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Quercetin enhances TRAIL-induced apoptosis in prostate cancer cells via increased protein stability of death receptor 5

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Author(s)
Young-Hwa JungJeonghoon HeoYong J. LeeTaeg Kyu KwonYoung-Ho Kim
Keimyung Author(s)
Kwon, Taeg Kyu
Department
Dept. of Immunology (면역학)
Journal Title
Life Science
Issued Date
2010
Volume
86
Issue
Issues 9-10
Keyword
QuercetinDeath receptor 5Tumor necrosis factor-relatedapoptosis-inducing ligand (TRAIL)Apoptosis
Abstract
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.

Keywords
Quercetin;
Death receptor 5;
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL);
Apoptosis
Keimyung Author(s)(Kor)
권택규
Publisher
School of Medicine
Citation
Young-Hwa Jung et al. (2010). Quercetin enhances TRAIL-induced apoptosis in prostate cancer cells via increased protein stability of death receptor 5. Life Science, 86(Issues 9-10), 351–357. doi: 10.1016/j.lfs.2010.01.008
Type
Article
ISSN
0024-3205
DOI
10.1016/j.lfs.2010.01.008
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/36306
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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