Cell type-specific anti-cancer properties of valproic acid: independent effects on HDAC activity and Erk1/2 phosphorylation.
In: BMC Cancer, Jg. 10 (2010), S. 383-394
Online
academicJournal
Zugriff:
Background: The anti-epileptic drug valproic acid (VPA) has attracted attention as an anti-cancer agent. Methods: The present study investigated effects of VPA exposure on histone deacetylase (HDAC) inhibition, cell growth, cell speed, and the degree of Erk½ phosphorylation in 10 cell lines (BT4C, BT4Cn, U87MG, N2a, PC12-E2, CSML0, CSML100, HeLa, L929, Swiss 3T3). Results: VPA induced significant histone deacetylase (HDAC) inhibition in most of the cell lines, but the degree of inhibition was highly cell type-specific. Moreover, cell growth, motility and the degree of Erk½ phosphorylation were inhibited, activated, or unaffected by VPA in a cell type-specific manner. Importantly, no relationship was found between the effects of VPA on HDAC inhibition and changes in the degree of Erk½ phosphorylation, cell growth, or motility. In contrast, VPA-induced modulation of the MAPK pathway downstream of Ras but upstream of MEK (i.e., at the level of Raf) was important for changes in cell speed. Conclusions: These results suggest that VPA can modulate the degree of Erk½ phosphorylation in a manner unrelated to HDAC inhibition and emphasize that changes in the degree of Erk½ phosphorylation are also important for the anti-cancer properties of VPA. [ABSTRACT FROM AUTHOR]
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Cell type-specific anti-cancer properties of valproic acid: independent effects on HDAC activity and Erk1/2 phosphorylation.
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Autor/in / Beteiligte Person: | Gotfryd, Kamil ; Skladchikova, Galina ; Lepekhin, Eugene A. ; Berezin, Vladimir ; Bock, Elisabeth ; Walmod, Peter S. |
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Zeitschrift: | BMC Cancer, Jg. 10 (2010), S. 383-394 |
Veröffentlichung: | 2010 |
Medientyp: | academicJournal |
ISSN: | 1471-2407 (print) |
DOI: | 10.1186/1471-2407-10-383 |
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