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α‐Tocopheryl succinate induces DR4 and DR5 expression by a p53‐dependent route: Implication for sensitisation of resistant cancer cells to TRAIL apoptosis
Author(s) -
Tomasetti Marco,
Andera Ladislav,
Alleva Renata,
Borghi Battista,
Neuzil Jiri,
Procopio Antonio
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.02.054
Subject(s) - apoptosis , chemistry , cancer cell , cancer research , cell , null cell , microbiology and biotechnology , gene , biology , cancer , biochemistry , genetics
We evaluated the ability of α‐tocopheryl succinate (α‐TOS) to sensitise TRAIL‐resistant malignant mesothelioma (MM) cells to TRAIL‐induced apoptosis. We show that α‐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 p53 wt MM cells but not in their p53 null counterparts. MM cells selected for TRAIL resistance expressed low cell surface levels of DR4 and DR5. Treatment with sub‐lethal doses of α‐TOS restored expression of DR4 and DR5. The ability of α‐TOS to modulate expression of pro‐apoptotic genes may play a role in sensitisation of tumour cells to immunological stimuli.