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

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• 作者：Fl谩via Raquel Santos Lucena ; Larissa C.C. de Ara煤jo ; Maria do D. Rodrigues ; Teresinha G. da Silva ; Val茅ria R.A. Pereira ; Gard锚nia C.G. Milit茫o ; Danilo A.F. Fontes ; Pedro J. Rolim-Neto ; Fausthon F. da Silva ; Silene C. Nascimento
• 关键词：Cu-BTC MOF ; 5-fluorouracil ; Apoptosis ; Anti-inflammatory and cytotoxic activities ; Slow release
• 刊名：Biomedicine and Pharmacotherapy
• 出版年：October, 2013
• 年：2013
• 卷：67
• 期：8
• 页码：707-713
• 全文大小：1101 K

文摘

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.