Low-dose valproic acid enhances radiosensitivity of prostate cancer through acetylated p53-dependent modulation of mitochondrial membrane potential and apoptosis.

ABSTRACT: Histone deacetylase inhibitors (HDI) have shown promise as candidate radiosensitizers for many types of cancers, including prostate cancer. However, the mechanisms of action are not well understood. In this study, we show in prostate cancer cells that valproic acid (VPA) at low concentrations has minimal cytotoxic effects yet can significantly increase radiation-induced apoptosis. VPA seems to stabilize a specific acetyl modification (lysine 120) of the p53 tumor suppressor protein, resulting in an increase in its proapoptotic function at the mitochondrial membrane. These effects of VPA are independent of any action of the p53 protein as a transcription factor in the nucleus, since these effects were also observed in native and engineered prostate cancer cells containing mutant forms of p5

SUBMITTER: Chen X 

PROVIDER: S-EPMC3655769 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature