title: Cell cycle arrest, extracellular matrix changes and intrinsic apoptosis in human melanoma cells are induced by Boron Neutron Capture Therapy.
abstract: Boron Neutron Capture Therapy (BNCT) involves the selective accumulation of boron carriers in tumor tissue followed by irradiation with a thermal or epithermal neutron beam. This therapy is therefore a cellular irradiation suited to treat tumors that have infiltrated into healthy tissues. BNCT has been used clinically to treat patients with cutaneous melanomas which have a high mortality. Human normal melanocytes and melanoma cells were treated with BNCT at different boronophenylalanine concentrations for signaling pathways analysis. BNCT induced few morphological alterations in normal melanocytes, with a negligible increase in free radical production. Melanoma cells treated with BNCT showed significant extracellular matrix (ECM) changes and a significant cyclin D1 decrease, suggesting cell death by necrosis and apoptosis and cell cycle arrest, respectively. BNCT also induced a significant increase in cleaved caspase-3 and a decrease in the mitochondrial electrical potential with selectivity for melanoma cells. Normal melanocytes had no significant differences due to BNCT treatment, confirming the data from the literature regarding the selectivity of BNCT. The results from this study suggest that some signaling pathways are involved in human melanoma treatment by BNCT, such as cell cycle arrest, ECM changes and intrinsic apoptosis.
authors: Laboratory of Biochemistry and Biophysics, Butantan Institute, São Paulo, Brazil. fernandafaiao@yahoo.com.br
authors: Fernanda
authors: F
authors: Faião-Flores
authors: Paulo Rogério Pinto
authors: PR
authors: Coelho
authors: João Dias Toledo
authors: JD
authors: Arruda-Neto
authors: Silvya Stuchi
authors: SS
authors: Maria-Engler
authors: Durvanei Augusto
authors: DA
authors: Maria
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D016754:Boron Neutron Capture Therapy / Q000009:adverse effects*; D053148:Caspase 3 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000528:radiation effects; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D008297:Male; D008544:Melanocytes / Q000378:metabolism / Q000528:radiation effects*; D008545:Melanoma / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D053078:Membrane Potential, Mitochondrial / Q000528:radiation effects; D009336:Necrosis / Q000139:chemically induced
chemical_list: D005609:Free Radicals; D003094:Collagen; D053148:Caspase 3