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

Abstract

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