METODO DI BELLA > NEWS > null > null > alpha-Tocopheryl succinate inhibits proliferation of mesothelioma cells by selective down-regulation of fibroblast growth factor receptors.

 
alpha-Tocopheryl succinate inhibits proliferation of mesothelioma cells by selective down-regulation of fibroblast growth factor receptors. di Stapelberg M, Tomasetti M, Alleva R, Gellert N, Procopio A, Neuzil J.
 
 
Data: 01/09/2004
Tipologia: MDB - Documentazione
Lingua: Italiano
Anno: 2004
 
 
Descrizione:
alpha-Tocopheryl succinate (alpha-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 alpha-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 alpha-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 alpha-TOS. Over-expression of E2F1, a transcriptional factor of FGFR1, but not its dominant-negative counterpart, partially blocked the inhibitory activity of alpha-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.
 
 
 
Abstract:
Fonte: Biochem Biophys Res Commun. 2004 Jun 4;318(3):636-41.
 
 
 

alpha-Tocopheryl succinate (alpha-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 alpha-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 alpha-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 alpha-TOS. Over-expression of E2F1, a transcriptional factor of FGFR1, but not its dominant-negative counterpart, partially blocked the inhibitory activity of alpha-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.

 
 
 

 

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