Valproic acid radiosensitize anaplastic thyroid cancer cells through a decrease of the reparation capacity at low doses of radiation

ROSEMBLIT, C; PERONA, M.; PISAREV, M; GRISSI, C.; DURÁN, H.; IBAÑEZ, I. L.; CREMASCHI, G; JUVENAL, G

Virtual

Congreso; Reunión de Sociedades de Biociencias 2020, LXV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC), LXVIII Reunión Anual de la Sociedad Argentina de Inmunología (SAI), Reunión Anual de la Sociedad Argentina de Fisiología (SAFIS); 2020

SAIC, SAI, SAFIS

Introduction: Histone deacetylase (HDAC) inhibitors have emerged recently as promising anticancer agents. The antitumor activity of HDAC inhibitors has been linked to their ability to induce gene expression through acetylation of histone and nonhistone proteins. Anaplastic thyroid cancer (ATC) is a rare and aggressive malignancy. Radiotherapy (RT) is one of the main modalities of treatment for ATC. In most patients, surgical resection is not possible. Therefore, RT either as altered fractionation or in combination with chemotherapy has an important role in achieving local control. Objectives: The objective was to study the radiosensitizing effect of valproic acid at different radiation doses in an anaplastic thyroid cancer cell line (8505c). Methods: Cells were incubated with 1 mM VA and irradiated with a source of gamma rays at different doses. Radiation response was analyzed by clonogenic assay. Cell cycle and cell death were measured 24 and 48 h after irradiation at 2 and 5 Gy. DNA damage was evaluated 30 min and 24 h after irradiation at 2 and 5 Gy. Ku80 expression was assessed by Western Blot. Results: A radiosensitizing effect was observed with a reduction of survival fraction at 2 Gy from 0.28 to 0.20 in the treated cells (p