Por favor, use este identificador para citar o enlazar este ítem: http://repositorio.ufc.br/handle/riufc/7216
Tipo: Artigo de Periódico
Título : Inhibition of DNA topoisomerase I activity and induction of apoptosis by thiazacridine derivatives
Autor : Barros, Francisco W.A.
Bezerra, Daniel P.
Ferreira, Paulo M. P.
Cavalcanti, Bruno C.
Silva, Teresinha G.
Pitta, Marina G. R.
Lima, Maria do C. A. de
Galdino, Suely L.
Pitta, Ivan da R.
Costa-Lotufo, Letícia V.
Moraes Filho, Manoel Odorico de
Burbano, Rommel R.
Guecheva, Temenouga N.
Henriques, João A. P.
Pessoa, Cláudia
Palabras clave : Apoptose;DNA Topoisomerases Tipo I
Fecha de publicación : abr-2013
Editorial : Toxicology and Applied Pharmacology
Citación : BARROS, F. W. A. et al. Inhibition of DNA topoisomerase I activity and induction of apoptosis by thiazacridine derivatives. Toxicology and Applied Pharmacology, San Diego, Calif., v. 268, n. 1, p. 37-46, abr. 2013.
Abstract: Thiazacridine derivatives (ATZD) are a novel class of cytotoxic agents that combine an acridine and thiazolidine nucleus. In this study, the cytotoxic action of four ATZD were tested in human colon carcinoma HCT-8 cells: (5Z)-5-acridin-9-ylmethylene-3-(4-methylbenzyl)-thiazolidine-2,4-dione — AC-4; (5ZE)-5-acridin-9- ylmethylene-3-(4-bromo-benzyl)-thiazolidine-2,4-dione — AC-7; (5Z)-5-(acridin-9-ylmethylene)-3-(4-chlorobenzyl)- 1,3-thiazolidine-2,4-dione — AC-10; and (5ZE)-5-(acridin-9-ylmethylene)-3-(4-fluoro-benzyl)-1,3- thiazolidine-2,4-dione — AC-23. All of the ATZD tested reduced the proliferation of HCT-8 cells in a concentration- and time-dependent manner. There were significant increases in internucleosomal DNA fragmentation without affecting membrane integrity. For morphological analyses, hematoxylin–eosin and acridine orange/ethidium bromide were used to stain HCT-8 cells treated with ATZD, which presented the typical hallmarks of apoptosis. ATZD also inducedmitochondrial depolarisation and phosphatidylserine exposure and increased the activation of caspases 3/7 in HCT-8 cells, suggesting that this apoptotic cell death was caspase-dependent. In an assay using Saccharomyces cerevisiae mutants with defects in DNA topoisomerases 1 and 3, the ATZD showed enhanced activity, suggesting an interaction between ATZD and DNA topoisomerase enzyme activity. In addition, ATZD inhibited DNA topoisomerase I action in a cell-free system. Interestingly, these ATZD did not cause genotoxicity or inhibit the telomerase activity in human lymphocyte cultures at the experimental levels tested. In conclusion, the ATZD inhibited the DNA topoisomerase I activity and induced tumour cell death through apoptotic pathways.
URI : http://www.repositorio.ufc.br/handle/riufc/7216
ISSN : 1096-0333 On line
0041-008X Impresso
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