title: Wogonin induces apoptosis by activating the AMPK and p53 signaling pathways in human glioblastoma cells.
abstract: 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.
authors: Department of Neurosurgery, University of Virginia, School of Medicine, VA, USA.
authors: Dae-Hee
authors: DH
authors: Lee
authors: Tae Hwa
authors: TH
authors: Lee
authors: Chang Hwa
authors: CH
authors: Jung
authors: Young-Ho
authors: YH
authors: Kim
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000187:drug effects; D004365:Drugs, Chinese Herbal; D044950:Flavanones / Q000494:pharmacology*; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D010750:Phosphoproteins / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D004365:Drugs, Chinese Herbal; C087000:EIF4EBP1 protein, human; D044950:Flavanones; D010750:Phosphoproteins; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D020169:Caspases; D000103:Acetyl-CoA Carboxylase; C085514:wogonin