RESUMEN
Thioredoxin reductase (TrxR), a major component of the thioredoxin system, makes a critical role in regulating cellular redox signaling and is found to be overexpressed in many human cancer cells. TrxR has become an attractive target for anticancer agents. In this work, three Ru(II) complexes with salicylate as ligand, [Ru(phen)2(SA)] (phenâ¯=â¯1,10-phenanthroline, SAâ¯=â¯salicylate, 1), [Ru(dmb)2(SA)] (dmbâ¯=â¯4,4'-dimethyl-2,2'-bipyridine, 2) and [Ru(bpy)2(SA)] (bpyâ¯=â¯2,2'-bipyridine, 3), were synthesized and characterized. The anticancer effect exerted by them was evaluated. Complex 1 was found to exhibit obvious anticancer activity, in comparison with cisplatin, against cancer cell lines, while displaying low toxicity to the normal cell line BEAS-2B. The mechanism of complex 1 cancer cell growth suppress was investigated in A549 cells. Complex 1 exerted its anticancer through inducing apoptosis and triggering cell cycle arrest at the G0/G1 phase. Complex 1 can selectively inhibit TrxR activity and thus promote the generation and accumulation of reactive oxygen species (ROS), which subsequently trigger mitochondrial dysfunction and DNA damage, activate oxidative stress-sensitive mitogen activated protein kinase (MAPK), and suppress the protein kinase B (PKB or AKT) signal pathway, resulting in apoptosis in A549 cells.
Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Complejos de Coordinación/farmacología , Especies Reactivas de Oxígeno/metabolismo , Salicilatos/farmacología , Reductasa de Tiorredoxina-Disulfuro/antagonistas & inhibidores , Antineoplásicos/síntesis química , Antineoplásicos/toxicidad , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Complejos de Coordinación/síntesis química , Complejos de Coordinación/toxicidad , Daño del ADN/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/toxicidad , Puntos de Control de la Fase G1 del Ciclo Celular/efectos de los fármacos , Humanos , Mitocondrias/metabolismo , Rutenio/química , Salicilatos/síntesis química , Salicilatos/toxicidad , Transducción de Señal/efectos de los fármacosRESUMEN
Gracilaria Gigas Harvey Polysaccharides (GHPS) were extracted with hot water and sedimentated with ethanol. The amount of polysaccharides was determined by phenol-H2SO4 method. The mineral elements and molecular configuration were analysed by inductively coupled plasma (ICP) and infrared absorption spectrum (IR). The rate of distillation was 14.98%, the amount of polysaccharides was 78.2%, and GHPS contained manifold mineral elements (Ca, Fe, Mg and S). The IR spectra manifested that the extraction was a compound of polysaccharides, i.e. acidic polysaccharides.
Asunto(s)
Gracilaria/química , Polisacáridos/química , Etanol/química , Fenol/química , Regresión Psicológica , Espectrofotometría Atómica , Espectrofotometría InfrarrojaRESUMEN
Sargassum hemiphyllum polysaccharides (SHP) was extracted by thermal water method and the physical and chemical characters, the extraction rate, contents, compositions of SHP was studied. The result showed that SHP was ashen powder, water-soluble, insoluble in organic solvents. The reaction of iodide-potassium iodide was negative to evaluate that SHP was nonstarch polysaccharides. Extraction rate was 7.04% and the content of polysaccharides was 82.9%. Ultraviolet spectrum showed that there were little DNA and protein. Infrared spectroscopy showed that SHP was main pyrano polysaccharides and had beta-linked glycopolysaccharides in molecule structure of SHP. Thin layer chromatography traced that SHP could be xylan. The results indicated that the extract was not only polysaccharides but also higher purity and the method was high efficiency.
