Wasabi-Derived 6-(Methylsulfinyl)Hexyl Isothiocyanate Induces Apoptosis in Human Breast Cancer by Possible Involvement of the NF-κB Pathways

• Published in: Nutrition and cancer Vol. 66; no. 5; pp. 879 - 887
• Main Authors: Fuke, Yoko, Hishinuma, Madoka, Namikawa, Mayumi, Oishi, Yoshie, Matsuzaki, Takeshi
• Format: Journal Article
• Language: English
• Published: United States Routledge 2014
• Subjects: Animals; Antineoplastic Agents - pharmacology; apoptosis; Apoptosis - drug effects; bioactive properties; Breast Neoplasms; Caspase 3 - metabolism; Caspase 7 - metabolism; caspases; Cell Line, Tumor; DNA; DNA fragmentation; DNA Fragmentation - drug effects; drugs; Female; Humans; ingredients; Inhibitory Concentration 50; Isothiocyanates - pharmacology; Japan; MCF-7 Cells; melanoma; Mice; Mice, Inbred BALB C; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; nutrition; oral administration; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Plant Extracts - pharmacology; Signal Transduction; spices; transcription factor NF-kappa B; Wasabia - chemistry; Wasabia japonica; Japan
• ISSN: 1532-7914; 0163-5581; 1532-7914
• DOI: 10.1080/01635581.2014.916322

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.