PMID- 22008998
OWN - NLM
STAT- MEDLINE
DCOM- 20120705
LR  - 20211020
IS  - 1432-1440 (Electronic)
IS  - 0946-2716 (Linking)
VI  - 90
IP  - 3
DP  - 2012 Mar
TI  - 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.
PG  - 309-19
LID - 10.1007/s00109-011-0821-8 [doi]
AB  - 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 muM) 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.
FAU - Min, Kyoung-Jin
AU  - Min KJ
AD  - Department of Immunology, School of Medicine, Keimyung University, 2800 
      Dalgubeoldaero, Dalseo-Gu, Daegu 704-701, South Korea.
FAU - Jang, Ji Hoon
AU  - Jang JH
FAU - Lee, Jung Tae
AU  - Lee JT
FAU - Choi, Kyeong Sook
AU  - Choi KS
FAU - Kwon, Taeg Kyu
AU  - Kwon TK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111019
PL  - Germany
TA  - J Mol Med (Berl)
JT  - Journal of molecular medicine (Berlin, Germany)
JID - 9504370
RN  - 0 (CASP8 and FADD-Like Apoptosis Regulating Protein)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Receptors, Glucocorticoid)
RN  - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (TNF-Related Apoptosis-Inducing Ligand)
RN  - 147336-12-7 (Transcription Factor CHOP)
RN  - 320T6RNW1F (Mifepristone)
SB  - IM
MH  - Apoptosis/*drug effects
MH  - CASP8 and FADD-Like Apoptosis Regulating Protein/*drug 
      effects/genetics/metabolism
MH  - Carcinoma, Renal Cell/*metabolism/pathology
MH  - Cell Line
MH  - Down-Regulation
MH  - HT29 Cells
MH  - Humans
MH  - Mesangial Cells/metabolism/pathology
MH  - Mifepristone/*pharmacology
MH  - Proto-Oncogene Proteins c-bcl-2/*drug effects/genetics/metabolism
MH  - Receptors, Glucocorticoid/antagonists & inhibitors
MH  - Receptors, TNF-Related Apoptosis-Inducing Ligand/*drug 
      effects/genetics/metabolism
MH  - TNF-Related Apoptosis-Inducing Ligand/*drug effects/metabolism/pharmacology
MH  - Transcription Factor CHOP/*drug effects/genetics/metabolism/pharmacology
MH  - Up-Regulation
EDAT- 2011/10/20 06:00
MHDA- 2012/07/06 06:00
CRDT- 2011/10/20 06:00
PHST- 2011/06/01 00:00 [received]
PHST- 2011/10/07 00:00 [accepted]
PHST- 2011/09/28 00:00 [revised]
PHST- 2011/10/20 06:00 [entrez]
PHST- 2011/10/20 06:00 [pubmed]
PHST- 2012/07/06 06:00 [medline]
AID - 10.1007/s00109-011-0821-8 [doi]
PST - ppublish
SO  - J Mol Med (Berl). 2012 Mar;90(3):309-19. doi: 10.1007/s00109-011-0821-8. Epub 
      2011 Oct 19.