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Abstract Title:

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

Abstract Source:

J Med Food. 2004 Summer;7(2):157-61. PMID: 20940707

Abstract Author(s):

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

Article Affiliation:

[1] Molecular OncoSurgery, University of Heidelberg and German Cancer Research Center, Heidelberg, Germany [2] Department of General Surgery, University of Heidelberg, Heidelberg, Germany.

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 drugs-as 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.

Study Type : Transgenic Animal Study

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Sayer Ji
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