Wasabi-derived 6-(methylsulfinyl)hexyl isothiocyanate induces apoptosis in human breast cancer by possible involvement of the NF-κB pathways

Nutr Cancer. 2014;66(5):879-87. doi: 10.1080/01635581.2014.916322. Epub 2014 Jun 4.


6-(methylsulfinyl)hexyl isothiocyanate (6-MSITC) is a bioactive ingredient of wasabi (Wasabia japonica), which is a popular spice in Japan. 6-MSITC has been reported to inhibit the proliferation of breast cancer and melanoma cell lines. We inoculated 30 female Balb-nu/nu mice with MDA-MB-231 or -453 cells, and orally administered varying concentrations of 6-MSITC for 12 days following tumor growth. The tumor volumes and tumor weights from mice inoculated with MDA-MB-231 cells, and the tumor volumes of MDA-MB-453 cells were significantly inhibited by 6-MSITC on Days 9 and 11 after drug administration. DNA fragmentation, DNA ladder, and caspase 3/7 activity performed in vitro revealed that 6-MSITC induced apoptosis of MDA-MB-231, MDA-MB-453, and MCF-7 cells. Furthermore, nuclear factor-κB (NF-κB) expression in the nuclei and phosphorylation of inhibitor κBα (IκBα) was downregulated by 6-MSITC in a concentration-dependent manner; however, this activity was not observed in MCF-7 cells. Moreover, this downregulation of phosphorylated IκBα by 6-MSITC in MDA-MB-231 and -453 cells supports its inhibitory effects on NF-κB activity. The expression of phosphorylated AKT (pAKT) reduced by 6-MSITC was confirmed in MDA-MB-231 cells. Thus, we conclude that 6-MITC promotes apoptosis of breast cancer cells by inhibiting NF-kB and therefore releasing its control of the PI3K/AKT pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Breast Neoplasms
  • Caspase 3 / metabolism
  • Caspase 7 / metabolism
  • Cell Line, Tumor
  • DNA Fragmentation / drug effects
  • Female
  • Humans
  • Inhibitory Concentration 50
  • Isothiocyanates / pharmacology*
  • Japan
  • MCF-7 Cells
  • Mice
  • Mice, Inbred BALB C
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation
  • Plant Extracts / pharmacology
  • Signal Transduction
  • Wasabia / chemistry


  • 6-(Methylsulfinyl)hexyl isothiocyanate
  • Antineoplastic Agents
  • Isothiocyanates
  • NF-kappa B
  • Plant Extracts
  • Phosphatidylinositol 3-Kinases
  • CASP3 protein, human
  • CASP7 protein, human
  • Caspase 3
  • Caspase 7