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Harmine hydrochloride inhibits Akt phosphorylation and depletes the pool of cancer stem-like cells of glioblastoma.
- Source :
-
Journal of neuro-oncology [J Neurooncol] 2013 Mar; Vol. 112 (1), pp. 39-48. Date of Electronic Publication: 2013 Feb 08. - Publication Year :
- 2013
-
Abstract
- Harmine hydrochloride (Har-hc), a derivative from Harmine which is a natural extractive from plants, has been considered for treatment of kinds of cancers and cerebral diseases. In this study, we found that Har-hc clearly decreased cell viability, induced apoptosis and inhibited Akt phosphorylation in glioblastoma cell lines. Moreover, Har-hc had the ability to inhibit self-renewal and promote differentiation of glioblastoma stem like cells (GSLCs) accompanied by inhibition of Akt phosphorylation. Especially, we demonstrated that Har-hc inhibited neurosphere formation of human primary GSLCs. In vivo test also confirmed Har-hc decreased the tumorigenicity of GSLCs. Thus we conclude that Har-hc has potent anti-cancer effects in glioblastoma cells, which is at least partially via inhibition of Akt phosphorylation. Administration of Har-hc may act as a new approach to glioblastoma treatment.
- Subjects :
- Analysis of Variance
Animals
Apoptosis drug effects
Brain drug effects
Brain pathology
Cell Differentiation drug effects
Cell Line, Tumor
Chromones pharmacology
Dose-Response Relationship, Drug
Enzyme Inhibitors pharmacology
Gene Expression Regulation, Neoplastic drug effects
Humans
Morpholines pharmacology
Neoplastic Stem Cells pathology
Nerve Tissue Proteins metabolism
Oncogene Protein v-akt genetics
Oncogene Protein v-akt metabolism
Phosphorylation drug effects
Proto-Oncogene Proteins c-bcl-2 genetics
Proto-Oncogene Proteins c-bcl-2 metabolism
Signal Transduction
Time Factors
bcl-2-Associated X Protein genetics
bcl-2-Associated X Protein metabolism
Cell Proliferation drug effects
Glioblastoma pathology
Harmine pharmacology
Monoamine Oxidase Inhibitors pharmacology
Neoplastic Stem Cells drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1573-7373
- Volume :
- 112
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of neuro-oncology
- Publication Type :
- Academic Journal
- Accession number :
- 23392846
- Full Text :
- https://doi.org/10.1007/s11060-012-1034-x