α-Tocopheryl succinate inhibits proliferation of mesothelioma cells by selective down-regulation of fibroblast growth factor receptors

Michael Stapelberg, Marco Tomasetti, Renata Alleva, Nina Gellert, Antonio Procopio, Jiri Neuzil

Research output: Contribution to journalArticle

Abstract

α-Tocopheryl succinate (α-TOS), a redox-silent analogue of vitamin E, inhibits malignant mesotheliomas (MM) in a pre-clinical model. Here we investigated the underlying mechanism. Exposure of MM cells to α-TOS triggered apoptosis at higher and inhibited proliferation at lower concentrations, while this effect was not observed in non-malignant mesothelial cells. Sub-apoptotic doses of α-TOS caused down-regulation of fibroblast growth factor receptor-1 (FGFR1) selectively in MM cells, while the effect on FGFR2 was only marginal. FGF1 and FGF2 enhanced MM cell proliferation that was suppressed by α-TOS. Over-expression of E2F1, a transcriptional factor of FGFR1, but not its dominant-negative counterpart, partially blocked the inhibitory activity of α-TOS on MM cell proliferation. Our data suggest a novel mechanism by which a clinically intriguing agent selectively suppresses proliferation of cancer cells, as shown here for the untreatable mesotheliomas.

Original languageEnglish
Pages (from-to)636-641
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume318
Issue number3
DOIs
Publication statusPublished - Jun 4 2004

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Keywords

  • Apoptosis
  • FGF receptor signalling
  • Proliferation
  • Vitamin E succinate

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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