Anticancer Effect of Fluorouracil and Gum-Based Cerium Oxide Nanoparticles on Human Malignant Colon Carcinoma Cell Line (Caco2)

We investigated whether co-incubation of 5-FU and gum-based cerium oxide nanoparticles (CeO2 NPs) would improve half-maximal inhibitory concentration (IC50) and apoptosis in the Caco-2 cancer cell line

In this experimental study, we synthesized Ceo-2-XG by the nano perception method.X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), transmission electron microscopy(TEM), dynamic light scattering (DLS) and vibrating sample magnetometer (VSM) techniques were employedto characterize the synthesized nanoparticles. The Caco-2 cancer cells were cultured and treated with Ceo-2-XG and 5-FU. Cytotoxicity analysis was carried out using MTT assay on Caco-2 cancer cells. CXCR1, CXCR2,CXCL8, BAX, BCL-2, P53, CASPASE-3, CASPASE-8 and CASPASE-9 gene expression changes were assessedby quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). The Caco-2 cancer cell mortalitymechanism was analyzed using Annexin V-FITC/PI flow cytometry. Using the inverted microscope morphologychanges of the Caco-2 cancer cells was observed.

With a sample size of roughly 11 nm, TEM analysis revealed spherical structures. Interestingly, after 72hours, 400 μg/ml nanoparticles significantly lowered the IC50 of 5-FU from 101 to 71 μg/ml (P<000.1). Furthermore,qRT-PCR analysis showed that BCL-2, CXCR1, CXCR2 and CXCR8 expressions were significantly decreased inthe 5-FU and Ceo-2-XG nanoparticles co-incubated group, compared to the 5-FU alone (P<0.001). Notably, geneexpressions of BAX, P53, CASPASE-3, CASPASE-8 and CASPASE-9 were significantly higher in the 5-FU and Ceo-2-XG nanoparticles co-incubated group, compared to the 5-FU alone (P<0.001). The findings revealed that dead cellsowing to apoptosis were more than two times higher in 5-FU and Ceo-2-XG nanoparticles cancer cells than in 5-FUalone treated cancer cells.

Co-incubation of 5-FU and Ceo-2-XG nanoparticles significantly increased apoptosis in the Caco-2cancer cells. The antiproliferative activity of co-incubated 5-FU and Ceo-2-XG nanoparticles on Caco-2 cancer cellswas substantially higher than that of 5-FU alone.