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Título: The classical photoactivated drug 8-methoxypsoralen and related compounds are effective without UV light irradiation against glioma cells
Autor(es): Oliveira, Diêgo Madureira de
Lima, Rute Maria Ferreira
Velozo, Jorge Clarencio de Eudes da Silva
Amorim, Ilza Alves de
Mota, Tales Henrique Andrade da
Costa, Silvia Lima
Pittella-Silva, Fabio
El-Bachá, Ramon dos Santos
Afiliação do autor: Universidade de Brasília, Faculdade UnB Ceilândia
Universidade de Brasília, Faculdade de Ciências da Saúde, Laboratório de Patologia Molecular do Câncer
Universidade Federal da Bahia,Instituto de Ciências da Saúde, Laboratório de Neuroquímica e Biologia Celular
Fiocruz, Centro de Pesquisa Gonçalo Moniz, Bahia
Escola de Medicina e Saúde Pública da Bahia
Universidade Federal da Bahia, Faculdade de Farmácia, LAPEMM
Assunto: Glioma
Medicamentos
Data de publicação: 2016
Editora: Elsevier
Referência: OLIVEIRA, Diêgo Madureira de et al. The classical photoactivated drug 8-methoxypsoralen and related compounds are effective without UV light irradiation against glioma cells. Neurochemistry International, v. 99, p. 33-41, out. 2016. DOI: https://doi.org/10.1016/j.neuint.2016.06.004.
Abstract: Currently, there is no effective therapy for high grade gliomas. 8-Methoxypsoralen (8-MOP) is a compound used in the treatment of skin diseases combined with UV light irradiation. In this work, rat glioma C6 cells, normal astrocytes and human glioblastoma GL-15 cells comprised an in vitro model to evaluate the antitumor activity of 8-MOP. We found that 8-MOP promoted a time- and concentration-dependent reduction of cell viability in tumor, but not in normal cells. This effect was more evident in log-phase growing culture, indicating antiproliferative activity, which was confirmed by colony formation assay. Long-term effect of 8-MOP at low concentration was also attested. The concentrations used in the tests (0.02–0.4 mM) were lower than plasmatic concentration found in patients. Despite the treatment leads to considerable morphological changes and apoptosis when used at high concentrations, 8-MOP did not promote cell cycle arrest, change in migration pattern neither necrosis. In addition, we evaluated the effect of 8-MOP in MDA-MB-231, CT-26 and SCC-3 cell lines, derived from other kind of primary tumors, and found that CT-26 cells did not respond to 8-MOP treatment, indicating that this compound does not act through a generic mechanism. Coumarin derivatives structurally related to 8-MOP were screened for its antitumor potential and presented different patterns of biological activity, and then it was possible to suggest the relevance of 8-MOP molecular structure for antiproliferative action. Therefore, 8-MOP, a drug with an outstanding record of safety, and related coumarins are good prototypes for development of a new class of anti-glioma drugs.
DOI: https://doi.org/10.1016/j.neuint.2016.06.004
Versão da editora: https://www.sciencedirect.com/science/article/pii/S0197018616301498?via%3Dihub
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