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Glucocorticoid receptor antagonist sensitizes TRAIL-induced apoptosis in renal carcinoma cells through up-regulation of DR5 and down-regulation of c-FLIP(L) and Bcl-2

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Affiliated Author(s)
권택규
Alternative Author(s)
Kwon, Taeg Kyu
Journal Title
Journal of Molecular Medicine
ISSN
0946-2716
Issued Date
2012
Keyword
RU486TRAILDeath receptorc-FLIP(L)Bcl-2
Abstract
RU486 (Mifepristone) has been known as antiprogesterone and antiglucocorticoid agent. RU486 is also used for treatment of several cancers, such as breast, ovarian, prostate, and glaucoma. Here, we investigated the effect of RU486 on TRAIL-induced apoptosis in human renal carcinoma Caki cells. Low dose of RU486 (30–50 μM) alone had no effect on apoptosis, but RU486 markedly sensitized Caki cells to TRAIL-induced apoptosis. We found that up-regulation of death receptor 5 (DR5; receptor for TRAIL ligand), and down-regulation of Bcl-2 and c-FLIP (caspase regulator) contributes to RU-486 induced TRAIL sensitization. Down-regulation of DR5 by siRNA also blocked RU486 induced TRAIL sensitization. Furthermore, overexpression of Bcl-1 or c-FLIP(L) inhibited the cell death induced by the combined treatment with RU486 and TRAIL. RU486 increased DR5 expression at the transcriptional levels through induction of CHOP expression. By contrast, RU486 did not sensitize normal human mesangial cells to TRAIL-mediated apoptosis. Effect of RU486 on TRAIL-induced cancer cell apoptosis was independent of glucocorticoid receptor and progesterone receptor. Taken together, RU486 enhances TRAIL-mediated apoptosis through down-regulation of Bcl-2 and c-FLIP(L) as well as CHOP-mediated DR5 up-regulation.
Department
Dept. of Immunology (면역학)
Publisher
School of Medicine
Citation
Kyoung-jin Min et al. (2012). Glucocorticoid receptor antagonist sensitizes TRAIL-induced apoptosis in renal carcinoma cells through up-regulation of DR5 and down-regulation of c-FLIP(L) and Bcl-2. Journal of Molecular Medicine, 90(3), 309–319. doi: 10.1007/s00109-011-0821-8
Type
Article
ISSN
0946-2716
DOI
10.1007/s00109-011-0821-8
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/34168
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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