PMID- 20096292
OWN - NLM
STAT- MEDLINE
DCOM- 20100318
LR  - 20220318
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Print)
IS  - 0024-3205 (Linking)
VI  - 86
IP  - 9-10
DP  - 2010 Feb 27
TI  - Quercetin enhances TRAIL-induced apoptosis in prostate cancer cells via increased 
      protein stability of death receptor 5.
PG  - 351-7
LID - 10.1016/j.lfs.2010.01.008 [doi]
AB  - AIMS: Quercetin has been shown to enhance tumor necrosis factor-related 
      apoptosis-inducing ligand (TRAIL)-induced apoptosis of prostate cancer cells via 
      mechanisms that include upregulation of death receptor (DR) 5, a protein reported 
      to play an important role in sensitizing cancer cells to apoptosis. We aimed to 
      determine the specific mechanisms underlying quercetin-induced DR5 expression. 
      MAIN METHODS: Human prostate cancer cells were exposed to quercetin and TRAIL. 
      Trypan blue assays and terminal transferase dUTP nick-end labeling (TUNEL) assays 
      evaluated changes in TRAIL resistance after quercetin treatment, and flow 
      cytometry examined quercetin-induced death receptor expression in DU-145 cells. 
      Western blotting, reverse transcription-polymerase chain reaction (RT-PCR) and 
      transiently transfection were utilized to confirm apoptotic patterns of prostate 
      cancer cells. KEY FINDINGS: After stimulation with quercetin, DU-145 cells 
      exhibited stronger sensitization to TRAIL. Quercetin treatment enhanced 
      TRAIL-induced activation proteins in the caspase pathway, such as poly 
      (ADP-ribose) polymerase (PARP), caspase-3, and caspase-9. Quercetin 
      dose-dependently increased DR5 levels in prostate cancer cells, which was 
      mediated by increased transcription and protein stability, but not mRNA 
      stability. Ectopic expression of DR5 dose-dependently increased TRAIL-induced 
      apoptosis. SIGNIFICANCE: Our results showed that the role of quercetin and TRAIL 
      combination therapy may provide a novel strategy for treating prostate cancer by 
      overcoming critical mechanisms of apoptosis resistance.
CI  - Copyright 2009 Elsevier Inc. All rights reserved.
FAU - Jung, Young-Hwa
AU  - Jung YH
AD  - Department of Molecular Biology and Immunology, College of Medicine, Kosin 
      University, Busan 602-703, Korea.
FAU - Heo, Jeonghoon
AU  - Heo J
FAU - Lee, Yong J
AU  - Lee YJ
FAU - Kwon, Taeg Kyu
AU  - Kwon TK
FAU - Kim, Young-Ho
AU  - Kim YH
LA  - eng
GR  - R01 CA140554/CA/NCI NIH HHS/United States
GR  - R01 CA140554-01A1/CA/NCI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100121
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (TNF-Related Apoptosis-Inducing Ligand)
RN  - 9IKM0I5T1E (Quercetin)
SB  - IM
MH  - Apoptosis/*drug effects/physiology
MH  - Cell Line, Tumor
MH  - Humans
MH  - Male
MH  - *Prostatic Neoplasms/drug therapy/metabolism/pathology
MH  - Protein Stability/drug effects
MH  - Quercetin/*pharmacology/therapeutic use
MH  - Receptors, TNF-Related Apoptosis-Inducing Ligand/*chemistry/physiology
MH  - TNF-Related Apoptosis-Inducing Ligand/*physiology/therapeutic use
MH  - Up-Regulation/drug effects/physiology
PMC - PMC3003259
MID - NIHMS257616
COIS- Conflict of interest statement The authors declare no competing financial 
      interests.
EDAT- 2010/01/26 06:00
MHDA- 2010/03/20 06:00
PMCR- 2011/01/01
CRDT- 2010/01/26 06:00
PHST- 2009/11/25 00:00 [received]
PHST- 2010/01/06 00:00 [revised]
PHST- 2010/01/10 00:00 [accepted]
PHST- 2010/01/26 06:00 [entrez]
PHST- 2010/01/26 06:00 [pubmed]
PHST- 2010/03/20 06:00 [medline]
PHST- 2011/01/01 00:00 [pmc-release]
AID - S0024-3205(10)00026-3 [pii]
AID - 10.1016/j.lfs.2010.01.008 [doi]
PST - ppublish
SO  - Life Sci. 2010 Feb 27;86(9-10):351-7. doi: 10.1016/j.lfs.2010.01.008. Epub 2010 
      Jan 21.