PMID- 22846543 OWN - NLM STAT- MEDLINE DCOM- 20130109 LR - 20220409 IS - 1873-3913 (Electronic) IS - 0898-6568 (Linking) VI - 24 IP - 11 DP - 2012 Nov TI - Wogonin induces apoptosis by activating the AMPK and p53 signaling pathways in human glioblastoma cells. PG - 2216-25 LID - 10.1016/j.cellsig.2012.07.019 [doi] AB - 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. CI - Copyright (c) 2012 Elsevier Inc. All rights reserved. FAU - Lee, Dae-Hee AU - Lee DH AD - Department of Neurosurgery, University of Virginia, School of Medicine, VA, USA. FAU - Lee, Tae Hwa AU - Lee TH FAU - Jung, Chang Hwa AU - Jung CH FAU - Kim, Young-Ho AU - Kim YH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120728 PL - England TA - Cell Signal JT - Cellular signalling JID - 8904683 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Cell Cycle Proteins) RN - 0 (Drugs, Chinese Herbal) RN - 0 (EIF4EBP1 protein, human) RN - 0 (Flavanones) RN - 0 (Phosphoproteins) RN - 0 (Reactive Oxygen Species) RN - 0 (Tumor Suppressor Protein p53) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) RN - EC 3.4.22.- (Caspases) RN - EC 6.4.1.2 (Acetyl-CoA Carboxylase) RN - POK93PO28W (wogonin) SB - IM MH - AMP-Activated Protein Kinases/*metabolism MH - Acetyl-CoA Carboxylase/metabolism MH - Adaptor Proteins, Signal Transducing/metabolism MH - Apoptosis/*drug effects MH - Caspases/metabolism MH - Cell Cycle Proteins MH - Cell Line, Tumor MH - DNA Damage/drug effects MH - Drugs, Chinese Herbal MH - Flavanones/*pharmacology MH - Glioblastoma/metabolism/pathology MH - Humans MH - Phosphoproteins/metabolism MH - Reactive Oxygen Species/metabolism MH - Signal Transduction/*drug effects MH - TOR Serine-Threonine Kinases/metabolism MH - Tumor Suppressor Protein p53/*metabolism EDAT- 2012/08/01 06:00 MHDA- 2013/01/10 06:00 CRDT- 2012/08/01 06:00 PHST- 2012/05/18 00:00 [received] PHST- 2012/07/10 00:00 [revised] PHST- 2012/07/24 00:00 [accepted] PHST- 2012/08/01 06:00 [entrez] PHST- 2012/08/01 06:00 [pubmed] PHST- 2013/01/10 06:00 [medline] AID - S0898-6568(12)00215-X [pii] AID - 10.1016/j.cellsig.2012.07.019 [doi] PST - ppublish SO - Cell Signal. 2012 Nov;24(11):2216-25. doi: 10.1016/j.cellsig.2012.07.019. Epub 2012 Jul 28.