Tocopherol-associated protein-1 accelerates apoptosis induced by alpha-tocopheryl succinate in mesothelioma cells

Biochem Biophys Res Commun. 2006 May 19;343(4):1113-7. doi: 10.1016/j.bbrc.2006.03.052. Epub 2006 Mar 31.

Abstract

Alpha-tocopheryl succinate (alpha-TOS), a redox-silent analogue of vitamin E, induces apoptosis in multiple cell lines in a selective manner, by activating the intrinsic pathway. Since it is a highly hydrophobic compound, it may require a carrier protein for its trafficking to intracellular targets like mitochondria. We studied the role of the ubiquitous tocopherol-associated protein-1 (TAP1 or sec14-like 2) in apoptosis induction by alpha-TOS in malignant mesothelioma (MM) cells. Over-expression of TAP1 in MM cells sensitised them to apoptosis by low doses of alpha-TOS which were sub-apoptotic for the parental cells. Apoptosis induced in TAP1-over-expressing cells was mitochondria- and caspase-dependent, as suggested by dissipation of mitochondrial trans-membrane potential and inhibition by zVAD-fmk, respectively. Binding assays showed affinity of alpha-TOS for TAP1. Finally, TAP1 over-expressing cells accumulated alpha-TOS at higher levels compared to their normal counterparts. We suggest that TAP1 may act as an intracellular shuttle for alpha-TOS, promoting apoptosis initiated by this vitamin E analogue, as shown here for MM cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Carrier Proteins / physiology*
  • Caspases / metabolism
  • Cell Line, Tumor
  • Humans
  • Lipoproteins / physiology*
  • Membrane Potentials
  • Mesothelioma / metabolism
  • Mesothelioma / pathology*
  • Mitochondria / physiology
  • Tocopherols
  • Trans-Activators / physiology*
  • Vitamin E / analogs & derivatives*
  • Vitamin E / pharmacology

Substances

  • Antineoplastic Agents
  • Carrier Proteins
  • Lipoproteins
  • SEC14L2 protein, human
  • Trans-Activators
  • Vitamin E
  • Caspases
  • Tocopherols