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

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    0369479 - BTÚ 2012 RIV US eng J - Journal Article
    Rohlena, Jakub - Dong, L.-F. - Klučková, Katarína - Zobalová, Renata - Goodwin, J. - Tilly, D. - Štursa, Jan - Pecinová, Alena - Philimonenko, Anatoly - Hozák, Pavel - Banerjee, J. - Ledvina, Miroslav - Sen, Ch.K. - Houštěk, Josef - Coster, M.J. - Neužil, Jiří
    Mitochondrially Targeted alpha-Tocopheryl Succinate Is Antiangiogenic: Potential Benefit Against Tumor Angiogenesis but Caution Against Wound Healing.
    Antioxidants & Redox Signaling. Roč. 15, č. 12 (2011), s. 2923-2935. ISSN 1523-0864. E-ISSN 1557-7716
    R&D Projects: GA MŠMT(CZ) 1M0520; GA AV ČR(CZ) KAN200520703; GA ČR(CZ) GA305/07/1008; GA ČR(CZ) GAP301/10/1937; GA ČR(CZ) GA204/08/0811
    Institutional research plan: CEZ:AV0Z50520701; CEZ:AV0Z50110509; CEZ:AV0Z4055905; CEZ:AV0Z5052915
    Keywords : Analogs of alpha-tocopheryl succinate * MitoVES * inhibition of angiogenesis
    Subject RIV: EB - Genetics ; Molecular Biology
    Impact factor: 8.456, year: 2011

    A 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.
    Permanent Link: http://hdl.handle.net/11104/0203531

     
     
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