Valproic acid radiosensitizes anaplastic thyroid cells through a decrease of the DNA damage repair capacity

PERONA, M.; IBAÑEZ, I. L.; THOMASZ, L.; VILLAVERDE, M. S.; OGLIO, R.; ROSEMBLIT, C.; GRISSI, C.; CAMPOS-HAEDO, M.; DAGROSA, M. A.; CREMASCHI, G.; DURÁN, H. A.; JUVENAL, G. J.

Journal of Endocrinological Investigation

SPRINGER

Año: 2023

AbstractBackground Anaplastic thyroid cancer (ATC) represents a rare lethal human malignancy with poor prognosis. Multimodalitytreatment, including radiotherapy, is recommended to improve local control and survival. Valproic acid (VA) is a clinicallyavailable histone deacetylase inhibitor with a well-documented side efect profle. In this study, we aim to investigate thecombined efect of VA with photon irradiation in vitro.Methods Anaplastic thyroid cancer cells (8505c) were used to investigate the radiosensitizing efect of VA.Results VA sensitized cells to photon irradiation. VA increased radiation-induced apoptosis and radiation-induced DNAdamage measured by γH2AX foci induction. Furthermore, VA prolonged γH2AX foci disappearance over time in irradiatedcells 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-inducedapoptosis and a disruption in the molecular mechanism of HR and NHEJ DNA damage repair pathways.