Differential Pharmacological Activities of Oxygen Numbers on the Sulfoxide Moiety of Wasabi Compound 6-(Methylsulfinyl) Hexyl Isothiocyanate in Human Oral Cancer Cells

Molecules. 2018 Sep 21;23(10):2427. doi: 10.3390/molecules23102427.


6-(methylsulfinyl) hexyl isothiocyanate (6-MITC) is a naturally occurring compound isolated from Wasabia japonica (wasabi). The synthetic derivatives, 6-(methylsulfenyl) hexyl isothiocyanate (I7447) and 6-(methylsulfonyl) hexyl isothiocyanate (I7557), were derived from 6-MITC with the deletion and addition of oxygen, respectively. We aimed to evaluate the effect of these synthetic compounds on human oral cancer cells, SAS and OECM-1. All three compounds (I7447, 6-MITC, and I7557) inhibited the viability of SAS and OECM-1 cells using MTT assay. Morphological observations showed various proportions of mitotic arrest and apoptosis in cells treated with these compounds. Cell cycle analysis revealed relatively abundant G2/M arrest in 6-MITC and I7557-treated cells, whereas sub-G1 accumulation was found in I7447-treated cells. In using phosphorylated histone H3 as a marker for mitosis, the addition of 6-MITC and I7557 (excluding I7447) could be shown to arrest cells during mitosis. In contrast, I7447 induced more prominent apoptosis than the 6-MITC or I7557 compounds. The down-regulated expression of the phosphorylated form of CHK1 and Cdc25c was noted in 6-MITC and I7557-treated cells. I7557 could sensitize SAS cells to death by radiation. The wasabi compound, 6-MITC, and its chemical derivatives with different numbers of oxygen may have differential pharmacological effects on human oral cancer cells.

Keywords: 6-MITC; I7447; I7557; apoptosis; mitosis; oral cancer; wasabi.

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Checkpoint Kinase 1 / metabolism*
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic / drug effects
  • Histones / metabolism
  • Humans
  • Isothiocyanates / chemical synthesis*
  • Isothiocyanates / chemistry
  • Isothiocyanates / pharmacology
  • Mouth Neoplasms / drug therapy
  • Mouth Neoplasms / metabolism*
  • Oxygen / chemistry
  • Phosphorylation
  • Plant Extracts / chemistry
  • Wasabia / chemistry*
  • cdc25 Phosphatases / metabolism*


  • 6-(Methylsulfinyl)hexyl isothiocyanate
  • Antineoplastic Agents
  • Histones
  • Isothiocyanates
  • Plant Extracts
  • CHEK1 protein, human
  • Checkpoint Kinase 1
  • CDC25C protein, human
  • cdc25 Phosphatases
  • Oxygen