title: Wasabi-derived 6-(methylsulfinyl)hexyl isothiocyanate induces apoptosis in human breast cancer by possible involvement of the NF-κB pathways.
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.
authors.affiliation: a Department of Health Promotion Sciences, Graduate School of Human Health Sciences , Tokyo Metropolitan University , Hachioji-shi , Tokyo , Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Fuke
authors.forename: Madoka
authors.initials: M
authors.lastname: Hishinuma
authors.forename: Mayumi
authors.initials: M
authors.lastname: Namikawa
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Oishi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsuzaki
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D045744:Cell Line, Tumor; D053938:DNA Fragmentation / Q000187:drug effects; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D017879:Isothiocyanates / Q000494:pharmacology*; D007564:Japan; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology; D015398:Signal Transduction; D031228:Wasabia / Q000737:chemistry
chemical_list: C505386:6-(Methylsulfinyl)hexyl isothiocyanate; D000970:Antineoplastic Agents; D017879:Isothiocyanates; D016328:NF-kappa B; D010936:Plant Extracts; D019869:Phosphatidylinositol 3-Kinases; C505407:CASP3 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053179:Caspase 7