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

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Affiliated Author(s)
권택규
Alternative Author(s)
Kwon, Taeg Kyu
Journal Title
Cancer Research
ISSN
0008-5472
Issued Date
2007
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.
Department
Dept. of Immunology (면역학)
Publisher
School of Medicine
Citation
Yong-gyu Son et al. (2007). Silibinin Sensitizes Human Glioma Cells to TRAIL-Mediated Apoptosis via DR5 Up-regulation and Down-regulation of c-FLIP and Survivin. Cancer Research, 67(17), 8274–8284. doi: 10.1158/0008-5472.CAN-07-0407
Type
Article
ISSN
0008-5472
DOI
10.1158/0008-5472.CAN-07-0407
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/35335
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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