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

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.

• Authors: Young-Hwa Jung, Jeonghoon Heo, Yong J Lee, Taeg Kyu Kwon, Young-Ho Kim
• Journal: Life sciences (Life Sci) Vol. 86 Issue 9-10 Pg. 351-7 (Feb 27 2010) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 20096292 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2009 Elsevier Inc. All rights reserved.

Chemical References

• Receptors, TNF-Related Apoptosis-Inducing Ligand
• TNF-Related Apoptosis-Inducing Ligand
• Quercetin

Topics

• Apoptosis (drug effects, physiology)
• Cell Line, Tumor
• Humans
• Male
• Prostatic Neoplasms (drug therapy, metabolism, pathology)
• Protein Stability (drug effects)
• Quercetin (pharmacology, therapeutic use)
• Receptors, TNF-Related Apoptosis-Inducing Ligand (chemistry, physiology)
• TNF-Related Apoptosis-Inducing Ligand (physiology, therapeutic use)
• Up-Regulation (drug effects, physiology)