Induction of cancer cell death by apoptosis and slow release of 5-fluoracil from metal-organic frameworks Cu-BTC

• Autor(a) principal: Lucena, Flávia Raquel Santos
• Data de Publicação: 2013
• Outros Autores: Araújo, Larissa C.C. de, Rodrigues, Maria do D., Silva, Teresinha G. da, Pereira, Valéria R.A., Militão, Gardênia C.G., Fontes, Danilo A.F., Rolim-Neto, Pedro J., Silva, Fausthon F. da, Nascimento, Silene C.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da Universidade Federal do Ceará (UFC)
• Texto Completo: http://www.repositorio.ufc.br/handle/riufc/7253
• topic: Apoptose; Cancro; Morte Celular

This study aimed to evaluate the mechanism associated with cytotoxic activity displayed by the drug 5- fluorouracil incorporated in Cu-BTC MOF and its slow delivery from the Cu-BTC MOF. Structural characterization encompasses elemental analysis (CHNS), differential scanning calorimetry (DSC), thermogravimetric analysis (TG/DTG), Fournier transform infrared (FIT-IR) and X-ray diffraction (XRD) was performed to verify the process of association between the drug 5-FU and Cu-BTC MOF. Flow cytometry was done to indicate that apoptosis is the mechanism responsible for the cell death. The release profile of the drug 5-FU from Cu-BTC MOF for 48 hours was obeisant. Also, the anti-inflammatory activity was evaluated by the peritonitis testing and the production of nitric oxide and pro-inflammatory cytokines were measured. The chemical characterization of the material indicated the presence of drug associated with the coordination network in a proportion of 0.82 g 5-FU per 1.0 g of Cu-BTC MOF. The cytotoxic tests were carried out against four cell lines: NCI-H292, MCF-7, HT29 and HL60. The Cu-BTC MOF associated drug was extremely cytotoxic against the human breast cancer adenocarcinoma (MCF- 7) cell line and against human acute promyelocytic leukemia cells (HL60), cancer cells were killed by apoptosis mechanisms. The drug demonstrated a slow release profile where 82% of the drug was released in 48 hours. The results indicated that the drug incorporated in Cu-BTC MOF decreased significantly the number of leukocytes in the peritoneal cavity of rodents as well as reduced levels of cytokines and nitric oxide production.