Document Type : Original Paper
Biochemistry and Metabolic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran
Biochemistry and biophysics dept of Golestan university of medical sciences.Faculty of Medicine, Golestan University of Medical Sciences.Begin of Shast colah road.Gorgan .Iran
Laboratory Sciences Research Center, Golestan University of Medical Sciences, Gorgan, Iran
H istone deacetylase inhibitors (HDIs), as radiation sensitizing agents, are considered as a novel class of anti-cancer factors, which are studied in various tumor cell-lines. Valproic acid (VPA) is an HDI, which is effectively used in the treatment of epilepsy, migraines, and some particular types of depression. In this study, we evaluated the effects of VPA and ionizing radiation separately, as well as combined, with the alterations of histone H2AX phosphorylation (γH2AX) at Ser139, a marker of DNA damage and its repair, on MCF-7 breast cancer cell line.
Materials and Methods
Three groups of cells were selected, including 1) pretreated with VPA for 48 h followed by irradiation, 2) VPA only, and 3) irradiation only. The levels of γH2AX expression were evaluated using Western blot.
The results of our study showed that VPA significantly enhanced the expression of γH2AX, when applied 48 h prior to irradiation compared to the IR or VPA only treated cells. We also concluded that VPA pre-treatment delayed γH2AX dephosphorylation and dispersal for up to 12 h after irradiation, while γH2AX dephosphorylation disappeared in just 2 h when using irradiation alone and without VPA pre-treatment.
Our findings are consistent with the general consensus that VPA efficiently sensitizes cancer cells to the effects of ionizing radiation and prevents DNA double-strand break repair, which leads to enhanced breast cancer cell death.