*2.3.1 Valproic acid*

Recently, VPA has been shown to be an effective HDACi and has been proposed as a drug for cancer treatment [31]. VPA inhibits the proliferation of glioma cells and enhances radiosensitivity by increasing hyperacetylation in vitro and in vivo [32]. Another antitumor effect of VPA is the induction of apoptosis by the inhibition of GSK3β via the activation of Akt/ERK [33]. According to several studies, the inhibition of GSK3β suppresses survival and proliferation and induces apoptosis in human GBM cells [34]. However, some meta-analyses have revealed that the clinical benefit of VPA combination treatment in patients with GBM was contraindicated [35–39], and further studies are warranted.
