Sulforaphane enhances irradiation effects in terms of perturbed cell cycle progression and increased DNA damage in pancreatic cancer cells

PLoS One. 2017 Jul 10;12(7):e0180940. doi: 10.1371/journal.pone.0180940. eCollection 2017.

Abstract

Background: Sulforaphane (SFN), an herbal isothiocyanate enriched in cruciferous vegetables like broccoli and cauliflower, has gained popularity for its antitumor effects in cell lines such as pancreatic cancer. Antiproliferative as well as radiosensitizing properties were reported for head and neck cancer but little is known about its effects in pancreatic cancer cells in combination with irradiation (RT).

Methods: In four established pancreatic cancer cell lines we investigated clonogenic survival, analyzed cell cycle distribution and compared DNA damage via flow cytometry and western blot after treatment with SFN and RT.

Results: Both SFN and RT show a strong and dose dependent survival reduction in clonogenic assays, an induction of a G2/M cell cycle arrest and an increase in γH2AX protein level indicating DNA damage. Effects were more pronounced in combined treatment and both cell cycle perturbation and DNA damage persisted for a longer period than after SFN or RT alone. Moreover, SFN induced a loss of DNA repair proteins Ku 70, Ku 80 and XRCC4.

Conclusion: Our results suggest that combination of SFN and RT exerts a more distinct DNA damage and growth inhibition than each treatment alone. SFN seems to be a viable option to improve treatment efficacy of chemoradiation with hopefully higher rates of secondary resectability after neoadjuvant treatment for pancreatic cancer.

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis / radiation effects*
  • Blotting, Western
  • Cell Cycle / drug effects*
  • Cell Cycle / radiation effects*
  • Cell Division / drug effects
  • Cell Division / radiation effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / radiation effects
  • DNA Damage / drug effects*
  • DNA Damage / radiation effects*
  • Flow Cytometry
  • Humans
  • Isothiocyanates / pharmacology*
  • Pancreatic Neoplasms / metabolism
  • Sulfoxides

Substances

  • Isothiocyanates
  • Sulfoxides
  • sulforaphane

Grants and funding

The authors received no specific funding for this work.