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Nutr Cancer ; 66(5): 879-87, 2014.
Article in English | MEDLINE | ID: mdl-24895898

ABSTRACT

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.


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