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 5–25% 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
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