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

LIFE SCIENCES

卷:86

Article

Jung, Young-Hwa¹  Heo, Jeonghoon¹  Lee, Yong J.²  Kwon, Taeg Kyu³  Kim, Young-Ho¹ 

[1] Kosin Univ, Coll Med, Dept Mol Biol & Immunol, Pusan 602703, South Korea

[2] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA 15213 USA

[3] Keimyung Univ, Sch Med, Dept Immunol, Taegu 700712, South Korea

关键词: Quercetin;    Death receptor 5;    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL);    Apoptosis;   

DOI  :  10.1016/j.lfs.2010.01.008

来源: Elsevier

【 摘 要 】

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 (ADPribose) 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. (C) 2010 Elsevier Inc. All rights reserved.

【 授权许可】

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