Alpha-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

doi:10.1016/j.febslet.2006.02.054

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

FEBS Lett. 2006 Apr 3;580(8):1925-31. doi: 10.1016/j.febslet.2006.02.054. Epub 2006 Feb 28.

Authors

Marco Tomasetti¹, Ladislav Andera, Renata Alleva, Battista Borghi, Jiri Neuzil, Antonio Procopio

Affiliation

¹ Department of Molecular Pathology and Innovative Therapies, Polytechnic University of Marche, via Ranieri 1, Ancona, Italy. mtomasetti@virgilio.it

PMID: 16529749
DOI: 10.1016/j.febslet.2006.02.054

Abstract

We evaluated the ability of alpha-tocopheryl succinate (alpha-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 alpha-TOS restored expression of DR4 and DR5. The ability of alpha-TOS to modulate expression of pro-apoptotic genes may play a role in sensitisation of tumour cells to immunological stimuli.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis / drug effects*
Apoptosis Regulatory Proteins / pharmacology*
Cytoplasm / metabolism
Drug Resistance, Neoplasm / drug effects*
Humans
Membrane Glycoproteins / pharmacology*
Neoplasms / metabolism
Neoplasms / pathology
Receptors, Cell Surface / metabolism
Receptors, TNF-Related Apoptosis-Inducing Ligand
Receptors, Tumor Necrosis Factor / metabolism*
Recombinant Proteins / metabolism
TNF-Related Apoptosis-Inducing Ligand
Tocopherols
Tumor Cells, Cultured
Tumor Necrosis Factor-alpha / pharmacology*
Tumor Suppressor Protein p53 / metabolism*
Vitamin E / analogs & derivatives*
Vitamin E / pharmacology

Substances

Apoptosis Regulatory Proteins
Membrane Glycoproteins
Receptors, Cell Surface
Receptors, TNF-Related Apoptosis-Inducing Ligand
Receptors, Tumor Necrosis Factor
Recombinant Proteins
TNF-Related Apoptosis-Inducing Ligand
TNFRSF10A protein, human
TNFRSF10B protein, human
TNFSF10 protein, human
Tumor Necrosis Factor-alpha
Tumor Suppressor Protein p53
Vitamin E
Tocopherols