title: Apoptosis through Bcl-2/Bax and cleaved caspase up-regulation in melanoma treated by boron neutron capture therapy.
abstract: Boron neutron capture therapy (BNCT) is a binary treatment involving selective accumulation of boron carriers in a tumor followed by irradiation with a thermal or epithermal neutron beam. The neutron capture reaction with a boron-10 nucleus yields high linear energy transfer (LET) particles, alpha and (7)Li, with a range of 5 to 9 µm. These particles can only travel very short distances and release their damaging energy directly into the cells containing the boron compound. We aimed to evaluate proliferation, apoptosis and extracellular matrix (ECM) modifications of B16F10 melanoma and normal human melanocytes after BNCT. The amounts of soluble collagen and Hsp47, indicating collagen synthesis in the ECM, as well as the cellular markers of apoptosis, were investigated. BNCT decreased proliferation, altered the ECM by decreasing collagen synthesis and induced apoptosis by regulating Bcl-2/Bax in melanoma. Additionally, BNCT also increased the levels of TNF receptor and the cleaved caspases 3, 7, 8 and 9 in melanoma. These results suggest that multiple pathways related to cell death and cell cycle arrest are involved in the treatment of melanoma by BNCT.
authors.affiliation: Laboratory of Biochemistry and Biophysics, Butantan Institute, São Paulo, Brazil.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Faião-Flores
authors.forename: Paulo Rogério Pinto
authors.initials: PR
authors.lastname: Coelho
authors.forename: João Dias
authors.initials: JD
authors.lastname: Toledo Arruda-Neto
authors.forename: Silvya Stuchi
authors.initials: SS
authors.lastname: Maria-Engler
authors.forename: Manoela
authors.initials: M
authors.lastname: Tiago
authors.forename: Vera Luiza
authors.initials: VL
authors.lastname: Capelozzi
authors.forename: Ricardo Rodrigues
authors.initials: RR
authors.lastname: Giorgi
authors.forename: Durvanei Augusto
authors.initials: DA
authors.lastname: Maria
mesh_terms: D000704:Analysis of Variance; D017209:Apoptosis / Q000502:physiology* / Q000528:radiation effects; D015153:Blotting, Western; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D003094:Collagen / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D005109:Extracellular Matrix / Q000378:metabolism / Q000528:radiation effects; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D050958:HSP47 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D018499:Linear Energy Transfer / Q000502:physiology* / Q000528:radiation effects; D008544:Melanocytes; D008546:Melanoma, Experimental / Q000532:radiotherapy*; D046529:Microscopy, Electron, Transmission; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D017931:DNA Primers; D050958:HSP47 Heat-Shock Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018124:Receptors, Tumor Necrosis Factor; C494660:SERPINH1 protein, human; D051028:bcl-2-Associated X Protein; D003094:Collagen; D020169:Caspases