Ruta graveolens L. Induces Death of Glioblastoma Cells and Neural Progenitors, but Not of Neurons, via ERK 1/2 and AKT Activation

摘要: Glioblastoma multiforme is a highly aggressive brain tumor whose prognosis very poor. Due to early invasion of parenchyma, its complete surgical removal nearly impossible, and even after combined treatment (association surgery chemo- radio-therapy) five-year survival only about 10%. Natural products are sources novel compounds endowed with therapeutic properties in many human diseases, including cancer. Here, we report that the water extract Ruta graveolens L., commonly known as rue, induces death different glioblastoma cell lines (U87MG, C6 U138) widely used test drugs preclinical studies. graveolens’ effect was mediated by ERK1/2 AKT activation, inhibition these pathways, via PD98058 wortmannin, reverted antiproliferative activity. Rue also affects neural precursor cells (A1) obtained from embryonic mouse CNS. As case glioma cells, rue stimulates activation A1 whereas their blockade pharmacological inhibitors prevents death. Interestingly, upon induction differentiation cycle exit, become resistant rue’s noxious effects but not those temozolomide cisplatin, two alkylating agents therapy. Finally, rutin, major component extract, failed cause death, suggesting rutin itself responsible for observed effects. In conclusion, extracts induce discriminating between proliferating/undifferentiated non-proliferating/differentiated neurons. Thus, it can be promising tool isolate discover targets intervention.