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

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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.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

Comisión Nacional de Energía Atómica, Gobierno de Argentina, Fondo para la Investigación Científica y Tecnológica, PICT0041, Guillermo Juvenal,Consejo Nacional de Investigaciones Científicas y Técnicas, PIP0082, Guillermo Juvenal.

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Authors and Affiliations

  1. Department of Radiobiology (CAC), National Atomic Energy Commission (CNEA), Av. General Paz 1499, B1650KNA, Buenos Aires, Argentina

    M. Perona, L. Thomasz, R. Oglio, M. A. Dagrosa & G. J. Juvenal

  2. National Scientific and Technical Research Council (CONICET), Godoy Cruz 2290, C1425FQD, CABA, Buenos Aires, Argentina

    M. Perona, L. Thomasz, C. Rosemblit, M. Campos-Haedo, M. A. Dagrosa, G. Cremaschi & G. J. Juvenal

  3. Institute of Nanosciences and Nanotechnology (INN), CNEA-CONICET, Av. General Paz 1499, B1650KNA, Buenos Aires, Argentina

    I. L. Ibañez, C. Grissi & H. A. Durán

  4. Gene Transfer Unit (UTG), Research Area, ‘Ángel H. Roffo’ Institute of Oncology of the University of Buenos Aires, Av. San Martín 5481, C1417DTB, CABA, Buenos Aires, Argentina

    M. S. Villaverde

  5. Neuroimmunomodulation and Molecular Oncology Division, Institute for Biomedical Research (BIOMED), School of Medical Sciences, Pontifical Catholic University of Argentina (UCA), Av. Alicia Moreau de Justo 1600, C1107AFF, Buenos Aires, Argentina

    C. Rosemblit, M. Campos-Haedo & G. Cremaschi

  6. School of Science and Technology, University of San Martín (UNSAM), 25 de Mayo y Francia, B1650KNA, Buenos Aires, Argentina

    H. A. Durán

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  1. M. Perona
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  2. I. L. Ibañez
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  3. L. Thomasz
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  12. G. J. Juvenal
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Correspondence to M. Perona.

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Perona, M., Ibañez, I.L., Thomasz, L. et al. Valproic acid radiosensitizes anaplastic thyroid cells through a decrease of the DNA damage repair capacity. J Endocrinol Invest 46, 2353–2365 (2023). https://doi.org/10.1007/s40618-023-02092-6

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