Optimization of boron neutron capture therapy (BNCT) for the treatment of thyroid cancer by using the histone deacetylase inhibitor sodium butyrate

PERONA, M; RODRIGUEZ , C; CARPANO, M; NIEVAS, S; THORP, S; POZZI, E; KAHL, S; PISAREV , M; JUVENAL, G; DAGROSA, MA

Tsukuba

Congreso; 15TH International Congress on Neutron Capture Therapy; 2012

Introduction: We have shown that boron neutron capture therapy (BNCT) could be an alternative for the treatment of recurrent differentiated thyroid carcinoma (DTC). Histone deacetylase inhibitors (HDAC-I) like sodium butyrate (NaB), are agents that cause hyperacetylation of histone proteins and, as a consequence, can induce altered transcription of a number of genes. Recently we have described their capacity to increase the effect of gamma irradiation. The purpose of these studies was to evaluate the effect of the NaB as a radiosensitizer for BNCT in the treatment of DTC. Method: Human follicular thyroid carcinoma (WRO) cells were incubated with 1 mM NaB during 24 h before irradiation and then distributed into: 1) boronophenylalanine (BPA) (10 µg10B/mL) + neutrons; 2) 2, 4-bis (a,b-dihydroxyethyl)-deutero-porphyrin IX) (BOPP) (10 µg10B/mL) + neutrons; 3) Neutron beam alone. A control group without irradiation for each treatment was included. The cells were irradiated in the thermal column facility of the RA-3 reactor (flux= 1.1010 n/cm2 sec). Cell survival was evaluated with the 3-(4, 5-dimethylthiazol-2-yl)-2, 5 diphenyltetrazoliumbromide (MTT). Cell death and cell cycle distribution were evaluated 24 and 48 h post-irradiation. Results: Cell survival decreased in all the treatments as a function of the physical absorbed dose. This effect was greater in both BNCT groups. Moreover, the addition of NaB increased this effect on cell viability (p