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: Yoko Fuke, Madoka Hishinuma, Mayumi Namikawa, Yoshie Oishi, Takeshi Matsuzaki
• Journal: Nutrition and cancer (Nutr Cancer) Vol. 66 Issue 5 Pg. 879-87 ( 2014) ISSN: 1532-7914 [Electronic] United States
• PMID: 24895898 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

• 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, metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphorylation
• Plant Extracts (pharmacology)
• Signal Transduction
• Wasabia (chemistry)