Valproic acid radiosensitizes anaplastic thyroid cells through a decrease of the DNA damage repair capacity.
J Endocrinol Invest
; 46(11): 2353-2365, 2023 Nov.
Article
en En
| MEDLINE
| ID: mdl-37052871
ABSTRACT
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Tiroides
/
Carcinoma Anaplásico de Tiroides
Límite:
Humans
Idioma:
En
Revista:
J Endocrinol Invest
Año:
2023
Tipo del documento:
Article
País de afiliación:
Argentina