胶质1
细胞凋亡
癌症研究
胶质瘤
NF-κB
化学
刺猬信号通路
MAPK/ERK通路
干细胞
细胞生物学
信号转导
生物
生物化学
作者
Deobrat Dixit,Ruchi Ghildiyal,Nikhil Ponnoor Anto,Sourav Ghosh,Vivek Sharma,Ellora Sen
出处
期刊:Cancer Letters
[Elsevier]
日期:2013-08-01
卷期号:336 (2): 347-358
被引量:30
标识
DOI:10.1016/j.canlet.2013.03.025
摘要
Since Shh pathway effector, Gli1, is overexpressed in gliomas, we investigated the effect of novel Shh inhibitor SANT-1 on glioma cell viability. Though SANT-1 failed to induce apoptosis, it reduced proliferation of glioma stem-like cells. Apart from canonical Shh cascade, Gli1 is also induced by non-canonical pathways including NFκB. Therefore, a combinatorial strategy with Ras/NFκB inhibitor, Guggulsterone, was employed to enhance effectiveness of SANT-1. Guggulsterone inhibited Ras and NFκB activity and sensitized cells to SANT-1 induced apoptosis via intrinsic apoptotic mechanism. Inhibition of either Ras or NFκB activity was sufficient to sensitize cells to SANT-1. Guggulsterone induced ERK activation also contributed to Caspase-9 activation. Since SANT-1 and Guggulsterone differentially target stem-like and non-stem glioma cells respectively, this combination warrants investigation as an effective anti-glioma therapy.
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