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

Authors:   M. Perona,C. Rodríguez,M. Carpano,L. Thomasz,S. Nievas,M. Olivera,S. Thorp,P. Curotto,E. Pozzi,S. Kahl,M. Pisarev,G. Juvenal,A. Dagrosa
Journal: Radiation and Environmental Biophysics
https://doi.org/10.1007/s00411-013-0470-0
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 $mu$g 10B ml-1) + neutrons, or with 2, 4-bis ($alpha$,$beta$-dihydroxyethyl)-deutero-porphyrin IX 10BOPP (10 $mu$g10B 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. {textcopyright} 2013 Springer-Verlag Berlin Heidelberg.