| Hispidulin potently inhibits human glioblastoma multiforme cells through activation of AMP-activated protein kinase (AMPK). | |
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MedLine Citation:
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PMID: 20698539 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Glioblastoma multiforme (GBM) is the most common and lethal type of primary brain tumor. Despite recent therapeutic advances in other cancers, the treatment of GBM remains ineffective and essentially palliative. The current focus lies in the finding of components that activate the AMP-activated protein kinase (AMPK), one key enzyme thought to be activated during the caloric restriction (CR). In the present study, we found that treatment of hispidulin, a flavone isolated from Saussurea involucrate Kar. et Kir., resulted in dose-dependent inhibition of GBM cellular proliferation. Interestingly, we show that hispidulin activated AMPK in GBM cells. The 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 mRNA translation. Moreover, hispidulin-activated AMPK decreases the activity and/or expression of lipogenic enzymes, such as fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACC). Furthermore, hispidulin blocked the progression of the cell cycle at the G1 phase and induced apoptosis by inducing p53 expression and further upregulating p21 expression in GBM cells. On the basis of these results, we demonstrated that hispidulin has the potential to be a chemopreventive and therapeutic agent against human GBM. |
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Authors:
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Ying-Chao Lin; Chao-Ming Hung; Jia-Chun Tsai; Jang-Chang Lee; Yi-Lin Sophia Chen; Chyou-Wei Wei; Jung-Yie Kao; Tzong-Der Way |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of agricultural and food chemistry Volume: 58 ISSN: 1520-5118 ISO Abbreviation: J. Agric. Food Chem. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-09-02 Completed Date: 2010-12-10 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0374755 Medline TA: J Agric Food Chem Country: United States |
Other Details:
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Languages: eng Pagination: 9511-7 Citation Subset: IM |
Affiliation:
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Institute of Biochemistry, College of Life Science, National Chung Hsing University, Taichung, Taiwan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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drug effects Brain Neoplasms / enzymology, pathology* Cell Division / drug effects Cell Line, Tumor Enzyme Activation Flavones / pharmacology* Glioblastoma / enzymology, pathology* Humans Proto-Oncogene Proteins c-akt / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Flavones; 1447-88-7/hispidulin; EC 2.7.11.1/Proto-Oncogene Proteins c-akt |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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