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Hispidulin potently inhibits human glioblastoma multiforme cells through activation of AMP-activated protein kinase (AMPK)
- Source :
- Journal of agricultural and food chemistry. 58(17)
- Publication Year :
- 2010
-
Abstract
- 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.
- Subjects :
- biology
Brain Neoplasms
AMPK
Apoptosis
General Chemistry
Cell cycle
Flavones
Enzyme Activation
Enzyme activator
chemistry.chemical_compound
Biochemistry
AMP-activated protein kinase
chemistry
Eukaryotic initiation factor
Cell Line, Tumor
biology.protein
Cancer research
Hispidulin
Humans
General Agricultural and Biological Sciences
Protein kinase A
Glioblastoma
Proto-Oncogene Proteins c-akt
PI3K/AKT/mTOR pathway
Cell Division
Subjects
Details
- ISSN :
- 15205118
- Volume :
- 58
- Issue :
- 17
- Database :
- OpenAIRE
- Journal :
- Journal of agricultural and food chemistry
- Accession number :
- edsair.doi.dedup.....40066352f41cdd72c9b9f0fb16168ef2