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Alpha-tocopheryl succinate induces DR4 and DR5 expression by a p53-dependent route: implication for sensitisation of resistant cancer cells to TRAIL apoptosis

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    0047784 - ÚMG 2007 RIV NL eng J - Journal Article
    Tomasetti, M. - Anděra, Ladislav - Alleva, R. - Borghi, B. - Neužil, Jiří - Procopio, A.
    Alpha-tocopheryl succinate induces DR4 and DR5 expression by a p53-dependent route: implication for sensitisation of resistant cancer cells to TRAIL apoptosis.
    [Alfa-tokoferol sukcinát vyvolává expresi DR4 a DR5 cestou závislou na p53: implikace pro sensitizaci rezistentních nádorových buněk k apoptóze vyvolané prostřednictvím TRAIL.]
    FEBS Letters. Roč. 580, č. 8 (2006), s. 1925-1931. ISSN 0014-5793. E-ISSN 1873-3468
    R&D Projects: GA AV ČR(CZ) IAA5052001; GA MŠMT(CZ) LN00A026
    Institutional research plan: CEZ:AV0Z50520514
    Keywords : malignant mesothelioma * TRAIL * alpha-TOS
    Subject RIV: EB - Genetics ; Molecular Biology
    Impact factor: 3.372, year: 2006

    We evaluated the ability of alpha-tocopheryl succinate (a-TOS) to sensitise TRAIL-resistant malignant mesothelioma (MM) cells to TRAIL-induced apoptosis. We show that alpha-TOS activates expression of DR4/DR5 in a p53-dependent manner and re-establishes sensitivity of resistant MM cells to TRAIL-mediated apoptosis, as documented in p53wt MM cells but not in their p53null counterparts. MM cells selected for TRAIL resistance expressed low cell surface levels of DR4 and DR5. Treatment with sub-lethal doses of a-TOS restored expression of DR4 and DR5. The ability of a-TOS to modulate expression of pro-apoptotic genes may play a role in sensitisation of tumour cells to immunological stimuli.

    Alfa-tokoferol sukcinát (vitamin E sukcinát, a-TOS) zvyšuje citlivost mesotheliomálních nádorových buněk k apoptóze indukované cytotoxickým ligandem TRAIL. a-TOS zvyšuje expresi proapoptotických TRAILových receptorů DR4/DR5 v závislosti na p53. Mesotheliomální buňky rezistentní k TRAILu mají nízkou expresi DR4/DR5, kterou lze zvýšit předinkubací se subletálními dávkami a-TOS.
    Permanent Link: http://hdl.handle.net/11104/0138589

     
     
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