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

0369479 - BTÚ 2012 RIV US eng J - Článek v odborném periodiku
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
Grant CEP: 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
Výzkumný záměr: CEZ:AV0Z50520701; CEZ:AV0Z50110509; CEZ:AV0Z4055905; CEZ:AV0Z5052915
Klíčová slova: Analogs of alpha-tocopheryl succinate * MitoVES * inhibition of angiogenesis
Kód oboru RIV: EB - Genetika a molekulární biologie
Impakt faktor: 8.456, rok: 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.
Trvalý link: http://hdl.handle.net/11104/0203531