α-Tocopheryl succinate induces DR4 and DR5 expression by a p53-dependent route: Implication for sensitisation of resistant cancer cells to TRAIL apoptosis

Marco Tomasetti, Ladislav Andera, Renata Alleva, Battista Borghi, Jiri Neuzil, Antonio Procopio

Research output: Contribution to journalArticle

Abstract

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 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 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.

Original languageEnglish
Pages (from-to)1925-1931
Number of pages7
JournalFEBS Letters
Volume580
Issue number8
DOIs
Publication statusPublished - Apr 3 2006

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Keywords

  • α-TOS
  • DR4
  • DR5
  • Malignant mesothelioma
  • p53
  • TRAIL

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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