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

Document Type : Original Article


1 Division of Cell and Molecular Biology, Department of Biology, Faculty of Science, University of Zabol, Zabol, Iran

2 Department of Physics, Faculty of Science, University of Zabol, Zabol, Iran

3 Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran


Objective: 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
Materials and Methods: 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 employed
to 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 assessed
by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). The Caco-2 cancer cell mortality
mechanism was analyzed using Annexin V-FITC/PI flow cytometry. Using the inverted microscope morphology
changes of the Caco-2 cancer cells was observed.
Results: With a sample size of roughly 11 nm, TEM analysis revealed spherical structures. Interestingly, after 72
hours, 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 in
the 5-FU and Ceo-2-XG nanoparticles co-incubated group, compared to the 5-FU alone (P<0.001). Notably, gene
expressions 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 cells
owing to apoptosis were more than two times higher in 5-FU and Ceo-2-XG nanoparticles cancer cells than in 5-FU
alone treated cancer cells.
Conclusion: Co-incubation of 5-FU and Ceo-2-XG nanoparticles significantly increased apoptosis in the Caco-2
cancer cells. The antiproliferative activity of co-incubated 5-FU and Ceo-2-XG nanoparticles on Caco-2 cancer cells
was substantially higher than that of 5-FU alone.