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

• Published in: Biomedicine & pharmacotherapy Vol. 67; no. 8; pp. 707 - 713
• Main Authors: Lucena, Flávia Raquel Santos, de Araújo, Larissa C.C, Rodrigues, Maria do D, da Silva, Teresinha G, Pereira, Valéria R.A, Militão, Gardênia C.G, Fontes, Danilo A.F, Rolim-Neto, Pedro J, da Silva, Fausthon F, Nascimento, Silene C
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.10.2013
• Subjects: 5-fluorouracil; Animals; Anti-inflammatory and cytotoxic activities; Antimetabolites, Antineoplastic - administration & dosage; Antimetabolites, Antineoplastic - pharmacology; Apoptosis; Apoptosis - drug effects; Cell Line, Tumor; Cell Survival - drug effects; Copper - chemistry; Cu-BTC MOF; Delayed-Action Preparations; Drug Carriers - chemistry; Female; Fluorouracil - administration & dosage; Fluorouracil - pharmacology; Humans; Internal Medicine; Medical Education; Mice; Organometallic Compounds - chemistry; Slow release; Tricarboxylic Acids - chemistry; 5-fluorouracil; Slow release; Cu-BTC MOF; Anti-inflammatory and cytotoxic activities; Apoptosis
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2013.06.003

Abstract 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.