Quercetin nanoparticles induced autophagy and apoptosis through AKT/ERK/Caspase-3 signaling pathway in human neuroglioma cells: In vitro and in vivo

Abstract

Neuroglioma is a complex neuroglial tumor involving dysregulation of many biological pathways at multiple levels. Quercetin is a potent cancer therapeutic agent presented in fruit and vegetables, preventing tumor proliferation, and is a well known cancer therapeutic agent and autophagy mediator. Recent studies showed that drug delivery by nanoparticles have enhanced efficacy with reduced side effects. In this regard, gold-quercetin into poly (dl-lactide-co-glycolide) nanoparticles was examined. In the present study, quercetin nanoparticle induced cell autophagy and apoptosis in human neuroglioma cell was investigated. Quercetin nanoparticle administrated to animals displayed suppressed role in tumor growth. The cell viability was deterined through CCK8 assay. Transmission electron microscopy was utilized to observe the formation of autophagosome. The cell apoptosis was assessed by annexin V-PI staining. The protein expression of cell autophagy regulators and tumor suppressors were analyzed via western blot and RT-PCR. Treatment of human neuroglioma cell with quercetin nanoparticle induced cell death in a dose-and time-dependent manner. The flow cytometry results showed that the proportion of the apoptosis cells had gained after quercetin nanoparticle treatment compared to untreatment group. Moreover, the expression of activated PI3K/AKT and Bcl-2 were down-regulated upon quercetin nanoparticle treatment in human neuroglioma cells. The expression level of LC3 and ERK as well as cytoplasm p53, cleaved Caspase-3 and PARP was positively correlated with the concentration of quercetin nanoparticle. In addition, p-mTOR and GAIP were obviously down-regulated by quercetin nanoparticle treatment in a dose-dependent manner. These results indicated that quercetin nanoparticle could induce autophagy and apoptosis in human neuroglioma cells, the underlying molecular mechanisms, at least partly, through activation LC3/ERK/Caspase-3 and suppression AKT/mTOR signaling.

Keywords: Apoptosis; Autophagy; Neuroglioma; Quercetin nanoparticle.