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

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Jung YH, Heo J, Lee YJ, Kwon TK, Kim YH

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

Life Sci. 2010 Feb 27;86(9-10):351-7. doi: 10.1016/j.lfs.2010.01.008. Epub 2010 Jan 21.

PubMed ID
20096292 [ View in PubMed
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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.