RESUMEN
Combined treatment with the medicinal mushroom Ganoderma lucidum and the herb Duchesnea chrysantha extracts (GDE) causes a synergistic induction of mitochondrial damage and apoptosis in HL-60 cells. GDE treatment is selectively toxic to HL-60 leukemia cells whereas no cytotoxic effect is observed in normal peripheral blood mononuclear cells. GDE-induced apoptosis is associated with Bcl-2 down-regulation, Bax translocation, mitochondrial cytochrome c release and caspase-3 activation, suggesting that apoptosis by this combination occurs through the mitochondria-dependent pathway. The present findings suggest that this combination merits further investigation as a potential therapeutic agent for the treatment of cancer.
Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Basidiomycota/química , Mitocondrias/efectos de los fármacos , Rosaceae/química , Clorometilcetonas de Aminoácidos/farmacología , Antineoplásicos/química , Western Blotting , Caspasa 3/metabolismo , Inhibidores de Caspasas , Supervivencia Celular/efectos de los fármacos , Citocromos c/metabolismo , Relación Dosis-Respuesta a Droga , Activación Enzimática/efectos de los fármacos , Citometría de Flujo , Inhibidores de Crecimiento/química , Inhibidores de Crecimiento/farmacología , Células HL-60 , Humanos , Leucemia/metabolismo , Leucemia/patología , Mitocondrias/metabolismo , Membranas Mitocondriales/efectos de los fármacos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Transporte de Proteínas/efectos de los fármacos , Factores de Tiempo , Proteína X Asociada a bcl-2/metabolismoRESUMEN
BACKGROUND: We previously showed that an Epstein-Barr virus (EBV)-based plasmid, pEBVGFP, exerts prolonged gene expression in porcine neonatal pancreatic cell clusters (NPCCs). In this study, the mechanism underlying this was investigated. METHODS: GFP expression was analyzed in porcine cells transfected with pEBVGFP by FACS analysis and confocal microscopy. The possible integration of pEBVGFP into the chromosomal DNA was analyzed by Southern blot. Self-replication of the EBV-based plasmid in porcine cells was investigated by PCR. The NPCCs were immunostained to characterize cells transfected with pEBVGFP. RESULTS: The EBV based plasmid provided prolonged GFP expression in porcine cells and duct cells were the main cells transfected among NPCCs. Southern blot showed that the transfected pEBVGFP stayed for a long time as an episome rather than integrating into the chromosomal DNA. pEBVGFP isolated from the transfected porcine cells had methylated CpG suggesting that they self-replicated in those cells. CONCLUSIONS: The EBV-based plasmid may be useful for genetically manipulating porcine cells to enhance their value as xenotransplantation sources.