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Mitochondrially Targeted alpha-Tocopheryl Succinate Is Antiangiogenic: Potential Benefit Against Tumor Angiogenesis but Caution Against Wound Healing

  1. 1.
    SYSNO ASEP0369479
    Document TypeJ - Journal Article
    R&D Document TypeJournal Article
    Subsidiary JČlánek ve WOS
    TitleMitochondrially Targeted alpha-Tocopheryl Succinate Is Antiangiogenic: Potential Benefit Against Tumor Angiogenesis but Caution Against Wound Healing
    Author(s) Rohlena, Jakub (BTO-N) RID, ORCID
    Dong, L.-F. (AU)
    Klučková, Katarína (BTO-N) RID
    Zobalová, Renata (BTO-N) RID
    Goodwin, J. (AU)
    Tilly, D. (AU)
    Štursa, Jan (UOCHB-X)
    Pecinová, Alena (FGU-C) RID, ORCID, SAI
    Philimonenko, Anatoly (UMG-J)
    Hozák, Pavel (UMG-J) RID, ORCID
    Banerjee, J. (US)
    Ledvina, Miroslav (UOCHB-X) RID
    Sen, Ch.K. (US)
    Houštěk, Josef (FGU-C) RID, ORCID
    Coster, M.J. (AU)
    Neužil, Jiří (BTO-N) RID
    Source TitleAntioxidants & Redox Signaling. - : Mary Ann Liebert - ISSN 1523-0864
    Roč. 15, č. 12 (2011), s. 2923-2935
    Number of pages13 s.
    Languageeng - English
    CountryUS - United States
    KeywordsAnalogs of alpha-tocopheryl succinate ; MitoVES ; inhibition of angiogenesis
    Subject RIVEB - Genetics ; Molecular Biology
    R&D Projects1M0520 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
    KAN200520703 GA AV ČR - Academy of Sciences of the Czech Republic (AV ČR)
    GA305/07/1008 GA ČR - Czech Science Foundation (CSF)
    GAP301/10/1937 GA ČR - Czech Science Foundation (CSF)
    GA204/08/0811 GA ČR - Czech Science Foundation (CSF)
    CEZAV0Z50520701 - BTO-N (2007-2013)
    AV0Z50110509 - FGU-C (2005-2011)
    AV0Z4055905 - UOCHB-X
    AV0Z5052915 - UMG-J
    UT WOS000296588900002
    DOI10.1089/ars.2011.4192
    AnnotationA plausible strategy to reduce tumor progress is the inhibition of angiogenesis. We tested the antiangiogenic potential of a mitochondrially targeted analog of alpha-tocopheryl succinate (MitoVES) with high propensity to induce apoptosis. MitoVES was found to efficiently kill proliferating endothelial cells (ECs) but not contact-arrested ECs or ECs deficient in mitochondrial DNA. It suppressed angiogenesis in vitro by inducing ROS accumulation in proliferating/angiogenic ECs. Resistance of arrested ECs was ascribed to the lower mitochondrial inner transmembrane potential compared with the proliferating ECs, thus resulting in the lower level of mitochondrial uptake of MitoVES. Shorter-chain homologs of MitoVES were less efficient in angiogenesis inhibition. MitoVES was found to suppress HER2-positive breast carcinomas in a transgenic mouse as well as inhibit tumor angiogenesis. The antiangiogenic efficacy of MitoVES was corroborated by its inhibitory activity on wound healing in vivo.
    WorkplaceInstitute of Biotechnology
    ContactMonika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700
    Year of Publishing2012
Number of the records: 1  

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