Harmine hydrochloride inhibits Akt phosphorylation and depletes the pool of cancer stem-like cells of glioblastoma

Huailei Liu; Dayong Han; Yaohua Liu; Xu Hou; Jianing Wu; Huadong Li; Jie Yang; Chen Shen; Guang Yang; Changyu Fu; Xianfeng Li; Hui Che; Jing Ai; Shiguang Zhao

doi:10.1007/s11060-012-1034-x

Harmine hydrochloride inhibits Akt phosphorylation and depletes the pool of cancer stem-like cells of glioblastoma

J Neurooncol. 2013 Mar;112(1):39-48. doi: 10.1007/s11060-012-1034-x. Epub 2013 Feb 8.

Authors

Huailei Liu¹, Dayong Han, Yaohua Liu, Xu Hou, Jianing Wu, Huadong Li, Jie Yang, Chen Shen, Guang Yang, Changyu Fu, Xianfeng Li, Hui Che, Jing Ai, Shiguang Zhao

Affiliation

¹ Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, People's Republic of China.

PMID: 23392846
DOI: 10.1007/s11060-012-1034-x

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Analysis of Variance
Animals
Apoptosis / drug effects
Brain / drug effects
Brain / pathology
Cell Differentiation / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects*
Chromones / pharmacology
Dose-Response Relationship, Drug
Enzyme Inhibitors / pharmacology
Gene Expression Regulation, Neoplastic / drug effects
Glioblastoma / pathology*
Harmine / pharmacology*
Humans
Monoamine Oxidase Inhibitors / pharmacology*
Morpholines / pharmacology
Neoplastic Stem Cells / drug effects*
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

Substances

Chromones
Enzyme Inhibitors
LY 290042
Monoamine Oxidase Inhibitors
Morpholines
Nerve Tissue Proteins
Proto-Oncogene Proteins c-bcl-2
bcl-2-Associated X Protein
Harmine
Oncogene Protein v-akt