title: Harmine hydrochloride inhibits Akt phosphorylation and depletes the pool of cancer stem-like cells of glioblastoma.
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.
authors: Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, People's Republic of China.
authors: Huailei
authors: H
authors: Liu
authors: Dayong
authors: D
authors: Han
authors: Yaohua
authors: Y
authors: Liu
authors: Xu
authors: X
authors: Hou
authors: Jianing
authors: J
authors: Wu
authors: Huadong
authors: H
authors: Li
authors: Jie
authors: J
authors: Yang
authors: Chen
authors: C
authors: Shen
authors: Guang
authors: G
authors: Yang
authors: Changyu
authors: C
authors: Fu
authors: Xianfeng
authors: X
authors: Li
authors: Hui
authors: H
authors: Che
authors: Jing
authors: J
authors: Ai
authors: Shiguang
authors: S
authors: Zhao
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002867:Chromones / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000473:pathology*; D006247:Harmine / Q000494:pharmacology*; D006801:Humans; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009025:Morpholines / Q000494:pharmacology; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D002867:Chromones; D004791:Enzyme Inhibitors; C549075:LY 290042; D008996:Monoamine Oxidase Inhibitors; D009025:Morpholines; D009419:Nerve Tissue Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D006247:Harmine; D051058:Oncogene Protein v-akt
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