Isothiocyanates, membrane-permeable electrophiles that form adducts with thiol, have been suggested to have important medical benefits. 6- (Methylsulfinyl) hexyl isothiocyanate (6-HITC) , the major isothiocyanate compound in
wasabi, has been identified as an inducer of detoxification enzymes in rat liver epithelial RL34 cells. We have reported that the expression level of genes encoding detoxification enzymes in human intestinal Caco-2 cells is regulated by the enterocyte differentiation process. The present study was conducted to evaluate the effect of 6-HITC on proliferating and differentiated Caco-2 cells exposed to a wide variety of orally-ingested compounds including chemoprotective compounds. Treatment with 6-HITC decreased the level of proteasome activity in proliferating Caco-2 cells and induced HO-1 expression in those that had undifferentiated and differentiated. Proteasome inhibition with MG132 also induced HO-1 expression in proliferating Caco-2 cells, but not in those that had differentiated. These results indicate that 6-HITC induces HO-1 gene expression via a distinct pathway that differs between the proliferation and differentiation stages in Caco-2 cells.
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