title: Oleuropein inhibits the proliferation and invasion of glioma cells via suppression of the AKT signaling pathway.
abstract: 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.
authors: Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, Shandong 250012, P.R. China.
authors: Ming
authors: M
authors: Liu
authors: Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, Shandong 250012, P.R. China.
authors: Jian
authors: J
authors: Wang
authors: Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, Shandong 250012, P.R. China.
authors: Bin
authors: B
authors: Huang
authors: Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, Shandong 250012, P.R. China.
authors: Anjing
authors: A
authors: Chen
authors: Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, Shandong 250012, P.R. China.
authors: Xingang
authors: X
authors: Li
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D005434:Flow Cytometry; D005910:Glioma / Q000473:pathology*; D006801:Humans; D057888:Iridoid Glucosides; D039823:Iridoids / Q000494:pharmacology*; D009361:Neoplasm Invasiveness / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D057888:Iridoid Glucosides; D039823:Iridoids; C002769:oleuropein; D051057:Proto-Oncogene Proteins c-akt