ADP-ribose) Polymerase Inhibitor AG014699 Combined with Chemotherapy on the Proliferation of Triple-negative Breast Cancer Cell Line MDA-MB-231

    Institute of Scientific and Technical Information of China (English)

    孙颖; 丁焕; 黎晓晴; 黎莉

    2014-01-01

    目的 研究多聚腺苷二磷酸核糖聚合酶(PARP)抑制剂AG014699联合多西他赛(DTX)或卡铂(CBP)对三阴性乳腺癌细胞株MDA-MB-231增殖的影响,探讨PARP抑制剂AG014699联合化疗是否有协同抗肿瘤效应.方法 PARP抑制剂AG014699与DTX、CBP单独或联合作用于MDA-MB-231细胞,细胞增殖及细胞毒性实验法检测细胞增殖并用联合用药公式分析合用效应(q值0.85~1.15为单纯相加,>1.15为协同,<0.85为拮抗);流式细胞仪分析细胞凋亡及周期分布.结果 PARP抑制剂AG014699、DTX、CBP单独作用于MDA-MB-231细胞,均可抑制增殖,诱导凋亡,引起细胞周期阻滞;PARP抑制剂AG014699(10μmol/L)与DTX (10-8、10-7、10-6、10-5 mol/L)、CBP (10-5、10-4 mol/L)联合作用时,q值在0.85 ~1.15,显示相加效应;PARP抑制剂AG014699与CBP (10-3 mol/L)联合作用时,q值>1.15,显示协同效应.PARP抑制剂AG014699联合DTX或CBP能进一步促进凋亡,并使G2/M期细胞比例增加.结论 PARP抑制剂AG014699联合化疗药物DTX或CBP能显著抑制MDA-MB-231细胞增殖,发挥相加或协同抗肿瘤作用.

  19. 重庆地区231名妊娠期妇女口腔健康状况及保健行为分析%Oral health status and health behavior analysis of 231 pregnant women in Chongqing area

    Institute of Scientific and Technical Information of China (English)

    张妮; 周霞

    2012-01-01

    目的 调查重庆地区妊娠期孕妇口腔健康状况、口腔保健意识并分析其行为.方法 按照世界卫生组织制定的标准检测重庆地区231名妊娠期妇女的口腔健康状况,包括龋失补(DMFT)指数、患龋率、牙龈炎率及牙结石率,记录其口腔行为并分析.结果 重庆地区妊娠期妇女DMFT为1.4±0.9,患龋率为48.1%,牙龈炎率为57.6%,牙结石率为61.5%,且妊娠后期患龋率、牙龈炎率及牙结石率较妊娠早、中期显著增加,差异有统计学意义(P<0.05).结论 随着妊娠时间的延长,孕妇患龋率、牙龈炎率及牙结石率均增加,提示应加强孕妇口腔卫生宣传,做好口腔预防保健工作,确保母子平安.

  20. Inhibition of MMP-2-mediated cellular invasion by NF-κB inhibitor DHMEQ in 3D culture of breast carcinoma MDA-MB-231 cells: A model for early phase of metastasis.

    Science.gov (United States)

    Ukaji, Tamami; Lin, Yinzhi; Okada, Shoshiro; Umezawa, Kazuo

    2017-02-08

    The three-dimensional (3D) culture of cancer cells provides an environmental condition closely related to the condition in vivo. It would especially be an ideal model for the early phase of metastasis, including the detachment and invasion of cancer cells from the primary tumor. In one hand, dehydroxymethylepoxyquinomicin (DHMEQ), an NF-κB inhibitor, is known to inhibit cancer progression and late phase metastasis in animal experiments. In the present research, we studied the inhibitory activity on the 3D invasion of breast carcinoma cells. Breast carcinoma MDA-MB-231 cells showed the most active invasion from spheroid among the cell lines tested. DHMEQ inhibited the 3D invasion of cells at the 3D-nontoxic concentrations. The PCR array analysis using RNA isolated from the 3D on-top cultured cells indicated that matrix metalloproteinase (MMP)-2 expression is lowered by DHMEQ. Knockdown of MMP-2 and an MMP inhibitor, GM6001, both inhibited the invasion. DHMEQ was shown to inhibit the promoter activity of MMP-2 in the reporter assay. Thus, DHMEQ was shown to inhibit NF-κB/MMP-2-dependent cellular invasion in 3D-cultured MDA-MB-231 cells, suggesting that DHMEQ would inhibit the early phase of metastasis.