Selenium nanoparticles (Se NPs) attract a lot of attention as potential cancer therapeutic agents. However, the antitumor activities of pure Se NPs are poor, and some modifiers are needed to enhance the activities. In the present study, we prepared Ferulic Acid (FA)-modified selenium nanoparticles in a facile synthetic approach. The obtained FA-Se NPs were characterized using transmission electron microscope (TEM), dynamic light scattering (DLS), ultraviolet-visible spectrophotometer (UV-VIS), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and Energy dispersive X-ray (EDX) spectroscopy. In vitro antitumor effects of FA, Se NPs and FA-Se NPs in HepG-2 cells were examined by methyl thiazolyl tetrazolium (MTT) assay. It showed that FA-Se NPs effectively inhibited the growth of HepG-2 cells with IC50 value of 11.57 ± 3.6 μg/ml, while the value of Se NPs was >100 μg/ml. In addition, FA behaves no obvious antitumor effects at high concentrations up to 100 μg/ml. In order to investigate the antitumor mechanism of FA-Se NPs, fluorescence morphological examination and Annexin V-FITC/PI staining analysis were performed to observe the apoptosis of HepG-2 cells induced by FA-Se NPs. Meanwhile, mitochondrial membrane potential (MMP), intracellular reactive oxygen species (ROS) levels and caspase-3 and -9 activities were detected. The results revealed that FA-Se NPs induced intracellular ROS generation and MMP disruption by finally activating caspase-3/9 to trigger HepG-2 cells apoptosis through mitochondrial pathway. Further investigation on the interactions of FA-Se NPs with calf thymus DNA (ctDNA) indicated that the antitumor activities may be associated with the DNA-binding properties of FA-Se NPs.
Keywords: Apoptosis; DNA-binding; Ferulic acid; Mitochondrial pathway; Selenium nanoparticles.
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