Valproic Acid Radiosensitizes Anaplastic Thyroid Cells Through a Decrease of the DNA Damage Repair Capacity
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Background: Anaplastic thyroid cancer (ATC) represents a rare lethal human malignancy with poor prognosis. Multimodality treatment, including radiotherapy, is recommended to improve local control and survival. Valproic acid (VA) is a clinically available histone deacetylase inhibitor with a well-documented side effect profile. In this study, we aim to investigate the combined effect of VA with photon irradiation in vitro.
Methods: Anaplastic thyroid cancer cells (8505c) were used to investigate the radiosensitizing effect of VA.
Results: VA sensitized cells to photon irradiation. VA increased radiation-induced apoptosis and radiation-induced DNA damage measured by γH2AX foci induction. Furthermore, VA prolonged γH2AX foci disappearance over time in irradiated cells and decreased the radiation-induced levels of mRNA of key DNA damage repair proteins of the homologous recombination (HR) and the nonhomologous end joining (NHEJ) pathways.
Conclusions: VA at a clinically safe dose enhance the radiosensitivity of 8505c cells through an increase in radiation-induced apoptosis and a disruption in the molecular mechanism of HR and NHEJ DNA damage repair pathways.
Liu J, Yu Y, Xu B, Liang Q, Fang T, Zhou N Am J Transl Res. 2025; 16(12):7317-7329.
PMID: 39822534 PMC: 11733373. DOI: 10.62347/EAFU3015.