RESUMEN
Using poly(lactic-co-glycolic) acid we developed a polymeric form of niclosamide (PFN) and investigated molecular mechanisms underlying its antitumor activity against human colorectal cancer cell lines (SW837, Caco-2, COLO 320 HSR). PFN was shown to be more cytotoxic against cancer cells and less cytotoxic against normal cells (human embryonic lung fibroblasts) as compared to niclosamide. Both niclosamide and its polymeric form caused mitochondrial damage (evaluated as a decrease in rhodamine 123 accumulation) and increased the levels of reactive oxygen species, particularly mitochondrial superoxide, resulting in the oxidative damage to biomolecules. Furthermore, niclosamide and PFN induced G0/G1 cell cycle arrest.
Asunto(s)
Antineoplásicos/farmacología , Puntos de Control del Ciclo Celular/efectos de los fármacos , Portadores de Fármacos , Mitocondrias/efectos de los fármacos , Nanopartículas/toxicidad , Niclosamida/farmacología , Resinas Acrílicas/química , Antineoplásicos/química , Células CACO-2 , Línea Celular , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Composición de Medicamentos/métodos , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Humanos , Ácido Láctico/química , Manitol/química , Mitocondrias/metabolismo , Mitocondrias/patología , Nanopartículas/química , Niclosamida/química , Especificidad de Órganos , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Alcohol Polivinílico/química , Especies Reactivas de Oxígeno/agonistas , Especies Reactivas de Oxígeno/metabolismo , Rodamina 123/metabolismoRESUMEN
The effect of nerve growth factor (NGF) on the activity and intracellular localization of protein kinase C (PKC) in pheochromocytoma PC12 cells was studied. By using immunoblotting, immunofluorescence method and phorbol ester binding, NGF was found to induce PKC translocation from the cytoplasm into the cell membrane. This process was accompanied by an increase in the protein kinase activity in the membrane fraction. Translocation was completely blocked by H-7, a protein kinase inhibitor potentiating the neurite-stimulating activity of NGF.