**3.7 PON2 and glioblastoma**

In all cancers, PON2 is overexpressed. Due to its antioxidant effect, PON-2 reduces cellular oxidative damage and influences redox signaling, which promotes cellular survival [70]. PON2 in tumor cells probably protects the intracellular membranes against oxidation and, possibly, prevents free radicals from percolating through the nuclear envelope and damaging the genetic material contained in the cells [74]. Elevated PON-2 levels may stabilize tumor cells by enhancing cellular stress resistance, attenuating mitochondrial ROS-mediated apoptosis [70].

The highest expression of PON2 is observed in liver and brain cancers. PON2 was localized in the perinuclear region. In glioblastoma, PON2 gene is amplified. The level of PON2 was a negative prognostic factor in glioblastoma [77]. Valproic acid has been shown to inhibit the growth of glioblastoma and increase the production of reactive oxygen species in glioblastoma cells. This was attributed to inhibition of PON2 by valproic acid at the transcriptional level. This deceased PON2 expression could potentiate the cytotoxic effects of ROS and enhance VPA-induced cell cycle arrest. The use of the model of transfectants overexpressing PON2 provided further support for VPA-induced GBM cell growth suppression being mediated by increased ROS production and that the effect was augmented by decreased PON2 [78].
