Open Access

The dietary flavonol fisetin enhances the apoptosis-inducing potential of TRAIL in prostate cancer cells

  • Authors: Ewelina Szliszka, Krzysztof J. Helewski, Elzbieta Mizgala, Wojciech Krol
  • View Affiliations

  • Published online on: Wednesday, July 6, 2011
  • Pages: 771-779
  • DOI: 10.3892/ijo.2011.1116

Abstract

Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is an endogenous agent that induces apoptosis selectively in cancer cells. Soluble or expressed in immune cells, TRAIL plays an important role in the defense against tumour cells. The resistance of cancer cells to TRAIL immune surveillance is implicated in tumour development. Naturally occurring flavonoids can sensitize TRAIL-resistant cancer cells and augment their apoptotic activity. Fisetin, a dietary flavonol has cancer preventive properties. This study was designed to investigate the effect of fisetin on the TRAIL-induced apoptosis potential in prostate cancer cells. Prostate cancer cell lines represent an ideal model for research in chemoprevention. Cytotoxicity was measured by MTT and LDH assays. Apoptosis was detected using Αnnexin V-FITC by flow cytometry and fluorescence microscopy. Mito­chondrial membrane potential (ΔΨm) was evaluated using DePsipher staining by fluorescence microscopy. Death receptor (TRAIL-R1 and TRAIL-R2) expression was analysed by flow cytometry. Inhibition of NF-κB (p65) activation was confirmed with an ELISA-based TransAM NF-κB kit. Caspase-8 and caspase-3 activities were determined by colorimetric protease assays. Our study demonstrates that fisetin sensitizes the TRAIL-resistant androgen-dependent LNCaP and the androgen-independent DU145 and PC3 prostate cancer cells to TRAIL-induced death. Fisetin augmented TRAIL-mediated cytotoxicity and apoptosis in prostate cancer LNCaP cells by engaging the extrinsic (receptor-mediated) and intrinsic (mitochondrial) apoptotic pathways. Fisetin increased the expression of TRAIL-R1 and decreased the activity of NF-κB. Co-treatment of cancer cells with TRAIL and fisetin caused significant activation of caspase-8 and caspase-3 and disruption of ΔΨm. Our data indicate the usefulness of fisetin in prostate cancer chemoprevention through enhancement of TRAIL-mediated apoptosis.
Journal Cover

October 2011
Volume 39 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

2012 Impact Factor: 2.657
Ranked #31/196 Oncology
(total number of cites)

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APA
Szliszka, E., Helewski, K., Mizgala, E., & Krol, W. (2011). The dietary flavonol fisetin enhances the apoptosis-inducing potential of TRAIL in prostate cancer cells. International Journal of Oncology, 39(4), 771-779.
MLA
Szliszka, Helewski, Mizgala, and Wojciech Krol. "The dietary flavonol fisetin enhances the apoptosis-inducing potential of TRAIL in prostate cancer cells." International Journal of Oncology International Journal of Oncology 39.4 (2011): 771-779.
Chicago
Szliszka, Helewski, Mizgala, and Wojciech Krol. "The dietary flavonol fisetin enhances the apoptosis-inducing potential of TRAIL in prostate cancer cells." International Journal of Oncology International Journal of Oncology 39 no. 4 (2011): 771-779.