The Encapsulation of Febuxostat into Emulsomes Strongly Enhances the Cytotoxic Potential of the Drug on HCT 116 Colon Cancer Cells

Abstract

Febuxostat (FBX) is a drug able to inhibit xanthine oxidase and reduce uric acid production commonly used for the treatment of hyperuricemia in subjects suffering from gout. Several studies have also been directed at its use as anti-cancer drug during the last years, opening a window for its off-label use. In the present study, an optimized formulation in terms of vesicle size and drug release, obtained by encapsulation of FBX into the emulsomes (FBX-EMLs), was evaluated for its cytotoxic potential in human colorectal carcinoma (HCT 116) cells. The optimized FBX-EMLs formula had an improved half maximal inhibitory concentration (IC50), about 4-fold lower, compared to the free drug. The cell cycle analysis showed a significant inhibition of the HCT 116 cells proliferation following FBX-EMLs treatment compared to all the other conditions, with a higher number of cells accumulating on G2/M and pre-G1 phases, paralleled by a significant reduction of cells in G0/G1 and S phases. The optimized formula was also able to significantly increase the percentage of cell population in both early and late stages of apoptosis, characterized by a higher intracellular caspase-3 concentration, as well as percentage of necrotic cells. Lastly, the FBX ability to decrease the mitochondrial membrane potential was enhanced when the drug was delivered into the EMLs. In conclusion, the new formulation of FBX into EMLs improved all the parameters related to the anti-proliferative activity and the toxic potential of the drug towards colorectal cancer cells.

RETRACTED: Lipidic Nano-Sized Emulsomes Potentiates the Cytotoxic and Apoptotic Effects of Raloxifene Hydrochloride in MCF-7 Human Breast Cancer Cells: Factorial Analysis and In Vitro Anti-Tumor Activity Assessment

“…Their findings revealed that EMLs surface modification with a crystalline S-layer lattice protected cells from oxidative stress and membrane damage. Researches conducted in our laboratory have explored the utilization of EMLs in enhancing the cytotoxic and pro-apoptotic effects of statins, Piceatannol and febuxostat [ 19 , 20 , 21 , 22 ].…”

Cytotoxic and Pro-Apoptotic Effects of a Sub-Toxic Concentration of Fluvastatin on OVCAR3 Ovarian Cancer Cells After its Optimized Formulation to Melittin Nano-Conjugates

“…The analysis of cell cycle in OVCAR3 under our experimental conditions was performed by using flow cytometry as previously described ( Alfaifi et al, 2020 ; Fahmy and Aldawsari, 2020 ). Briefly, OVCAR3 cells, previously seeded in 96-well plates (3 × 10 5 cells/well), were treated with MEL, FLV-R, or FLV-MEL nano-conjugates for 24 h. Untreated cells were considered as a control.…”

“…The quantitative determination of BAX and BCL-2 proteins was carried out after 24 h treatment by using Human BAX ELISA kit (DRG Instruments GmbH, Marburg, Germany) and Zymed ® Bcl-2 ELISA Kit, respectively, according to the manufacturers’ instructions ( Fahmy and Aldawsari, 2020 ; Md et al, 2020 ). Untreated cells were considered as a control.…”

Piceatannol-Loaded Bilosome-Stabilized Zein Protein Exhibits Enhanced Cytostatic and Apoptotic Activities in Lung Cancer Cells

“…The cell cycle DNA distribution was determined using a FACS Calibur flow cytometer instrument (BD Bioscience, San Jose, CA, USA) as previously described [ 50 , 51 , 52 ]. In brief, many plates (6-well cell culture) were utilized and seeded with about 5 × 10 3 A549 cells per well.…”