PMID- 24002210
OWN - NLM
STAT- MEDLINE
DCOM- 20140407
LR  - 20220331
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Linking)
VI  - 30
IP  - 5
DP  - 2013 Nov
TI  - Ibuprofen enhances TRAIL-induced apoptosis through DR5 upregulation.
PG  - 2379-84
LID - 10.3892/or.2013.2713 [doi]
AB  - Numerous human chemoprevention studies have demonstrated that non-steroidal 
      anti-inflammatory drugs (NSAIDs) possess chemopreventive effects against a 
      variety of malignant tumors. However, there have been many clinical studies on 
      aspirin, but not ibuprofen, even though ibuprofen is one of the most clinically 
      and safely used NSAIDs showing potent anti-inflammatory effects. Moreover, we 
      reported that many chemopreventive agents enhance the apoptosis-inducing effects 
      of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which is 
      known to be crucial for cancer prevention. We, therefore, investigated whether 
      ibuprofen enhances the cytocidal effect of TRAIL and found that ibuprofen 
      markedly stimulated the apoptosis-inducing efficacy of TRAIL against human colon 
      cancer HCT116 cells. As detected by western blot analysis and real-time RT-PCR, 
      ibuprofen upregulated the expression of death receptor 5 (DR5), a TRAIL receptor. 
      TRAIL-induced apoptosis enhanced by ibuprofen was effectively decreased by a 
      caspase inhibitor and dominant-negative DR5. Noteworthy, co-treatment of 
      ibuprofen with TRAIL did not enhance apoptosis in normal peripheral blood 
      mononuclear cells (PBMCs). These results demonstrated that ibuprofen and TRAIL 
      synergistically induced apoptosis in human colon cancer HCT116 cells but not in 
      normal PBMCs, raising the possibility that ibuprofen may be promising as a safe 
      chemopreventive agent against colon cancer.
FAU - Todo, Momoko
AU  - Todo M
AD  - Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical 
      Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, 
      Kamigyo-ku, Kyoto 602-8566, Japan.
FAU - Horinaka, Mano
AU  - Horinaka M
FAU - Tomosugi, Mitsuhiro
AU  - Tomosugi M
FAU - Tanaka, Ryoichi
AU  - Tanaka R
FAU - Ikawa, Haruna
AU  - Ikawa H
FAU - Sowa, Yoshihiro
AU  - Sowa Y
FAU - Ishikawa, Hideki
AU  - Ishikawa H
FAU - Fujiwara, Hitoshi
AU  - Fujiwara H
FAU - Otsuji, Eigo
AU  - Otsuji E
FAU - Sakai, Toshiyuki
AU  - Sakai T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130830
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (TNFSF10 protein, human)
RN  - WK2XYI10QM (Ibuprofen)
SB  - IM
MH  - Apoptosis/drug effects
MH  - Colonic Neoplasms/*genetics/pathology
MH  - Drug Synergism
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - HCT116 Cells
MH  - Humans
MH  - Ibuprofen/*administration & dosage
MH  - Receptors, TNF-Related Apoptosis-Inducing Ligand/*biosynthesis/metabolism
MH  - TNF-Related Apoptosis-Inducing Ligand/*genetics/metabolism
MH  - Up-Regulation/drug effects
EDAT- 2013/09/05 06:00
MHDA- 2014/04/08 06:00
CRDT- 2013/09/05 06:00
PHST- 2013/06/25 00:00 [received]
PHST- 2013/07/29 00:00 [accepted]
PHST- 2013/09/05 06:00 [entrez]
PHST- 2013/09/05 06:00 [pubmed]
PHST- 2014/04/08 06:00 [medline]
AID - 10.3892/or.2013.2713 [doi]
PST - ppublish
SO  - Oncol Rep. 2013 Nov;30(5):2379-84. doi: 10.3892/or.2013.2713. Epub 2013 Aug 30.