Journal of Molecular Medicine

, Volume 90, Issue 3, pp 309–319 | Cite as

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

  • Kyoung-jin Min
  • Ji Hoon Jang
  • Jung Tae Lee
  • Kyeong Sook Choi
  • Taeg Kyu KwonEmail author
Original Article


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.


RU486 TRAIL Death receptor c-FLIP(L) Bcl-2 



This work was supported by a grant of the Korean Health Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A100711).

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Kyoung-jin Min
    • 1
  • Ji Hoon Jang
    • 1
  • Jung Tae Lee
    • 1
  • Kyeong Sook Choi
    • 2
  • Taeg Kyu Kwon
    • 1
    Email author
  1. 1.Department of Immunology, School of MedicineKeimyung UniversityDaeguSouth Korea
  2. 2.Department of Molecular Science and Technology, Institute for Medical SciencesAjou University School of MedicineSuwonSouth Korea

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