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@ARTICLE{Labsch:127875,
      author       = {S. Labsch$^*$ and L. Liu$^*$ and N. Bauer$^*$ and Y.
                      Zhang$^*$ and E. Aleksandrowicz$^*$ and J. Gladkich$^*$ and
                      F. Schönsiegel$^*$ and I. Herr$^*$},
      title        = {{S}ulforaphane and {TRAIL} induce a synergistic elimination
                      of advanced prostate cancer stem-like cells.},
      journal      = {International journal of oncology},
      volume       = {44},
      number       = {5},
      issn         = {1791-2423},
      address      = {Athens},
      publisher    = {Spandidos Publ.},
      reportid     = {DKFZ-2017-03897},
      pages        = {1470 - 1480},
      year         = {2014},
      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.},
      keywords     = {Antineoplastic Agents (NLM Chemicals) / Isothiocyanates
                      (NLM Chemicals) / TNF-Related Apoptosis-Inducing Ligand (NLM
                      Chemicals) / Protein-Serine-Threonine Kinases (NLM
                      Chemicals) / NF-kappa B kinase (NLM Chemicals) / sulforafan
                      (NLM Chemicals)},
      cin          = {G403},
      ddc          = {610},
      cid          = {I:(DE-He78)G403-20160331},
      pnm          = {317 - Translational cancer research (POF3-317)},
      pid          = {G:(DE-HGF)POF3-317},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:24626333},
      pmc          = {pmc:PMC4027950},
      doi          = {10.3892/ijo.2014.2335},
      url          = {https://inrepo02.dkfz.de/record/127875},
}