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1.
Int J Biol Macromol ; 137: 829-835, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31284007

RESUMO

Selenium nanoparticles (SeNPs) have been attracting increasing attention as potential cancer therapeutic agents. In the present study, laminarin polysaccharides (LP) decorated selenium nanoparticles (LP-SeNPs) with an average diameter of ca. 60 nm were synthesized. Transmission electron microscope (TEM), laser particle analyzer, UV-visible spectrometer and Energy dispersive X-ray (EDX) spectrometer were applied to characterize the prepared SeNPs. The cytotoxicity, apoptosis, and autophagy were examined using a series of cellular assays. The results revealed that LP-SeNPs exhibited cytotoxicity against HepG2 cells with IC50 value was 23.4 ±â€¯2.7 µM. After cells were treated with various concentrations of LP-SeNPs (10, 20 and 40 µM) for 24h, the total apoptosis rate increased to 17.4 ±â€¯1.6, 20.9 ±â€¯1.3 and 30.9 ±â€¯1.2%, respectively. Additionally, treatment of LP-SeNPs increased the expression of Bax and cleaved caspase-9 but decreased the level of Bcl-2. This suggested that LP-SeNPs induced mitochondria-mediated apoptosis. Further, exposure of cells to LP-SeNPs for 12 h induced the upregulation of LC3-II and p62. Treatment of chloroquine (CQ), the inhibitors of the autophagosome, resulted in further accumulation of p62 and LC3-II. These results demonstrated that LP-SeNPs induced the activation of early autophagy, but blocked the late phase of autophagy. Inhibition of late phase of autophagy resulted in the damaged organelles cannot be cleared and aggravating apoptosis. In conclusion, these results indicated that LP-SeNPs exerted its cytotoxicity in HepG2 cells by inhibiting autophagy and inducing apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Glucanos/química , Glucanos/farmacologia , Nanopartículas/química , Selênio/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Células Hep G2 , Humanos , Transdução de Sinais/efeitos dos fármacos , Soluções
2.
Pharm Biol ; 56(1): 528-534, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30387372

RESUMO

CONTEXT: Selenium nanoparticles (SeNPs) have attracted worldwide attention due to their unique properties and potential bioactivities. Considering that hawthorn is both a traditional medicine and a common edible food, hawthorn fruit extract (HE) was chosen as a reductant to prepare SeNPs. OBJECTIVE: SeNPs were synthesized by using an aqueous HE as a reductant and stabilizer. The antitumor activities and potential mechanisms of SeNPs were explored by using a series of cellular assays. MATERIALS AND METHODS: The HE mediated SeNPs (HE-SeNPs) were examined using various characterisation methods. The cytotoxicity was measured against HepG2 cells after treated with 0, 5, 10 and 20 µg/mL of HE-SeNPs for 24 h. Annexin V-FITC/PI staining analysis was performed to observe the apoptosis of HepG2 cells. Additionally, mitochondrial membrane potential (MMP), intracellular reactive oxygen species (ROS) levels were evaluated. Finally, the protein expression levels of caspase-9 and Bcl-2 were identified by Western blot. RESULTS: The mono-dispersed and stable SeNPs were prepared with an average size of 113 nm. HE-SeNPs showed obvious antitumor activities towards HepG2 cells with an IC50 of 19.22 ± 5.3 µg/mL. Results from flow cytometry revealed that both early and total apoptosis rates increased after treating with HE-SeNPs. After cells were treated with various concentrations of HE-SeNPs (5, 10 and 20 µg/mL) for 24 h, the total rate increased to 7.3 ± 0.5, 9.7 ± 1.7 and 19.2 ± 1.6%, respectively. Meanwhile, treatment of HE-SeNPs up-regulated intracellular ROS levels and reduced the MMP. In addition, HE-SeNPs induced the up-regulation of caspase-9 and down-regulation of Bcl-2. DISCUSSION AND CONCLUSIONS: HE-SeNPs induced intracellular oxidative stress and mitochondrial dysfunction to initiate HepG2 cell apoptosis through the mitochondrial pathway. Therefore, HE-SeNPs may be a candidate for further evaluation as a chemotherapeutic agent for human liver cancer.


Assuntos
Apoptose/efeitos dos fármacos , Crataegus/química , Nanopartículas/química , Selênio/química , Selênio/farmacologia , Caspase 9/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Frutas/química , Química Verde , Células Hep G2 , Humanos , Fígado/citologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Nanopartículas/administração & dosagem , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo
3.
Mater Sci Eng C Mater Biol Appl ; 90: 104-112, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-29853073

RESUMO

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 ±â€¯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.


Assuntos
Ácidos Cumáricos/química , Nanopartículas/química , Selênio/química , Células Hep G2 , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Microscopia Eletrônica de Transmissão , Mitocôndrias/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Selênio/farmacologia , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
4.
Artigo em Inglês | MEDLINE | ID: mdl-24109864

RESUMO

The methods of dominant frequency and Lorenz plot are used in this study to evaluate the activation rate and the activation rate variability of cardiac signals during atrial fibrillation. An epicardial mapping system was applied to acquire the atrial electrogram of mongrel dogs. The dominant frequency and Lorenz plot of each signal from various myocardial regions of the atria were analyzed. Our results show that both a frequency gradient and a variability gradient exist in the atria and the roots of pulmonary veins. The dominant frequencies of the anterior atria are higher than the posterior ones and the activation variability of both atria was higher than those of the pulmonary veins. A combination of these two methods may provide a more comprehensive understanding of the electrophysiology mechanism associated with atrial fibrillation.


Assuntos
Algoritmos , Técnicas Eletrofisiológicas Cardíacas/métodos , Mapeamento Epicárdico/métodos , Animais , Fibrilação Atrial/fisiopatologia , Cães , Análise de Fourier
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