Epigenetic impact of dietary isothiocyanates in cancer chemoprevention.

OBJECTIVE

There is growing evidence that cancer chemopreventive agents including isothiocyanates (ITCs) from cruciferous vegetables target epigenetic mechanisms. The present report will summarize novel findings of ITCs on histone deacetylase activity, DNA methylation, and short noncoding microRNAs, focusing on sulforaphane (SFN) from broccoli and phenethylisothiocyanate from watercress.

RESULTS

In a human intervention study, broccoli sprouts led to more efficient histone deacetylase inhibition in blood cells than a broccoli sprout supplement, correlating with higher levels of urinary ITC metabolites. A proteomics study with ¹⁴C-labeled ITCs revealed among others a direct interaction with histones and chromatin-modulating proteins. The well investigated Kelch-like erythroid-cell-derived protein with CNC homology-associated protein 1/nuclear factor erythroid 2-related factor 2/antioxidant-response element pathway is both affected by and mechanistically involved in epigenetic activities of ITCs. Accordingly, reduction of oxidative stress is shown to prevent hypertension-associated global hypomethylation in rats. Combination of SFN with (-)-epigallocatechin gallate as a demethylating agent is identified as an effective approach for re-expression of estrogen receptor in hormone negative breast cancer. Induction of miR-200c by SFN prevents epithelial-mesenchymal-transition and could be relevant for prevention of metastases.

CONCLUSIONS

The last year has identified interesting areas of ITCs affecting epigenetic mechanisms that will have implications for translational cancer (prevention) research once validated in animal studies and human intervention studies.