The histone deacetylase inhibitor PCI-24781 as a putative radiosensitizer in pediatric glioblastoma cell lines

Autor(es)

de Andrade, Pamela Viani ^[1] ; Andrade, Augusto Faria ^[2] ; de Paula Queiroz, Rosane Gomes ^[1] ; Scrideli, Carlos Alberto ^[1] ; Tone, Luiz Gonzaga ^{[1, 2]} ; Valera, Elvis Terci ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Pediat, Ribeirao Preto Med Sch, Hosp Clin, Fac Med Ribeirao Preto, 7 Andar, Ave Bandeirantes 3900, BR-14048900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Dept Genet, Ribeirao Preto Med Sch, Ave Bandeirantes 3900, BR-14048900 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: CANCER CELL INTERNATIONAL; v. 16, APR 18 2016.
• Citações Web of Science: 1

Resumo

Background: Glioblastoma (GBM) is considered to be one of the most aggressive tumors of the central nervous system (CNS). Even with the use of modern treatment protocols, the prognosis remains reserved, with children with GBM having a mean survival of 12-15 months. Methods: In the present study we investigated the potential radiosensitizing effect of PCI-24781, a potent panhistone deacetylase inhibitor (HDACi), on the SF188 and KNS42 cell lines of pediatric GBM. Cell proliferation rates, clonogenicity and apoptosis were compared in the presence and absence of treatment with PCI-24781. We also compared the clonogenicity rates of the irradiated SF188 and KNS42 cell lines with or without previous treatment with PCI-24781 at the doses of 0.25-16 mu M. In addition, we investigated the effects of PCI-24781 on the expression of some of the main proteins responsible for the repair of double-strand DNA breaks caused by irradiation. Results: The inhibitor blocked cell proliferation, induced death by apoptosis and reduced the colony forming capacity of the cell lines, both of them showing a significant decrease of colony formation at all irradiation doses. The expression of the Rad51 protein, important for the homologous recombination (HR) repair pathway, and of the DNA-PKcs, Ku70 and Ku86 proteins, important for the non-homologous end joining (NHEJ) repair pathway, was more reduced when the irradiated cell line was previously treated with PCI-24781 than when it was treated exclusively with radiotherapy. Conclusions: These findings demonstrate that HDACi PCI-24781 has a radiosensitizing profile that compromises the repair of double-strand DNA breaks in cells of pediatric GBM treated with radiotherapy. (AU)

• Processo FAPESP: 13/15891-8 - Inibidor de histona desacetilase (HDACi) como possível radiosensibilizante em linhagem celular de glioblastoma pediátrico
• Beneficiário: Elvis Terci Valera
• Modalidade de apoio: Auxílio à Pesquisa - Regular