RESUMO
In this study, we extracted a polysaccharide (short-chain polysaccharide [PS]) from porcine cartilage and examined its function in chronic myeloid leukaemia by using human K562 cells and mouse L1210 cells. Results of cell proliferation assay indicated that PS inhibited cancer cell growth at different concentrations, while it had little effect on normal cells. The presence of morphological aspects of apoptosis, such as nuclear shrinkage, was shown in H&E stained sections. The occurrence of PS-induced apoptosis was confirmed by TUNEL assay and cell cycle analysis. The results of immunofluorescent staining indicated the molecular mechanism underlying. Through interfering with the cell cycle of tumor cells, PS may induce apoptosis by downregulating the expression level of cyclin D1 and upregulating the level of p21 protein. Correlation analysis of apoptosis and MAPK suggested that inactivation of ERK was crucial for PS induced apoptosis, while JNK phosphorylation had a small effect and p38 was not involved. In vivo assay showed that PS inhibited L1210 cell growth in vivo and prolonged the life span of L1210-bearing mice. We conclude that PS is a polysaccharide with anticancer effects and induced apoptosis in human K562 cells.
Assuntos
Apoptose/efeitos dos fármacos , Cartilagem/química , Polissacarídeos/farmacologia , Animais , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ciclina D1/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Imunofluorescência , Humanos , Marcação In Situ das Extremidades Cortadas , Células K562 , Masculino , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Células NIH 3T3 , Polissacarídeos/isolamento & purificação , Coloração e Rotulagem , SuínosRESUMO
We calculate the distribution of interparticle normal forces P(F) near the glass and jamming transitions in model supercooled liquids and foams, respectively. P(F) develops a peak that appears near the glass or jamming transitions, whose height increases with decreasing temperature, decreasing shear stress and increasing packing density. A similar shape of P(F) was observed in experiments on static granular packings. We propose that the appearance of this peak signals the development of a yield stress. The sensitivity of the peak to temperature, shear stress, and density lends credence to the recently proposed generalized jamming phase diagram.