Silibinin Sensitizes Human Glioma Cells to TRAIL-Mediated Apoptosis via DR5 Up-regulation and Down-regulation of c-FLIP and Survivin

Authors
Yong-gyu SonEun Hee KimJin Yeop KimSeung U. KimTaeg Kyu KwonA-Rum YoonChae-Ok YunKyeong Sook Choi
Department
Dept. of Immunology (면역학)
Issue Date
2007
Citation
Cancer Research, Vol.67(17) : 8274-8284, 2007
ISSN
0008-5472
Abstract
Silibinin, a flavonoid isolated from Silybum marianum, has been reported to have cancer chemopreventive and therapeutic effects. Here, we show that treatment with subtoxic doses of silibinin in combination with tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) induces rapid apoptosis in TRAIL-resistant glioma cells, but not in human astrocytes, suggesting that this combined treatment may offer an attractive strategy for safely treating gliomas. Although the proteolytic processing of procaspase-3 by TRAIL was partially blocked in glioma cells, cotreatment with silibinin efficiently recovered TRAIL-induced caspase activation in these cells. Silibinin treatment up-regulated DR5, a death receptor of TRAIL, in a transcription factor CHOP-dependent manner. Furthermore, treatment with silibinin down-regulated the protein levels of the antiapoptotic proteins FLIPL, FLIPS, and survivin through proteasome-mediated degradation. Taken together, our results show that the activity of silibinin to modulate multiple components in the death receptor–mediated apoptotic pathway is responsible for its ability to recover TRAIL sensitivity in TRAIL-resistant glioma cells.
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/35335
Appears in Collections:
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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