Cancer Chemotherapy and Pharmacology

, Volume 67, Issue 5, pp 1167–1178 | Cite as

Sulforaphane potentiates oxaliplatin-induced cell growth inhibition in colorectal cancer cells via induction of different modes of cell death

  • Bettina M. Kaminski
  • Andreas Weigert
  • Bernhard Brüne
  • Marco Schumacher
  • Uwe Wenzel
  • Dieter Steinhilber
  • Jürgen Stein
  • Sandra UlrichEmail author
Original Article


The objective of this study was to investigate, whether the plant-derived isothiocyanate Sulforaphane (SFN) enhances the antitumor activities of the chemotherapeutic agent oxaliplatin (Ox) in a cell culture model of colorectal cancer. Caco-2 cells were cultured under standard conditions and treated with increasing concentrations of SFN [1–20 μM] and/or Ox [100 nM–10 μM]. For co-incubation, cells were pre-treated with SFN for 24 h. Cell growth was determined by BrdU incorporation. Drug interactions were assessed using the combination-index method (CI) (Cl < 1 indicates synergism). Apoptotic events were characterized by different ELISA techniques. Protein levels were examined by Western blot analysis. Annexin V- and propidium iodide (PI) staining followed by FACS analysis was used to differentiate between apoptotic and necrotic events. SFN and Ox alone inhibited cell growth of Caco-2 cells in a dose-dependent manner, an effect, which could be synergistically enhanced, when cells were incubated with the combination of both agents. Co-treated cells further displayed distinctive morphological changes that occurred during the apoptotic process, such as cell surface exposure of phosphatidylserine, membrane blebbing as well as the occurence of cytoplasmic histone-associated DNA fragments. Further observations thereby pointed toward simultaneous activation of both extrinsic and intrinsic apoptotic pathways. With increasing concentrations and treatment duration, a shift from apoptotic to necrotic cell death could be observed. In conclusion, the data suggest that the isothiocyanate SFN sensitizes colon cancer cells to Ox-induced cell growth inhibition via induction of different modes of cell death.


Sulforaphane Oxaliplatin Colorectal cancer Cell growth Apoptosis 



Colorectal cancer








Combination index


Half maximal inhibitory concentration


Fetal calf serum


Dulbecco’s modified Eagle’s medium


Ethylendiaminetetraacetic acid






TNF-related apoptosis-inducing ligand


Poly [ADP-ribose] polymerase


Propidium Iodide


Fluorescein Isothiocyanate



This work was supported by a graduate scholarship grant from the DFG to Bettina M. Kaminski. Bettina M. Kaminski is a member of the Frankfurt International Research Graduate School for Translational Biomedicine (FIRST), Frankfurt am Main.


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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Bettina M. Kaminski
    • 1
  • Andreas Weigert
    • 3
  • Bernhard Brüne
    • 3
  • Marco Schumacher
    • 4
  • Uwe Wenzel
    • 4
  • Dieter Steinhilber
    • 1
  • Jürgen Stein
    • 1
    • 2
  • Sandra Ulrich
    • 1
    Email author
  1. 1.Institute of Pharmaceutical ChemistryBiozentrum, Goethe UniversityFrankfurt am MainGermany
  2. 2.Department of Internal MedicineKatharina Kasper HospitalFrankfurt am MainGermany
  3. 3.Institute of Biochemistry I/ZAFESGoethe UniversityFrankfurt am MainGermany
  4. 4.Molecular Nutrition Research, Interdisciplinary Research CenterJustus-Liebig-UniversityGiessenGermany

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