Synergy between broccoli sprout extract and selenium in the upregulation of thioredoxin reductase in human hepatocytes

Dietary isothiocyanates and selenium (Se) can up-regulate thioredoxin reductase 1 (TR1) in cultured human HepG2 and MCF-7 cells [Zhang et al. (2003). Synergy between sulforaphane and selenium in the induction of thioredoxin reductase 1 requires both transcriptional and translational modulation. Carcinogenesis, 24, 497–503; Wang et al. (2005). Sulforaphane, erucin and iberin up-regulate thioredoxin reductase expression in human MCF-7 cells. Journal of Agricultural and Food Chemistry, 53, 1417–1421] at both the protein and mRNA levels. In this study, broccoli sprout extract (a rich source of the isothiocyanates sulforaphane and iberin) and Se interacted synergistically to induce TR1 in immortalised human hepatocytes. Broccoli sprout extracts containing 1.6, 4 and 8 μM isothiocyanates were tested for their ability to induce TR1 at the protein and mRNA level. Although induction of TR1 mRNA by broccoli sprout extract (1.6–8 μM) was only 1.7–2.2-fold, co-treatment with Se (0.2–1 μM) enhanced the expression of TR1 mRNA (3.0–3.3-fold). Moreover, broccoli sprout extract induced the cellular concentration of TR1 and TR enzymatic activity, an induction that was augmented by Se addition. Thus, broccoli sprout extract (8 μM) and Se induced cellular TR1 concentration and enzymatic activity 3.7- and 5-fold respectively, whereas, Se or broccoli sprout extract alone produced an induction of only approximately 2-fold. These data suggest that dietary isothiocyanates from broccoli sprouts and Se are important agents in the regulation of redox status in human liver cells. The synergistic effect between isothiocyanates and Se at physiologically-relevant concentrations on the induction of TR1 may play an important role in protection against oxidative stress.