Sulforaphane induces DNA double strand breaks predominantly repaired by homologous recombination pathway in human cancer cells

Biochem Biophys Res Commun. 2008 Dec 12;377(2):341-345. doi: 10.1016/j.bbrc.2008.09.150. Epub 2008 Oct 12.

Abstract

Cytotoxicity and DNA double strand breaks (DSBs) were studied in HeLa cells treated with sulforaphane (SFN), a well-known chemo-preventive agent. Cell survival was impaired by SFN in a concentration and treatment time-dependent manner. Both constant field gel electrophoresis (CFGE) and gamma-H2AX assay unambiguously indicated formation of DSBs by SFN, reflecting the cell survival data. These DSBs were predominantly processed by homologous recombination repair (HRR), judging from the SFN concentration-dependent manner of Rad51 foci formation. On the other hand, the phosphorylation of DNA-PKcs, a key non-homologous end joining (NHEJ) protein, was not observed by SFN treatment, suggesting that NHEJ may not be involved in DSBs induced by this chemical. G2/M arrest by SFN, a typical response for cells exposed to ionizing radiation was also observed. Our new data indicate the clear induction of DSBs by SFN and a useful anti-tumor aspect of SFN through the induction of DNA DSBs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticarcinogenic Agents / pharmacology*
  • Cell Division / drug effects
  • Cell Division / genetics
  • Cell Survival / drug effects*
  • DNA Breaks, Double-Stranded*
  • DNA Repair
  • DNA, Neoplasm / drug effects*
  • DNA, Neoplasm / genetics
  • G2 Phase / drug effects
  • G2 Phase / genetics
  • HeLa Cells
  • Histones / metabolism
  • Humans
  • Isothiocyanates
  • Recombination, Genetic
  • Sulfoxides
  • Thiocyanates / pharmacology*

Substances

  • Anticarcinogenic Agents
  • DNA, Neoplasm
  • H2AX protein, human
  • Histones
  • Isothiocyanates
  • Sulfoxides
  • Thiocyanates
  • sulforaphane