Nano-TiO2 regulates the MAPK (ERK, P38) pathway to promote apoptosis and inhibit proliferation of human colon cells

Abstract

BackgroundNano titanium dioxides (TiO2) are widely used in drug development, food additives and packaging materials. Although several studies have demonstrated the poisonousness of TiO2 in vivo and in vitro, the underlying molecular mechanisms have not been fully revealed. MethodsCharacterization of TiO2 by FTIR, XRD, TEM and DLS. The NCM460 cell line, representing normal colon epithelial cells, was utilized as a model to assess the impact of TiO2 nanoparticles (TiO2-NPs) on cell proliferation and apoptosis. The potential molecular mechanisms underlying its toxic effects were investigated through transcriptome analysis, RT-qPCR, and western blot experiments. ResultsThe particle size of the TiO2-NPs used is about 25 nm, which has typical characteristics of anatase. TiO2-NPs at a concentration of 30–60 μg/mL will cause changes in colon cell morphology, decreased proliferation ability, and increased number of apoptotic cells. TiO2-NPs at a concentration of 6 μg/mL did not significantly modify the transcriptome expression profile of colon cells; while 30 μg/mL had a significant effect, leading to up-regulation of gene expression. The differentially expressed genes predominantly modulate the MAPK signaling pathway, TNF signaling pathway, cytokine-cytokine receptor interaction, and other related pathways. Further, western blot analysis revealed that higher concentrations of TiO2-NPs (30–60 μg/mL) could up-regulate the expression of P53, P21 and Bax, while down-regulating the expression of Bcl2 by regulating the MAPK (ERK, P38) signaling pathway. Simultaneously, it also promoted the decreased in Fos protein expression and inhibited the phosphorylation of Jun and Fos. ConclusionThis study demonstrates that TiO2-NPs may exert potential toxic effects on colon cells, and therefore the intake of TiO2-NPs should be strictly regulated in practical applications.