oleuropein and Glioma

Brain tumorigenesis has been associated not only with oxidative stress, but also with a reduced response of non-enzyme and enzyme antioxidant defense systems. In fact, the imbalance between free-radical production and the efficiency of the antioxidant defense systems triggers the process because the central nervous system (CNS) is very sensitive to free-radical damage. Phenolic compounds, mainly oleuropein and its major metabolite hydroxytyrosol, derived from olives and virgin olive oil, have been shown to exert important anticancer activities both in vitro and in vivo due to their antioxidant properties. The present study analyzes the effects of the oral administration of oleuropein, hydroxytyrosol and the mixture of both phenolic compounds in rats with transplacental N-ethyl-N-nitrosourea (ENU)-induced brain tumors to analyze their potential effect against brain tumorigenesis through the modification of redox system components. Oxidative stress parameters, non-enzyme and enzyme antioxidant defense systems and blood chemistry were assayed in the different experimental groups. The treatment with oleuropein, hydroxytyrosol and/or the mixture of both phenolic compounds promotes a limited beneficial effect as anticancer compounds in our ENU-induced animal model of brain tumor. These effects occur via redox control mechanisms involving endogenous enzymatic and non-enzymatic antioxidant defense systems, and are highly dependent on the gender of the animals.

Topics: Administration, Oral; Animals; Antioxidants; Ethylnitrosourea; Glioma; Iridoid Glucosides; Phenylethyl Alcohol; Rats; Sex Characteristics

Oleuropein, the main phenolic compound of secoiridoids, has been proven to have inhibitory effects on various types of cancers. However, the antitumor effects and related mechanisms in glioma remain unclear. In the present study, U251 and A172 cells were used to assess the effects of oleuropein. Using cell viability assay, we found that oleuropein greatly inhibited the viability of the U251 and A172 cells. Additionally, flow cytometric apoptosis assay indicated that oleuropein induced the apoptosis of the two cell lines. Consistently, the inhibitory effects of oleuropein on migration and invasion were also observed in vitro. In regards to the mechanism, we found that oleuropein significantly decreased phosphorylation of AKT (p-AKT), accompanied by upregulation of Bax and downregulation of Bcl-2. We also found that there was a decrease in the expression levels of matrix metalloproteinase-2 (MMP-2) and MMP-9 after treatment with oleuropein. Furthermore, a specific phosphatidylinositol 3 kinase (PI3K) inhibitor, LY294002, enhanced the pro-apoptotic and anti-invasive effects induced by oleuropein, which suggested that oleuropein suppressed the growth and invasion of glioma cells via inhibition of AKT activity. Taken together, our results indicated that treatment with oleuropein may be an effective therapy for malignant glioma through suppression of tumor proliferation and invasion by inhibition of the AKT signaling pathway.

Topics: Antineoplastic Agents; Apoptosis; Blotting, Western; Brain Neoplasms; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Survival; Flow Cytometry; Glioma; Humans; Iridoid Glucosides; Iridoids; Neoplasm Invasiveness; Proto-Oncogene Proteins c-akt; Signal Transduction