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.
Highlights
The naturally occurring compound 6-(methylsulfinyl)hexyl isothiocyanate (6-MITC) was isolated from Wasabia japonica, a pungent spice used in Japanese food worldwide
We evaluated the effects of wasabi compound 6-MITC and its chemical derivatives on human pancreatic cancer cells, the cancer stem cells (CSC) population, and signaling molecules
Cell cycle analysis revealed an increase in percentage of G2/M phase in PANC-1 cells from 22.4 ± 0.8% of controls to 50.4 ± 2.2% of 6-MITC-treated group and 55.8 ± 0.6% of I7557-treated group at 20 μM (Figure 3)
Summary
The naturally occurring compound 6-(methylsulfinyl)hexyl isothiocyanate (6-MITC) was isolated from Wasabia japonica (wasabi), a pungent spice used in Japanese food worldwide. Several signal transduction pathways involve the development and survival of CSC, such as Sonic hedgehog (SHH) [8], NOTCH1 [9], OCT4 [10], Wnt/beta-catenin [11], drug transporters [12], Bmi [13], and SOX2 [14]. Targeting these CSCrelated signaling pathways to augment cancer control has been extensively investigated [15]
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