wogonin and Glioblastoma

To explore the effect of wogonin on the proliferation and invasion of glioblastoma U87 cells and its related mechanism.. Glioblastoma U87 cells were cultured in vitro in RPMI1640 medium added with 100 mL/L fetal bovine serum. After cell adherence, the cells were inoculated with 20 μL culture solution (control group), 20 μL wogonin solutions (0, 50 and 100) μmol/L for 48 hours, respectively. The 0 μmol/L wogonin group used 20 μL PBS instead. Cell proliferation was analyzed by MTT assay. The cell invasion ability was detected using Transwell™ invasion assay. The expressions of ezrin mRNA was examined through real-time quantitative PCR. The expressions of ezrin, Bcl-2 and Bax proteins as well as phosphorylated ezrin protein level were measured by Western blotting. Apoptosis index (AI) was determined through terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling (TUNEL) assay.. The inhibitory rate of cell proliferation significantly increased in 50 and 100 μmol/L wogonin groups as compared with 0 μmol/L wogonin group and control group. Moreover, that was higher in 100 μmol/L wogonin group than 50 μmol/L wogonin group. In comparison with control and 0 μmol/L wogonin groups, the mean cell numbers of permeated membrane, levels of ezrin mRNA, ezrin protein and Bcl-2 protein, and phosphorylated ezrin protein level gradually decreased but the level of Bax protein and AI were gradually elevated with the increase of wogonin concentrations; however, there was no significant difference in these indicators between 0 μmol/L wogonin group and control group.. Wogonin could attenuate the proliferation and invasion of wogonin U87 cells, which may be associated with the inhibition of ezrin protein expression and phosphorylation activity and the induction of cell apoptosis.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; bcl-2-Associated X Protein; Cell Line, Tumor; Cell Proliferation; Drugs, Chinese Herbal; Flavanones; Glioblastoma; Humans; Neoplasm Invasiveness; Proto-Oncogene Proteins c-bcl-2

We investigated the molecular basis of the ability of wogonin to control the intracellular signaling cascades of AMP-activated protein kinase (AMPK). This activity induces antitumor activities in glioblastoma multiforme (GBM) cells. Recently, the evolutionarily conserved serine/threonine kinase AMPK has emerged as a possible target for tumor control. We investigated the effects of wogonin on apoptosis regulation and the activation of AMPK. Wogonin treatment resulted in a series of antitumor effects such as cell death and apoptotic appearance. Activation of AMPK suppressed downstream substrates, such as the mammalian target of rapamycin (mTOR) and eukaryotic initiation factor 4E-binding protein-1 (4E-BP1), and resulted in a general decrease in translation. Moreover, wogonin-activated AMPK decreased the activity and/or expression of lipogenic enzymes such as acetyl-CoA carboxylase. Furthermore, in GBM cells, wogonin blocked cell cycle progression at the G1 phase and induced apoptosis by inducing p53 expression and further upregulating p21 expression. Taken together, our findings demonstrated that wogonin has the potential to be a chemopreventive and therapeutic agent against human GBM.

Topics: Acetyl-CoA Carboxylase; Adaptor Proteins, Signal Transducing; AMP-Activated Protein Kinases; Apoptosis; Caspases; Cell Cycle Proteins; Cell Line, Tumor; DNA Damage; Drugs, Chinese Herbal; Flavanones; Glioblastoma; Humans; Phosphoproteins; Reactive Oxygen Species; Signal Transduction; TOR Serine-Threonine Kinases; Tumor Suppressor Protein p53