Abstract:
: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.
journal_name
Cancer Lettjournal_title
Cancer lettersauthors
Dixit D,Ghildiyal R,Anto NP,Ghosh S,Sharma V,Sen Edoi
10.1016/j.canlet.2013.03.025subject
Has Abstractpub_date
2013-08-19 00:00:00pages
347-58issue
2eissn
0304-3835issn
1872-7980pii
S0304-3835(13)00255-3journal_volume
336pub_type
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