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

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 μg ¹⁰B 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.

Design, Synthesis, Selective Recognition Properties and Targeted Drug Delivery Application

“…[361][362][363][364][365][366][367][368] An interesting result was obtained by Perona et al using BOPP as a radiosensitizer. 369 They found that cancer cells (WRO, follicular cancer cell line) displayed approximately three times higher sensitivity for BNCT than normal control cells. Moreover, the anticancer effect was significantly improved by addition of butyric acid (an inhibitor of histone deacetylase).…”

Importance of radiobiological studies for the advancement of boron neutron capture therapy (BNCT)

“…For example, sodium butyrate, a histone deacetylase inhibitor, increased tumour boron concentration and acted as a radiosensitiser of BPA-BNCT for poorly differentiated thyroid carcinoma (Ref. 85). Photosensitisers were also explored to combine photodynamic therapy and BNCT (Refs 27, 86).…”

“…Refs83, 84). For example, sodium butyrate, a histone deacetylase inhibitor, increased tumour boron concentration and acted as a radiosensitiser of BPA-BNCT for poorly differentiated thyroid carcinoma (Ref 85…”

Closo-Carboranyl- and Metallacarboranyl [1,2,3]triazolyl-Decorated Lapatinib-Scaffold for Cancer Therapy Combining Tyrosine Kinase Inhibition and Boron Neutron Capture Therapy

“…Before each irradiation, neutron flux at the irradiation position was checked using calibrated Rh-SPND detectors in a system that mimics the configuration that will be used (96-well plates with no cells inside), while, simultaneously, signal from a boron-coated ionization chamber was used as a monitor. Based on this measurement, irradiation times were calculated in order to deliver a dose of 1 and 2 Gy with an estimated uncertainty of 10% [36]. The dosimetry, for each treatment, the time, the fluence and each dose component of the total physical absorbed dose of the neutron beam without and with boron has been studied.…”