Inhibition of HDAC increases the senescence induced by natural polyphenols in glioma cells.

Cellular senescence is an irreversible block of cellular division, and induction of senescence is being considered for treatment of many cancer types, mainly those resistant to classical pro-apoptotic therapies. Resveratrol (Rsv) and quercetin (Quer), two natural polyphenols, are able to induce senescence in different cancer models, including gliomas, the most common and aggressive primary brain tumor. These polyphenols modulate the activity of several proteins involved in cell growth and death in cancer cells, including histone deacetylases (HDAC), but the role of HDAC in senescence induced by Rsv and Quer is unclear. The HDAC inhibitor sodium butyrate (NaB) potentiated the pro-senescent effect of Rsv and Quer in human and rat glioma cell lines but not in normal rat astrocytes. Furthermore, the increment of Quer-induced senescence by NaB was accompanied by an increase of reactive oxygen species levels and an increment of the number of cells with nuclear abnormalities. Altogether, these data support a positive role of HDAC inhibition on the senescence induced by these polyphenols, and therefore co-treatment of HDAC inhibitors and polyphenols emerges as a potential alternative for gliomas.