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

• Verfasst von: Kallifatidis, Georgios [VerfasserIn]
• Verfasst von: Labsch, Sabrina Daniela [VerfasserIn]
• Verfasst von: Rausch, Vanessa [VerfasserIn]
• Verfasst von: Mattern, Jürgen [VerfasserIn]
• Verfasst von: Gladkich, Jury [VerfasserIn]
• Verfasst von: Moldenhauer, Gerhard [VerfasserIn]
• Verfasst von: Büchler, Markus W. [VerfasserIn]
• Verfasst von: Salnikov, Alexey V. [VerfasserIn]
• Verfasst von: Herr, Ingrid [VerfasserIn]
• Titel: Sulforaphane increases drug-mediated cytotoxicity toward cancer stem-like cells of pancreas and prostate
• Verf.angabe: Georgios Kallifatidis, Sabrina Labsch, Vanessa Rausch, Juergen Mattern, Jury Gladkich, Gerhard Moldenhauer, Markus W. Büchler, Alexei V. Salnikov and Ingrid Herr
• Jahr: 2011
• Umfang: 8 S.
• Fussnoten: Published online12 October 2010 ; Gesehen am 07.07.2022
• Titel Quelle: Enthalten in: Molecular therapy
• Ort Quelle: Amsterdam : Elsevier, 2000
• Jahr Quelle: 2011
• Band/Heft Quelle: 19(2011), 1, Seite 188-195
• ISSN Quelle: 1525-0024
• DOI: doi:10.1038/mt.2010.216
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 180940634X

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.