DOWNREGULATION OF DNA DAMAGE REPAIR GENES BY VALPROIC ACID RADIOSENSITIZE ANAPLASTIC THYROID CANCER CELLS

PERONA, M.; GRISSI, C.; DAGROSA, M.A.; JUVENAL, G.; IBAÑEZ, I.L.; CAMPOS HAEDO, M.; CREMASCHI, G; ROSEMBLIT, C.; THOMASZ, L.; DURÁN, H.

Virtual

Congreso; Reunión conjunta SAIC.SAIC.SAAFE.NANOMED.AR; 2021

Sociedad Argentina de Investigaciones Clínicas

Introduction: Anaplastic thyroid cancer (ATC) is one of the most aggressive malignancies in humans. Novel strategies to control it, like radiotherapy as altered fractionation or in combination with chemotherapy, are therefore necessary. We have previously shown an increase in the DNA damage by the histone deacetylase inhibitors (HDACi) valproic acid (VA) in irradiated ATC cells. HDACi have emerged recently as promising anticancer agents. Their antitumor activity has been linked to their ability to induce gene expression through acetylation of histone and nonhistone proteins. DNA double-strand breaks (DSBs) are the lethal lesions induced by ionizing radiation and the majority is repaired by either non-homologous end-joining (NHEJ) or homologous recombination (HR). The modulation of DNA damage repair by HDACi could be one of the underlying mechanisms for the radiosensitizing effect in cancer cell lines.Objectives: To study the mechanism of the radiosensitizing effect of valproic acid in an anaplastic thyroid cancer cell line (8505c).Methods: Cells were incubated with 1 mM VA and irradiated with a source of gamma rays. Radiation response was analyzed by clonogenic assay. Gene expression was assessed by real time PCR at 30 min and 4 hours after irradiation.Results: A radiosensitizing effect was observed with a reduction of survival fraction at 2 Gyfrom 0.28 to 0.20 in the treated cells (p