Abstract：
:Malignant gliomas are the most common and most aggressive primary brain tumor, and for which differentiation therapy has emerged as a promising candidate strategy. In this study, we used in vitro and in vivo assays to examine the differentiation effects of wogonin, a major active constituent of Scutellaria baicalensis, on glioma C6 and U251 cells. We found that wogonin can suppress cell proliferation and induce G0/G1 arrest under a concentration-dependent manner. Wogonin also triggered significant reduction in the G1 cell-cycle regulatory proteins cyclin D1, cyclin-dependent kinase 2 and 4 along with overexpression of cell-cycle inhibitory proteins p27. Immunofluorescence and western blot analysis indicated that wogonin increased the expression of lineage-specific differentiation marker glial fibrillary acidic protein (GFAP). In mechanisms, we verified that wogonin significantly diminished the phosphorylated level of protein kinase B (AKT), and maintenance of low β-catenin expression level was dependent on glycogen synthase kinase 3β (GSK3β) activation at Ser9. Blocking GSK3β/β-catenin pathway was required for wogonin-induced proliferation inhibition and terminal differentiation by using canonical activator lithium chloride (LiCl) and inhibitor dickkopf-1 (Dkk1). Moreover, intravenous administration of wogonin delayed the growth of C6 glioma in the intracranial tumor model. These findings provide the evidence and mechanistic support for wogonin-based differentiation therapies for malignant glioblastoma. Furthermore, inhibition of GSK3β/β-catenin pathway may be a key and requisite factor in glioma differentiation.
journal_name
Toxicol Lettjournal_title
Toxicology lettersauthors
Wang Y,Zhang Y,Qian C,Cai M,Li Y,Li Z,You Q,Wang Q,Hu R,Guo Qdoi
10.1016/j.toxlet.2013.07.013subject
Has Abstractpub_date
2013-10-24 00:00:00pages
212-23issue
2eissn
0378-4274issn
1879-3169pii
S0378-4274(13)01137-5journal_volume
222pub_type
杂志文章abstract：:Toluene, an industrial organic solvent, is voluntarily inhaled as drug of abuse. Because inhibition of N-methyl-d-aspartate (NMDA) receptors is one of the possible mechanisms underlying developmental neurotoxicity of toluene, the purpose of the present study was to examine the effects of toluene exposure during two ma...
journal_title：Toxicology letters
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journal_title：Toxicology letters
pub_type： 杂志文章,评审
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journal_title：Toxicology letters
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journal_title：Toxicology letters
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journal_title：Toxicology letters
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journal_title：Toxicology letters
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更新日期：2000-03-15 00:00:00
