Harmine hydrochloride inhibits Akt phosphorylation and depletes the pool of cancer stem-like cells of glioblastoma
Harmine hydrochloride inhibits Akt phosphorylation and depletes the pool of cancer stem-like cells of glioblastoma
复制标题
盐酸去氢骆驼蓬碱抑制 Akt 磷酸化并消耗胶质母细胞瘤的癌症干细胞样细胞库
DOI：
10.1007/s11060-012-1034-x
复制
发表时间：
2013-03-01
影响因子：
3.9
通讯作者：
Zhao, Shiguang
中科院分区：
文献类型：
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作者：
Liu, Huailei;Han, Dayong;Zhao, Shiguang
盐酸毒碱（Harmine hydrochloride, Har-hc）是一种从植物中提取的天然毒碱衍生物，已被认为可用于治疗多种癌症和脑病。在本研究中，我们发现Har-hc明显降低胶质母细胞瘤细胞系细胞活力，诱导细胞凋亡，抑制Akt磷酸化。此外，Har-hc具有抑制胶质母细胞瘤干细胞样细胞（GSLCs）自我更新和促进分化的能力，同时抑制Akt磷酸化。特别是，我们证明了Har-hc抑制人原代GSLCs的神经球形成。体内实验也证实了Har-hc能降低GSLCs的致瘤性。因此，我们得出结论，Har-hc对胶质母细胞瘤细胞具有强大的抗癌作用，至少部分是通过抑制Akt磷酸化来实现的。给药Har-hc可能成为治疗胶质母细胞瘤的新途径。
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.