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Food Chem Toxicol ; 95: 64-74, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27375189

RESUMO

In the course of a cytotoxicity screening of Mediterranean plants vs. neuroblastoma cells, Pistacia lentiscus was of interest. Pl-C extract, prepared from dried leaves by ultrasound assisted maceration (UAM) in chloroform, was profiled through using GC-MS techniques. To evaluate Pl-C cytotoxicity towards SH-SY5Y and SK-N-BE(2)-C cell lines, MTT, SRB and LDH assays were performed. The caspase-3 activation, DNA fragmentation, as well as micronucleation, were also evaluated. The Pl-C oxidant/antioxidant ability was estimated using different methods. The extract, rich in pentacyclic triterpenes, inhibited mitochondrial redox activity and cell viability of the tested cell lines. LDH assay established that Pl-C did not affect the cell membrane integrity. Indeed, it was able to activate caspase-3 and to cause a ladder pattern of DNA. Western blotting analysis showed that Pl-C processed caspase-3 providing two cleavage products of approximately 20 and 17-kDa, whose densitometric evaluation highlighted that Pl-C was more effective than vinblastine by 3-fold. The pro-apoptotic effect could be related to a disturbance in cell redox balance. In fact, it increased intracellular ROS production, GSSG/GSH ratio and the formation of lipoperoxidation products. The data obtained prompted to further investigate and assess the in vivo efficacy of Pl-C to prevent and/or treat neuroblastoma.


Assuntos
Apoptose/efeitos dos fármacos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Neuroblastoma/patologia , Neurônios/patologia , Pistacia/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Antioxidantes/metabolismo , Western Blotting , Caspase 3/metabolismo , Humanos , Metabolômica/métodos , Mitocôndrias/metabolismo , Neuroblastoma/tratamento farmacológico , Neuroblastoma/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Espécies Reativas de Oxigênio/metabolismo
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