Sulforaphane increases drug-mediated cytotoxicity toward cancer stem-like cells of pancreas and prostate

Georgios Kallifatidis, Sabrina Labsch, Vanessa Rausch, Juergen Mattern, Jury Gladkich, Gerhard Moldenhauer, Markus W. Büchler, Alexei V. Salnikov, Ingrid Herr

Research output: Contribution to journalArticle

140 Scopus citations

Abstract

Despite intense efforts to develop treatments against pancreatic cancer, agents that cure this highly resistant and metastasizing disease are not available. Considerable attention has focused on broccoli compound sulforaphane (SF), which is suggested as combination therapy for targeting of pancreatic cancer stem cells (CSCs). However, there are concerns that antioxidative properties of SF may interfere with cytotoxic drugsas suggested, e.g., for vitamins. Therefore we investigated a combination therapy using established pancreatic CSCs. Although cisplatin (CIS), gemcitabine (GEM), doxorubicin, 5-flurouracil, or SF effectively induced apoptosis and prevented viability, combination of a drug with SF increased toxicity. Similarly, SF potentiated the drug effect in established prostate CSCs revealing that SF enhances drug cytotoxicity also in other tumor entities. Most importantly, combined treatment intensified inhibition of clonogenicity and spheroid formation and aldehyde dehydrogenase 1 (ALDH1) activity along with Notch-1 and c-Rel expression indicating that CSC characteristics are targeted. In vivo, combination treatment was most effective and totally abolished growth of CSC xenografts and tumor-initiating potential. No pronounced side effects were observed in normal cells or mice. Our data suggest that SF increases the effectiveness of various cytotoxic drugs against CSCs without inducing additional toxicity in mice.

Original languageEnglish (US)
Pages (from-to)188-195
Number of pages8
JournalMolecular Therapy
Volume19
Issue number1
DOIs
StatePublished - Jan 2011

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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    Kallifatidis, G., Labsch, S., Rausch, V., Mattern, J., Gladkich, J., Moldenhauer, G., Büchler, M. W., Salnikov, A. V., & Herr, I. (2011). Sulforaphane increases drug-mediated cytotoxicity toward cancer stem-like cells of pancreas and prostate. Molecular Therapy, 19(1), 188-195. https://doi.org/10.1038/mt.2010.216