RESUMO
Arsenic trioxide (As2O3) inhibits cell growth and induces apoptosis in certain types of cancer cells including acute promyelocytic leukemia, prostate and ovarian carcinomas, but its effect on response of tumor cells to ionizing radiation has never been explored before. Here we demonstrate that As2O3 can sensitize human cervical cancer cells to ionizing radiation both in vitro and in vivo. As2O3 in combination with ionizing radiation have a synergistic effect in decreasing clonogenic survival and in the regression of established human cervical tumor xenografts. Pretreatment of the cells with As2O3 also synergistically enhanced radiation-induced apoptosis. Apoptosis of the cells by combined treatment of As2O3 and radiation was associated with reactive oxygen species generation and loss of mitochondrial membrane potential, resulting in the activation of caspase-9 and caspase-3. The combined treatment also resulted in an increased G2/M cell cycle distribution at the concentration of As2O3 which did not alter cell cycle when applied alone. These results indicate that As2O3 can synergistically enhance radiosensitivity of human cervix carcinoma cells in vitro and in vivo, suggesting a potential clinical applicability of combination treatment of As2O3 and ionizing radiation in cancer therapies.
Assuntos
Arsenicais/farmacologia , Carcinoma/terapia , Terapia Combinada/métodos , Óxidos/farmacologia , Radiossensibilizantes/farmacologia , Neoplasias do Colo do Útero/terapia , Animais , Trióxido de Arsênio , Arsenicais/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Relação Dose-Resposta a Droga , Relação Dose-Resposta à Radiação , Avaliação Pré-Clínica de Medicamentos , Feminino , Células HeLa , Humanos , Camundongos , Camundongos Nus , Transplante de Neoplasias , Óxidos/uso terapêutico , Radiossensibilizantes/uso terapêutico , Resultado do Tratamento , Ensaio Tumoral de Célula-Tronco , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Arsenic trioxide (As2O3) can induce clinical remission in patients with acute promyelocytic leukemia (APL) through induction of apoptosis. To investigate the potential therapeutic usage of As2O3 in cervical cancer and its possible mechanisms, human cervical cancer cell line HeLa was employed. The cells underwent apoptosis in response to As2O3, accompanied by a decrease of mitochondrial membrane potential and caspase-3 activation. Overexpression of Bcl-2, however, prevented the dissipation of mitochondrial membrane potential, subsequently protecting the cells from As2O3-induced apoptosis. As2O3 increased cellular content of reactive oxygen species (ROS), especially hydrogen peroxide (H2O2), and the antioxidant N-acetyl-L-cysteine completely suppressed As2O3-induced apoptosis. Furthermore, incubation of the cells with catalase resulted in significant suppression of As2O3-induced apoptosis. The above results indicate that the induction of HeLa cell apoptosis by As2O3 involved an early decrease in cellular mitochondrial membrane potential and increase in ROS content, predominantly H2O2, followed by caspase-3 activation and DNA fragmentation.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Arsenicais/farmacologia , Caspases/metabolismo , Células HeLa/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Óxidos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Acetilcisteína/farmacologia , Antioxidantes/farmacologia , Trióxido de Arsênio , Catalase/farmacologia , Relação Dose-Resposta a Droga , Ativação Enzimática , Células HeLa/metabolismo , Células HeLa/patologia , Humanos , Peróxido de Hidrogênio/metabolismo , Potenciais da Membrana/efeitos dos fármacos , Mitocôndrias/fisiologiaRESUMO
Electrorheological (ER) effects of alginic acid and alginate salts (Na(+) alginate, NH(4)(+) alginate, and Ca(2+) alginate) dispersed suspensions were investigated under DC electric fields. A noteworthy result is that the Ca(2+) alginate dispersed suspension showed negative electrorheological effects under electric fields while the other suspensions exhibited positive electrorheological effects. It is the first time that the negative ER effect is obtained with the biomacromolecule. Interestingly, at the DC electric fields, the electromigration of particles to two electrodes was observed in the negative ER fluid, while the particles-bridges formed between two electrodes in the case of the positive ER fluid. In conclusion, the specific salt type of biomacromolecules could be suitable ER particles for negative ER suspension. We believe that our study can present a new way for the development of the biocompatible and eco-friendly negative ER fluids.
RESUMO
Herein, we demonstrate the adsorption process system with the diethylenetriamne coupled polyacrylonitrile fiber for the removal of Cu(II) and Cr(VI) ions in the aqueous solution. The synthesized chelating fiber showed a high adsorption capacity of 11.4 mequiv/g. Interestingly, the crystal growth of copper ions on the chelating fiber was observed during the adsorption process. The chelating fiber packed column showed the high performance of the removal of Cu(II) in the aqueous solution due to the distinct characteristic of the crystal growth of metal ions on the chelating fiber. After Cu(II) adsorption on the chelating fiber, the color of the fiber changed to light blue from yellow. The isotherm parameter n of 1.991 was obtained with Freundlich isotherm model for the adsorption equilibrium study which indicates that Cu(II) adsorption on the chelating fiber is very favorable due to n>1. The pseudo-first-order and pseudo-second-order model equations were used for the kinetic study.
Assuntos
Quelantes/química , Cromo/isolamento & purificação , Cobre/isolamento & purificação , Água/química , Adsorção , Cinética , Espectroscopia de Ressonância Magnética , Microscopia Eletrônica de Varredura , Soluções , Espectroscopia de Infravermelho com Transformada de Fourier , TermodinâmicaRESUMO
Different-sized particles dispersed electrorheological (ER) fluids were fabricated with poly(acryloamidino diethylenediamine) to observe the influence of the particle size on ER behaviors. The fine particles dispersed ER suspension showed stable shear stress under a DC electric field. On the other hand, the rough particles dispersed suspension showed trembling shear stress which is divided into four regions in a plot of shear stress against shear rate. Our suggested spring-damper model equation treated the wide range of shear rate and specific (trembling) behaviors of shear stress in ER fluids. In this study, we successfully obtained various ER fluids showing different behaviors just by changing the size of particles in the ER fluids. All of the curves of the shear stress plotted against shear rate were fitted well by our spring-damper model.