The classical photoactivated drug 8-methoxypsoralen and related compounds are effective without UV light irradiation against glioma cells.
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.
Department of Biological Basis of Health Sciences, Ceilândia Campus, University of Brasilia, Federal District, Brazil; Laboratory of Molecular Pathology of Cancer, University of Brasilia, Federal District, Brazil. Electronic address: dmadureira@unb.br.
Diêgo Madureira
DM
de Oliveira
Laboratory of Neurochemistry and Cell Biology, Institute of Health Sciences, Federal University of Bahia, Bahia, Brazil.
Rute Maria
RM
Ferreira Lima
Gonçalo Moniz Research Center - Fiocruz, Bahia, Brazil; School of Medicine and Public Health of Bahia, Bahia, Brazil.
Jorge
J
Clarencio
LAPEMM, Faculty of Pharmacy, Federal University of Bahia, Bahia, Brazil.
Eudes da Silva
EDS
Velozo
LAPEMM, Faculty of Pharmacy, Federal University of Bahia, Bahia, Brazil.
Ilza Alves
IA
de Amorim
School of Pharmacy, Ceilândia Campus, University of Brasilia, Federal District, Brazil.
Tales Henrique
TH
Andrade da Mota
Laboratory of Neurochemistry and Cell Biology, Institute of Health Sciences, Federal University of Bahia, Bahia, Brazil.
Silvia Lima
SL
Costa
Laboratory of Molecular Pathology of Cancer, University of Brasilia, Federal District, Brazil.
Fábio Pittella
FP
Silva
Laboratory of Neurochemistry and Cell Biology, Institute of Health Sciences, Federal University of Bahia, Bahia, Brazil.
Ramon Dos Santos
RDS
El-Bachá
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005910:Glioma / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D008730:Methoxsalen / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D014466:Ultraviolet Rays
D017319:Photosensitizing Agents; D008730:Methoxsalen
7-Methoxycoumarin (PubChem CID: 10748); 8-methoxypsoralen; Coumarin (PubChem CID: 323); Coumarins; Coumurrayin (PubChem CID: 176911); Glioma; Methoxsalen (PubChem CID: 4114); Osthole (PubChem CID: 10228); Psoralen; Psoralen (PubChem CID: 6199); Trioxsalen (PubChem CID: 5585)