Alpha-tocopheryl succinate induces cytostasis and apoptosis in osteosarcoma cells: the role of E2F1

Biochem Biophys Res Commun. 2005 Jun 17;331(4):1515-21. doi: 10.1016/j.bbrc.2005.04.080.

Abstract

Alpha-tocopheryl succinate (alpha-TOS), a redox-inactive analog of vitamin E, induces cell cycle arrest, differentiation, and triggers apoptosis. We examined the ability of alpha-TOS to induce cytostasis and/or apoptosis in two human osteosarcoma cell lines, which carry wild-type pRb but differ in the p53 status. In the wt-p53 cells, alpha-TOS induced apoptosis, which was associated with p53 activation and enhanced E2F1 expression. Mutant p53 cells failed to undergo apoptosis when challenged with alpha-TOS. The cell growth arrest after alpha-TOS treatment was associated with a reduced expression of E2F1. Knocking down E2F1 rendered the alpha-TOS-sensitive cells rather resistant to the apoptotic stimulus inducing a marked and prolonged cell growth arrest. We conclude that alpha-TOS induces cell growth arrest or apoptosis involving E2F1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Cell Cycle / drug effects*
  • Cell Cycle Proteins / physiology*
  • Cell Line, Tumor
  • DNA-Binding Proteins / physiology*
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • Humans
  • Osteosarcoma / pathology*
  • Tocopherols
  • Transcription Factors / physiology*
  • Vitamin E / analogs & derivatives*
  • Vitamin E / pharmacology*

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • E2F1 protein, human
  • Transcription Factors
  • Vitamin E
  • Tocopherols