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Bio-Effects of TiO2 Nanoparticles on Human Colorectal Cancer and Umbilical Vein Endothelial Cell Lines
Authors:Nasim Rahmani Kukia1Yousef Rasmi1   2Ardashir Abbasi3Nana Koshoridze4Alireza Shirpoor5Giorgi Burjanadze4Ehsan Saboory6
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 isclinically significant comparisons of cancer and non-cancer cells have been limited. Therefore, we here studied exposureto TiO2 NPs in colorectal cancer cells (CRCs) and human umbilical vein endothelial cells (HUVECs). Methods: Aftercharacterization of TiO2 NPs, culture and treatment of cells (HCT116, HT29 and HUVEC), viability was assessed byMTT assay and in terms of morphological features. Acridine orange (AO) and propidium iodide (PI) assays were carriedout 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 survivalof 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 andalso up-regulated P53 and Bax at the mRNA level, enhanced the Bax/Bcl-2 ratio and eventually up-regulated Caspase3 mRNA. Although, inhibition of cell proliferation in HUVECs was seen at 200 and 400 μg/ml TiO2 NPs, it was notmarked. Conclusion: TiO2 NPs have selective bio-effects on exposed cells with dose- and cell-dependent influence onviability. Cell proliferation in HCT116 as a metastatic colorectal cancer cell line appeared to be stimulated via multiplesignaling pathways, with promotion of apoptosis in less metastatic cells at 50 and 400 μg/ml concentrations. This wasassociated with elevated P53, Bax and Caspase 3 mRNA and reduced Bcl-2 expression. However, TiO2 NPs did notexert any apparent significant effects on HUVECs as hyperproliferative angiogenic cells.
Keywords:Colorectal cancer cells  HUVEC  TiO2 NPs  Cytotoxicity  Apoptosis
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