Open Access

Sulforaphane and TRAIL induce a synergistic elimination of advanced prostate cancer stem-like cells

  • Authors:
    • Sabrina Labsch
    • Li Liu
    • Nathalie Bauer
    • Yiyao Zhang
    • Ewa Aleksandrowicz
    • Jury Gladkich
    • Frank Schönsiegel
    • Ingrid Herr
  • View Affiliations

  • Published online on: March 10, 2014     https://doi.org/10.3892/ijo.2014.2335
  • Pages: 1470-1480
  • Copyright: © Labsch et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Advanced androgen-independent prostate cancer (AIPC) is an aggressive malignancy with a poor prognosis. Apoptosis-resistant cancer stem cells (CSCs) have been identified in AIPC and are not eliminated by current therapeutics. Novel therapeutic options, which are currently being evaluated in patient studies, include TRAIL and the broccoli-derived isothiocyanate sulforaphane. Although neither agent targets normal cells, TRAIL induces apoptosis in most cancer cells, and sulforaphane eliminates CSCs. In this study, the established AIPC cell lines DU145 and PC3, with enriched CSC features, and primary patient-derived prostate CSCs were treated with sulforaphane and recombinant soluble TRAIL. We examined the effects of these drugs on NF-κB activity, self-renewal and differentiation potential, and stem cell signaling via spheroid- and colony-forming assays, FACS and western blot analyses, immunohistochemistry, and an antibody protein array in vitro and after xenotransplantation. We largely found a stronger effect of sulforaphane on CSC properties compared to TRAIL, though the agents acted synergistically when applied in combination. This was associated with the inhibition of TRAIL-induced NF-κB binding; CXCR4, Jagged1, Notch 1, SOX 2, and Nanog expression; ALDH1 activity inhibition; and the elimination of differentiation and self-renewal potential. In vivo, tumor engraftment and tumor growth were strongly inhibited, without the induction of liver necrosis or other obvious side effects. These findings suggest that sulforaphane shifts the balance from TRAIL-induced survival signals to apoptosis and thus explains the observed synergistic effect. A nutritional strategy for high sulforaphane intake may target the cancer-specific activity of TRAIL in CSCs.
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May-2014
Volume 44 Issue 5

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

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Spandidos Publications style
Labsch S, Liu L, Bauer N, Zhang Y, Aleksandrowicz E, Gladkich J, Schönsiegel F and Herr I: Sulforaphane and TRAIL induce a synergistic elimination of advanced prostate cancer stem-like cells. Int J Oncol 44: 1470-1480, 2014.
APA
Labsch, S., Liu, L., Bauer, N., Zhang, Y., Aleksandrowicz, E., Gladkich, J. ... Herr, I. (2014). Sulforaphane and TRAIL induce a synergistic elimination of advanced prostate cancer stem-like cells. International Journal of Oncology, 44, 1470-1480. https://doi.org/10.3892/ijo.2014.2335
MLA
Labsch, S., Liu, L., Bauer, N., Zhang, Y., Aleksandrowicz, E., Gladkich, J., Schönsiegel, F., Herr, I."Sulforaphane and TRAIL induce a synergistic elimination of advanced prostate cancer stem-like cells". International Journal of Oncology 44.5 (2014): 1470-1480.
Chicago
Labsch, S., Liu, L., Bauer, N., Zhang, Y., Aleksandrowicz, E., Gladkich, J., Schönsiegel, F., Herr, I."Sulforaphane and TRAIL induce a synergistic elimination of advanced prostate cancer stem-like cells". International Journal of Oncology 44, no. 5 (2014): 1470-1480. https://doi.org/10.3892/ijo.2014.2335