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https://www.arca.fiocruz.br/handle/icict/16531
THE CLASSICAL PHOTOACTIVATED DRUG 8-METHOXYPSORALEN AND RELATED COMPOUNDS ARE EFFECTIVE WITHOUT UV LIGHT IRRADIATION AGAINST GLIOMA CELLS
Author
Affilliation
University of Brasilia. Department of Biological Basis of Health Sciences. Brasília, DF, Brasil / University of Brasilia. Laboratory of Molecular Pathology of Cancer. Brasília, DF, Brasil
Federal University of Bahia. Institute of Health Sciences. Laboratory of Neurochemistry and Cell Biology. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / School of Medicine. Public Health of Bahia. Salvador, BA, Brasil
Federal University of Bahia. Faculty of Pharmacy. LAPEMM. Salvador, BA, Brasil
Federal University of Bahia. Faculty of Pharmacy. LAPEMM. Salvador, BA, Brasil
University of Brasilia. School of Pharmacy. Ceilândia, DF, Brasil
Federal University of Bahia. Institute of Health Sciences. Laboratory of Neurochemistry and Cell Biology. Salvador, BA, Brasil
University of Brasilia. Laboratory of Molecular Pathology of Cancer. Brasília, DF, Brasil
Federal University of Bahia. Institute of Health Sciences. Laboratory of Neurochemistry and Cell Biology. Salvador, BA, Brasil
Federal University of Bahia. Institute of Health Sciences. Laboratory of Neurochemistry and Cell Biology. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / School of Medicine. Public Health of Bahia. Salvador, BA, Brasil
Federal University of Bahia. Faculty of Pharmacy. LAPEMM. Salvador, BA, Brasil
Federal University of Bahia. Faculty of Pharmacy. LAPEMM. Salvador, BA, Brasil
University of Brasilia. School of Pharmacy. Ceilândia, DF, Brasil
Federal University of Bahia. Institute of Health Sciences. Laboratory of Neurochemistry and Cell Biology. Salvador, BA, Brasil
University of Brasilia. Laboratory of Molecular Pathology of Cancer. Brasília, DF, Brasil
Federal University of Bahia. Institute of Health Sciences. Laboratory of Neurochemistry and Cell Biology. Salvador, BA, Brasil
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.
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