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

M Perona1,2, I L Ibañez3, L Thomasz4,5

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

Journal of Endocrinological Investigation
|April 13, 2023
PubMed
Summary
This summary is machine-generated.

Valproic acid (VA) enhances anaplastic thyroid cancer cell radiosensitivity by increasing apoptosis and disrupting DNA repair pathways. This combination therapy shows promise for improving outcomes in this lethal malignancy.

Keywords:
Anaplastic thyroid cancerApoptosisDNA damage responseHistone deacetylase inhibitorsRadiosensitivityValproic acid

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Area of Science:

  • Oncology
  • Molecular Biology
  • Radiotherapy

Background:

  • Anaplastic thyroid cancer (ATC) is a rare, aggressive malignancy with a poor prognosis.
  • Multimodality treatment, including radiotherapy, is crucial for local control and survival in ATC.
  • Valproic acid (VA), a histone deacetylase inhibitor, has a known safety profile and is being investigated for its potential in cancer therapy.

Purpose of the Study:

  • To investigate the combined effect of valproic acid (VA) and photon irradiation on anaplastic thyroid cancer cells in vitro.
  • To determine if VA can enhance the radiosensitivity of ATC cells.

Main Methods:

  • Anaplastic thyroid cancer cell line (8505c) was utilized for in vitro experiments.
  • Cells were treated with VA and exposed to photon irradiation.
  • Radiosensitizing effects were assessed by measuring apoptosis, DNA damage (γH2AX foci), and the expression of DNA repair proteins.

Main Results:

  • Valproic acid (VA) significantly sensitized anaplastic thyroid cancer cells to photon irradiation.
  • VA increased radiation-induced apoptosis and DNA damage, evidenced by elevated γH2AX foci.
  • VA prolonged the persistence of DNA damage and decreased the expression of key DNA repair proteins involved in homologous recombination (HR) and nonhomologous end joining (NHEJ) pathways.

Conclusions:

  • Valproic acid (VA), at a clinically safe dose, enhances the radiosensitivity of anaplastic thyroid cancer cells.
  • This radiosensitization is attributed to increased radiation-induced apoptosis and impaired DNA damage repair mechanisms (HR and NHEJ).
  • The findings suggest a potential therapeutic strategy combining VA with radiotherapy for ATC treatment.