6-(Methylsulfinyl)hexyl isothiocyanate (6-MSITC), a major bioactive compound in Wasabi [Wasabia japonica (Miq.) Matsum.], has revealed the inhibitory effect on colon
carcinogenesis in rat
cancer model although the underlying mechanism is unclear. In this study, we used two types of human
colorectal cancer cells (HCT116 p53+/+ and HCT116 p53-/- ) to investigate the anticancer activity and molecular mechanisms of 6-MSITC. Interestingly, 6-MSITC inhibited the cell proliferation in both types of cells with similar IC50 value although a light increase in the phosphorylation and accumulation of P53
protein was observed in HCT116 p53+/+ cells at 24 h
after treatment. In addition, 6-MSITC increased the ratio of proapoptotic cells in both types of cells with the same fashion in a p53-independent manner. The data from mitochondrial analysis revealed that 6-MSITC enhanced the ratio of proapoptotic B-cell lymphoma-2-associated X
protein/antiapoptotic myeloid cell
leukemia 1, and sequentially caused mitochondrial membrane potential (ΔΨm ) loss,
cytochrome c release, and
caspase-3 activation in both types of cells. Taken together, Wasabi 6-MSITC induced apoptosis of human
colorectal cancer cells in p53-independent
mitochondrial dysfunction pathway. These findings suggest that 6-MSITC might be a potential agent for
colon cancer chemoprevention although with p53 mutation. © 2018 BioFactors, 2018.