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

121 Citations (Scopus)

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 1 2011

Fingerprint

Neoplastic Stem Cells
Prostate
Pancreas
Pharmaceutical Preparations
Pancreatic Neoplasms
gemcitabine
Brassica
Drug Combinations
sulforafan
Heterografts
Vitamins
Doxorubicin
Cisplatin
Neoplasms
Prostatic Neoplasms
Apoptosis
Therapeutics
Growth

ASJC Scopus subject areas

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

Cite this

Sulforaphane increases drug-mediated cytotoxicity toward cancer stem-like cells of pancreas and prostate. / Kallifatidis, Georgios; Labsch, Sabrina; Rausch, Vanessa; Mattern, Juergen; Gladkich, Jury; Moldenhauer, Gerhard; Büchler, Markus W.; Salnikov, Alexei V.; Herr, Ingrid.

In: Molecular Therapy, Vol. 19, No. 1, 01.01.2011, p. 188-195.

Research output: Contribution to journalArticle

Kallifatidis, G, Labsch, S, Rausch, V, Mattern, J, Gladkich, J, Moldenhauer, G, Büchler, MW, Salnikov, AV & Herr, I 2011, 'Sulforaphane increases drug-mediated cytotoxicity toward cancer stem-like cells of pancreas and prostate', Molecular Therapy, vol. 19, no. 1, pp. 188-195. https://doi.org/10.1038/mt.2010.216
Kallifatidis, Georgios ; Labsch, Sabrina ; Rausch, Vanessa ; Mattern, Juergen ; Gladkich, Jury ; Moldenhauer, Gerhard ; Büchler, Markus W. ; Salnikov, Alexei V. ; Herr, Ingrid. / Sulforaphane increases drug-mediated cytotoxicity toward cancer stem-like cells of pancreas and prostate. In: Molecular Therapy. 2011 ; Vol. 19, No. 1. pp. 188-195.
@article{94768ee1452643418cd701edb61dc598,
title = "Sulforaphane increases drug-mediated cytotoxicity toward cancer stem-like cells of pancreas and prostate",
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.",
author = "Georgios Kallifatidis and Sabrina Labsch and Vanessa Rausch and Juergen Mattern and Jury Gladkich and Gerhard Moldenhauer and B{\"u}chler, {Markus W.} and Salnikov, {Alexei V.} and Ingrid Herr",
year = "2011",
month = "1",
day = "1",
doi = "10.1038/mt.2010.216",
language = "English (US)",
volume = "19",
pages = "188--195",
journal = "Molecular Therapy",
issn = "1525-0016",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Sulforaphane increases drug-mediated cytotoxicity toward cancer stem-like cells of pancreas and prostate

AU - Kallifatidis, Georgios

AU - Labsch, Sabrina

AU - Rausch, Vanessa

AU - Mattern, Juergen

AU - Gladkich, Jury

AU - Moldenhauer, Gerhard

AU - Büchler, Markus W.

AU - Salnikov, Alexei V.

AU - Herr, Ingrid

PY - 2011/1/1

Y1 - 2011/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=78650901935&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78650901935&partnerID=8YFLogxK

U2 - 10.1038/mt.2010.216

DO - 10.1038/mt.2010.216

M3 - Article

VL - 19

SP - 188

EP - 195

JO - Molecular Therapy

JF - Molecular Therapy

SN - 1525-0016

IS - 1

ER -