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Improvement of the boron neutron capture therapy (BNCT) by the previous administration of the histone deacetylase inhibitor sodium butyrate for the treatment of thyroid carcinoma

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Abstract

We have shown that boron neutron capture therapy (BNCT) could be an alternative for the treatment of poorly differentiated thyroid carcinoma (PDTC). Histone deacetylase inhibitors (HDACI) like sodium butyrate (NaB) cause hyperacetylation of histone proteins and show capacity to increase the gamma irradiation effect. The purpose of these studies was to investigate the use of the NaB as a radiosensitizer of the BNCT for PDTC. Follicular thyroid carcinoma cells (WRO) and rat thyroid epithelial cells (FRTL-5) were incubated with 1 mM NaB and then treated with boronophenylalanine 10BPA (10 μg 10B ml−1) + neutrons, or with 2, 4-bis (α,β-dihydroxyethyl)-deutero-porphyrin IX 10BOPP (10 μg10B ml−1) + neutrons, or with a neutron beam alone. The cells were irradiated in the thermal column facility of the RA-3 reactor (flux = (1.0 ± 0.1) × 1010 n cm−2 s−1). Cell survival decreased as a function of the physical absorbed dose in both cell lines. Moreover, the addition of NaB decreased cell survival (p < 0.05) in WRO cells incubated with both boron compounds. NaB increased the percentage of necrotic and apoptotic cells in both BNCT groups (p < 0.05). An accumulation of cells in G2/M phase at 24 h was observed for all the irradiated groups and the addition of NaB increased this percentage. Biodistribution studies of BPA (350 mg kg−1 body weight) 24 h after NaB injection were performed. The in vivo studies showed that NaB treatment increases the amount of boron in the tumor at 2-h post-BPA injection (p < 0.01). We conclude that NaB could be used as a radiosensitizer for the treatment of thyroid carcinoma by BNCT.

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Acknowledgments

This work was supported by grants from the Balseiro Foundation, the National Scientific and Technical Research Council (CONICET) and the National Agency of Scientific and Technological Promotion (ANPCYT).

Conflict of interest

The authors declare that there is no conflict of interest in this paper.

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Authors and Affiliations

  1. Department of Radiobiology, National Atomic Energy Commission (CNEA), Avenida General Paz 1499, San Martín (1650), Buenos Aires, Argentina

    M. Perona, C. Rodríguez, M. Carpano, L. Thomasz, M. Pisarev, G. Juvenal & A. Dagrosa

  2. National Research Council of Argentina (CONICET), Avenida Rivadavia 1917 (1033), Ciudad Autónoma de Buenos Aires, Argentina

    L. Thomasz, M. Pisarev, G. Juvenal & A. Dagrosa

  3. Department of Boron Neutron Capture Therapy, CNEA, Avenida General Paz 1499, San Martín (1650), Buenos Aires, Argentina

    S. Nievas & M. Olivera

  4. Department of Instrumentation and Control, CNEA, Presbitero Juan Gonzalez y Aragón No 15 (1802), Ezeiza, Buenos Aires, Argentina

    S. Thorp

  5. RA-3 reactor, Research and Production Reactors, CNEA, Presbitero Juan Gonzalez y Aragón No 15 (1802), Ezeiza, Buenos Aires, Argentina

    P. Curotto & E. Pozzi

  6. Department of Pharmaceutical Chemistry, University of California, 6th Street UCSF Box 2280, Room GH-518, San Francisco, CA, 94143, USA

    S. Kahl

  7. Department of Human Biochemistry, School of Medicine, University of Buenos Aires, Paraguay 2155 (1121), Ciudad Autónoma de Buenos Aires, Argentina

    M. Pisarev

Authors
  1. M. Perona
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  2. C. Rodríguez
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  3. M. Carpano
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  4. L. Thomasz
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  5. S. Nievas
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  6. M. Olivera
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  7. S. Thorp
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  8. P. Curotto
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  9. E. Pozzi
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  10. S. Kahl
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  11. M. Pisarev
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  12. G. Juvenal
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  13. A. Dagrosa
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Corresponding authors

Correspondence to G. Juvenal or A. Dagrosa.

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A. Dagrosa and G. Juvenal should be considered as joint authors.

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Perona, M., Rodríguez, C., Carpano, M. et al. Improvement of the boron neutron capture therapy (BNCT) by the previous administration of the histone deacetylase inhibitor sodium butyrate for the treatment of thyroid carcinoma. Radiat Environ Biophys 52, 363–373 (2013). https://doi.org/10.1007/s00411-013-0470-0

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  • DOI: https://doi.org/10.1007/s00411-013-0470-0

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