title: Effect of Wasabi Component 6-(Methylsulfinyl)hexyl Isothiocyanate and Derivatives on Human Pancreatic Cancer Cells.
abstract: The naturally occurring compound 6-(methylsulfinyl)hexyl isothiocyanate (6-MITC) was isolated from Wasabia japonica (Wasabi), a pungent spice used in Japanese food worldwide. The synthetic derivatives 6-(methylsulfenyl)hexyl isothiocyanate (I7447) and 6-(methylsulfonyl)hexyl isothiocyanate (I7557) are small molecule compounds derived from 6-MITC. This study aimed to evaluate the effect of these compounds on human pancreatic cancer cells. Human pancreatic cancer cell lines PANC-1 and BxPC-3 were used to perform an MTT assay for cell viability and Liu's stain for morphological observation. The cell cycle was analyzed by DNA histogram. Aldehyde dehydrogenase (ALDH) activity was used as a marker for cancer stem cells (CSC). Western blotting was performed for the expression of proteins related to CSC signaling. The results showed that compounds 6-MITC and I7557, but not I7447, inhibited viability of both PANC-1 and BxPC-3 cells. Morphological observation showed mitotic arrest and apoptosis in 6-MITC- and I7557-treated cells. These two compounds induced G2/M phase arrest and hypoploid population. Percentages of ALDH-positive PANC-1 cells were markedly reduced by 6-MITC and I7557 treatment. The expression of CSC signaling molecule SOX2, but not NOTCH1, ABCG2, Sonic hedgehog, or OCT4, was inhibited by 6-MITC and I7557. In conclusion, wasabi compounds 6-MITC and I7557 may possess activity against the growth and CSC phenotypes of human pancreatic cancer cells.
authors.affiliation: Department of Radiation Oncology, Mackay Memorial Hospital, Taipei 104, Taiwan ; Institute of Traditional Medicine, School of Medicine, National Yang Ming University, Taipei 112, Taiwan.
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan ; School of Chinese Medicine, China Medical University, Taichung 404, Taiwan.
authors.forename: Yu-Chuen
authors.initials: YC
authors.lastname: Huang
authors.affiliation: Institute of Traditional Medicine, School of Medicine, National Yang Ming University, Taipei 112, Taiwan ; Department of Education and Research, Taipei City Hospital, Taipei 103, Taiwan.
authors.forename: Tung-Hu
authors.initials: TH
authors.lastname: Tsai
authors.affiliation: Institute of Traditional Medicine, School of Medicine, National Yang Ming University, Taipei 112, Taiwan ; Department of Biochemical Science and Technology, National Chiayi University, Chiayi 600, Taiwan.
authors.forename: Hui-Fen
authors.identifier: 0000-0001-9060-2176
authors.initials: HF
authors.lastname: Liao