RESUMEN
The purpose of this study was to investigate the anti-cancer effect of melittin on growth, migration, invasion, and apoptosis of non-small-cell lung cancer (NSCLC) cells. This study also explored the potential anti-cancer mechanism of melittin in NSCLC cells. The results demonstrated that melittin suppressed growth, migration, and invasion, and induced apoptosis of NSCLC cells in vitro. Melittin increased pro-apoptotic caspase-3 and Apaf-1 gene expression. Melittin inhibited tumor growth factor (TGF)-β expression and phosphorylated ERK/total ERK (pERK/tERK) in NSCLC cells. However, TGF-β overexpression (pTGF-β) abolished melittin-decreased TGF-β expression and pERK/tERK in NSCLC cells. Treatment with melittin suppressed tumor growth and prolonged mouse survival during the 120-day observation in vivo. Treatment with melittin increased TUNEL-positive cells and decreased expression levels of TGF-β and ERK in tumor tissue compared to the control group. In conclusion, the findings of this study indicated that melittin inhibited growth, migration, and invasion, and induced apoptosis of NSCLC cells through down-regulation of TGF-β-mediated ERK signaling pathway, suggesting melittin may be a promising anti-cancer agent for NSCLC therapy.
Asunto(s)
Animales , Conejos , Apoptosis , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Sistema de Señalización de MAP Quinasas , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamiento farmacológico , Meliteno/farmacología , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Movimiento Celular , Factor de Crecimiento Transformador beta/metabolismo , Línea Celular Tumoral , Caspasa 3 , Factor Apoptótico 1 Activador de Proteasas , Invasividad NeoplásicaRESUMEN
The purpose of this study was to investigate the anti-cancer effect of melittin on growth, migration, invasion, and apoptosis of non-small-cell lung cancer (NSCLC) cells. This study also explored the potential anti-cancer mechanism of melittin in NSCLC cells. The results demonstrated that melittin suppressed growth, migration, and invasion, and induced apoptosis of NSCLC cells in vitro. Melittin increased pro-apoptotic caspase-3 and Apaf-1 gene expression. Melittin inhibited tumor growth factor (TGF)-ß expression and phosphorylated ERK/total ERK (pERK/tERK) in NSCLC cells. However, TGF-ß overexpression (pTGF-ß) abolished melittin-decreased TGF-ß expression and pERK/tERK in NSCLC cells. Treatment with melittin suppressed tumor growth and prolonged mouse survival during the 120-day observation in vivo. Treatment with melittin increased TUNEL-positive cells and decreased expression levels of TGF-ß and ERK in tumor tissue compared to the control group. In conclusion, the findings of this study indicated that melittin inhibited growth, migration, and invasion, and induced apoptosis of NSCLC cells through down-regulation of TGF-ß-mediated ERK signaling pathway, suggesting melittin may be a promising anti-cancer agent for NSCLC therapy.
Asunto(s)
Apoptosis , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Sistema de Señalización de MAP Quinasas , Meliteno/farmacología , Animales , Factor Apoptótico 1 Activador de Proteasas , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Caspasa 3 , Línea Celular Tumoral , Movimiento Celular , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Ratones , Invasividad Neoplásica , Factor de Crecimiento Transformador beta/metabolismoAsunto(s)
Granuloma de Células Plasmáticas/diagnóstico , Hepatopatías/diagnóstico , Biopsia , Diagnóstico Diferencial , Femenino , Granuloma de Células Plasmáticas/diagnóstico por imagen , Granuloma de Células Plasmáticas/patología , Humanos , Hepatopatías/diagnóstico por imagen , Hepatopatías/patología , Pruebas de Función Hepática , Imagen por Resonancia Magnética , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones , Valor Predictivo de las Pruebas , Remisión Espontánea , Factores de TiempoRESUMEN
DNA from a region downstream of and overlapping the polyketide synthase (PKS) gene cluster for jadomycin B biosynthesis in Streptomyces venezuelae was cloned and sequenced. Analysis of the nucleotide sequence located one complete ORF (ORF6), an incomplete one representing the 3' region of ORF4 in the PKS cluster, and a second incomplete one (ORF7). The deduced amino acid sequences for ORFs 6 and 7 resemble those of oxygenases. Since a plausible biosynthetic pathway for jadomycin B includes an angular polyketide intermediate that undergoes oxidative ring fission before condensation with an amino acid, we subcloned one of the presumptive oxygenase genes (ORF6) in a segregationally unstable shuttle vector (pHJL400) and disrupted it by inserting the gene for apramycin resistance. Transformation of S. venezuelae with the disruption vector and selection for apramycin resistance gave mutants blocked in jadomycin biosynthesis. Southern hybridization confirmed that gene replacement had occurred. Cultures of the mutants accumulated a metabolite identified by comparison with an authentic sample as rabelomycin, a non-nitrogenous polyketide-derived antibiotic originally isolated from Streptomyces olivaceus.