Department of Radiation Oncology, Mackay Memorial Hospital, Taipei 104, Taiwan ; Institute of Traditional Medicine, School of Medicine, National Yang Ming University, Taipei 112, Taiwan.
Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan ; School of Chinese Medicine, China Medical University, Taichung 404, Taiwan.
Evid Based Complement Alternat Med. 2014;2014:494739. doi: 10.1155/2014/494739. Epub 2014 Jan 20.
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.
天然存在的化合物 6-(甲硫亚磺酰基)己基异硫氰酸酯（6-MITC）从日本辣根（Wasabi）中分离出来，日本辣根是一种在全球范围内用于日本料理的辛辣香料。合成衍生物 6-(甲硫基)己基异硫氰酸酯（I7447）和 6-(甲磺酰基)己基异硫氰酸酯（I7557）是从小分子化合物 6-MITC 衍生而来。本研究旨在评估这些化合物对人胰腺癌细胞的影响。人胰腺癌细胞系 PANC-1 和 BxPC-3 用于进行 MTT 法细胞活力测定和刘氏染色观察形态。通过 DNA 直方图分析细胞周期。醛脱氢酶（ALDH）活性被用作癌症干细胞（CSC）的标志物。通过 Western blot 法检测与 CSC 信号相关的蛋白表达。结果表明，化合物 6-MITC 和 I7557 但不是 I7447 抑制了 PANC-1 和 BxPC-3 细胞的活力。形态学观察显示 6-MITC 和 I7557 处理的细胞有有丝分裂阻滞和凋亡。这两种化合物诱导 G2/M 期阻滞和亚倍体群体。6-MITC 和 I7557 处理后，PANC-1 细胞中 ALDH 阳性细胞的比例明显降低。CSC 信号分子 SOX2 的表达被 6-MITC 和 I7557 抑制，但 NOTCH1、ABCG2、Sonic hedgehog 或 OCT4 的表达不受抑制。结论：日本辣根化合物 6-MITC 和 I7557 可能具有抑制人胰腺癌细胞生长和 CSC 表型的活性。
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