Valproic acid-mediated reduction of DNA double-strand break reparation capacity of irradiated MCF-7 cells

چکیده مقاله

Objectives: Histone deacetylase inhibitors (HDIs) as the 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 one of HDACs which now is effectively used in the treatment of epilepsy, migraine headaches, and some particular types of depression.
Material and Methods: In this study, we evaluated the effects of VPA and IR alone and combined on the alterations of histone H2AX phosphorylation (γH2AX) at Ser139, a markerof DNA damage and its repair, in MCF-7 breast cancer cell line. Three groups of cells were selected: 1) pretreated with VPA for 48 h followed by irradiation, 2) VPA only, and 3) irradiation only. Then the levels of γH2AX expression were evaluated using western blot.
Results: The results of our study showed that VPA enhanced the expression of γH2AX significantly, when applied 48 hours prior to irradiation compared to the IR only or VPA only treated cells. We also resulted that VPA pre-treatment, delayed γH2AX dephosphorylation and dispersal up to 12 hours after irradiation while it was disappeared just in 2 hours when using irradiation alone and without VPA pre-treatment.
Conclusion: Overall, our findings are consistent with the general consensus that VPA efficiently sensitize cancer cells to the effects of ionizing radiation and prevents DNA DSB repair, which leads to enhanced breast cancer cell death

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