Bio-Effects of TiO2 Nanoparticles on Human Colorectal Cancer and Umbilical Vein Endothelial Cell Lines

Document Type: Research Articles

Authors

1 Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.

2 Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran.

3 Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

4 Department of Biology, Faculty of Exact and Natural Sciences, Ivane Javakhishvili Tbilisi State University, Georgia.

5 Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.

6 Neuroscience Research Center, Urmia University of Medical Sciences, Urmia, Iran.

Abstract

Background: Due to the possible biomedical potential of nanoparticles, titanium dioxide nanoparticles (TiO2 NPs)
have received great attention in cancer research. Although selectivity of cytotoxicity with TiO2 NPs in various cells is
clinically significant comparisons of cancer and non-cancer cells have been limited. Therefore, we here studied exposure
to TiO2 NPs in colorectal cancer cells (CRCs) and human umbilical vein endothelial cells (HUVECs). Methods: After
characterization of TiO2 NPs, culture and treatment of cells (HCT116, HT29 and HUVEC), viability was assessed by
MTT assay and in terms of morphological features. Acridine orange (AO) and propidium iodide (PI) assays were carried
out to estimate the incidence of apoptosis. The RT-PCR method was also employed to evaluate the expression of P53,
Bax, Bcl-2 and Caspase 3. Results: Exposure to increasing concentrations of TiO2 NPs enhanced overall cell survival
of HCT116 cells and reduced the Bcl-2 and Caspase 3 expression while the ratio of Bax/Bcl-2 was down-regulated.
TiO2 NPs at 400 and 50 μg/ml concentrations suppressed cell proliferation and induced apoptosis of HT29 cells and
also up-regulated P53 and Bax at the mRNA level, enhanced the Bax/Bcl-2 ratio and eventually up-regulated Caspase
3 mRNA. Although, inhibition of cell proliferation in HUVECs was seen at 200 and 400 μg/ml TiO2 NPs, it was not
marked. Conclusion: TiO2 NPs have selective bio-effects on exposed cells with dose- and cell-dependent influence on
viability. Cell proliferation in HCT116 as a metastatic colorectal cancer cell line appeared to be stimulated via multiple
signaling pathways, with promotion of apoptosis in less metastatic cells at 50 and 400 μg/ml concentrations. This was
associated with elevated P53, Bax and Caspase 3 mRNA and reduced Bcl-2 expression. However, TiO2 NPs did not
exert any apparent significant effects on HUVECs as hyperproliferative angiogenic cells.

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