%0 Journal Article
%T Effect of Wasabi Component 6-(Methylsulfinyl)hexyl Isothiocyanate and Derivatives on Human Pancreatic Cancer Cells
%A Yu-Jen Chen
%A Yu-Chuen Huang
%A Tung-Hu Tsai
%A Hui-Fen Liao
%J Evidence-Based Complementary and Alternative Medicine
%D 2014
%I Hindawi Publishing Corporation
%R 10.1155/2014/494739
%X 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. 1. Introduction The naturally occurring compound 6-(methylsulfinyl)hexyl isothiocyanate (6-MITC) was isolated from Wasabia japonica (wasabi), a pungent spice used in Japanese food worldwide. This compound has been reported as having anti-inflammatory [1], chemopreventive [2], and antimelanoma [3] activities. The synthetic compounds derived from 6-MITC include 6-(methylsulfenyl)hexyl isothiocyanate (I7447) and 6-(methylsulfonyl)hexyl isothiocyanate (I7557). Pancreatic cancer is a malignancy with increasing incidence and has been the fourth leading cause of cancer related death [4]. Due to the difficulty in making an early diagnosis, an unresectable stage at diagnosis in the majority, and resistance to chemotherapy or radiotherapy, the prognosis is poor with a 5-year survival rate of only 5¨C25% even after aggressive treatment [5]. It has been demonstrated that cancer stem cells (CSC) are crucial factors for treatment resistance and metastasis in many types of malignancies, including pancreatic cancer [6, 7]. Several signal transduction pathways involve the development and survival of CSC, such as Sonic
%U http://www.hindawi.com/journals/ecam/2014/494739/