Hydroxytyrosol's effect on the expression of apoptosis and oxidative stress related genes in BE (2)-C neuroblastoma cell line

Abstract

Neuroblastoma (NB) is defined as a type of tumor that involves the autonomic nervous system. Oxidative stress (OxS) resulted from dopamine (DA) oxidation and the reduction of antioxidant enzyme activity is the main reason for the initiation and progression of NB. The aim of this study was the evaluation of the protective effects of Hydroxytyrosol (HT) against OxS induced by H2O2. In the present in vitro study, the OxS condition was induced by H2O2 treatment of BE (2)-C cells; then, the cells were treated by several concentrations of HT and Vitamin C (VC). Next, the expression levels of genes related to OxS and apoptosis were measured through the RT-qPCR method. Subsequently, the activity of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) was determined via enzyme colorimetric assay. Finally, the level of malondialdehyde (MDA) was measured by the Thiobarbituric acid reactive substances (TBARS) assay. HT treatment leads to a significantly decreased the expression level of Bax, caspase-3, and p53 (p < 0.05); as well, the expression levels of Nrf-2, SOD, Bcl-2, PPAR-γ, CAT, and GPx were increased at a significant manner (p < 0.05). Moreover, HT treatment led to a remarkable increase in the enzyme activity of CAT, SOD, and GPx (p < 0.001). Finally, the MDA levels were significantly reduced (p < 0.001) in BE (2)-C cells after HT treatment. The findings suggest that HT could have neuroprotective effects by enhancing various enzymatic and molecular pathways to increase the cellular antioxidant defense. Additionally, HT reduced the expression of the P53 gene and blocked the apoptotic signaling pathways by suppressing Bax and caspase-3. However, further animal models studies are needed to approve the beneficial effects of HT.