Počet záznamů: 1

Mitochondrial targeting of [alpha]-tocopheryl succinate enhances its pro-apoptotic efficacy: A new paradigm for effective cancer therapy

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    0360075 - BTO-N 2012 RIV US eng J - Článek v odborném periodiku
    Dong, L.-F. - Jameson, V.J.A. - Tilly, D. - Procházka, L. - Rohlena, Jakub - Vališ, Karel - Truksa, Jaroslav - Zobalová, Renata - Mandavian, E. - Klučková, Katarína - Stantic, M. - Štursa, Jan - Freeman, R. - Witting, P.K. - Norberg, E. - Goodwin, J. - Salvatore, B.A. - Novotná, Jana - Turánek, J. - Ledvina, Miroslav - Hozák, Pavel - Zhivotovsky, B. - Coster, M. - Ralph, S.J. - Smith, R.A.J. - Neužil, Jiří
    Mitochondrial targeting of [alpha]-tocopheryl succinate enhances its pro-apoptotic efficacy: A new paradigm for effective cancer therapy.
    Free Radical Biology and Medicine. Roč. 50, č. 11 (2011), s. 1546-1555 ISSN 0891-5849
    Grant CEP: GA ČR GA204/08/0811; GA ČR GAP301/10/1937; GA AV ČR IAA500520702; GA AV ČR KAN200520703; GA AV ČR KJB500970904; GA AV ČR KAN200100801
    Výzkumný záměr: CEZ:AV0Z50520701; CEZ:AV0Z50520514; CEZ:AV0Z4055905
    Klíčová slova: Triphenyl phosphonium * reactive oxygen species * apoptosis
    Kód oboru RIV: EB - Genetika a molekulární biologie
    Impakt faktor: 5.423, rok: 2011

    Mitochondria are emerging as intriguing targets for anti-cancer agents.We tested here a novel approach,whereby the mitochondrially targeted delivery of anti-cancer drugs is enhanced by the addition of a triphenylphosphonium group (TPP+). A mitochondrially targeted analog of vitamin E succinate (MitoVES),modified by tagging the parental compound with TPP+,induced considerably more robust apoptosis in cancer cells with a 1–2 log gain in anti-cancer activity compared to the unmodified counterpart, while maintaining selectivity for malignant cells.This is because MitoVES associates with mitochondria and causes fast generation of ROS that then trigger mitochondria-dependent apoptosis, involving transcriptional modulation of the Bcl-2 family proteins.MitoVES proved superior in suppression of experimental tumors compared to the untargeted analog. We propose that mitochondrially targeted delivery of anti-cancer agents offers a new paradigm for increasing the efficacy of anti-cancer compounds
    Trvalý link: http://hdl.handle.net/11104/0197713
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